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Article ; Online: Ordinal outcomes add value to clinical trials.

Klok, F A / Siegerink, B

2023 Volume 401, Issue 10381, Page(s) 995

MeSH term(s)	Humans ; Stroke/drug therapy ; Research Design
Language	English
Publishing date	2023-03-23
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)00137-X
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Zs.MG 94: Show issues

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Article ; Online: Searching the literature to explain unexpected clinical observations: all that glitters is not gold.

van Mens, T E / Klok, F A / Levi, M

European journal of internal medicine

2023 Volume 112, Page(s) 17–18

Language	English
Publishing date	2023-04-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2023.04.007
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Article ; Online: De valkuil van zoeken op internet.

van Mens, Thijs E / Klok, F A / Levi, Marcel

Nederlands tijdschrift voor geneeskunde

2023 Volume 167

Abstract: When confronted with an unexpected clinical observation, such as a remarkable symptom in a patient with an unrelated rare disease, clinicians increasingly apply online literature search to support the observed correlation. Against a background of an ... ...

Title translation	Pitfalls of searching online: all symptoms, diseases and adverse events appear correlated.
Abstract	When confronted with an unexpected clinical observation, such as a remarkable symptom in a patient with an unrelated rare disease, clinicians increasingly apply online literature search to support the observed correlation. Against a background of an exponential rise in medical publications and the well-documented problem of publication bias, the easy access to literature carries the risk of suggesting spurious correlations. The current paper expounds on this phenomenon. Queries in medical search engines often provide a number of hits, regardless of the plausibility of the correlation searched for. To quantify this, we recently performed a study involving 30.000 automated queries in PubMed using completely random search terms drawn from lists of diseases, symptoms and medications. This provided a background rate of PubMed hits. The data support that several hits by no means automatically indicate a relevant correlation, and underline need for judicious critical appraisal when searching for a correlation observed in daily practice.
MeSH term(s)	Humans ; Rare Diseases ; Internet ; Search Engine
Language	Dutch
Publishing date	2023-11-23
Publishing country	Netherlands
Document type	English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Initial decomposition of floating leaf blades of

Klok, Peter F / van der Velde, Gerard

PeerJ

2023 Volume 11, Page(s) e16689

Abstract: Background: During a study on the outdoor floating leaf blade production of : Methods: Data on initial decomposition over time were collected for all leaves during one growth season in four plots: two in outdoor mesocosms and two in an oxbow lake. ... ...

Abstract	Background: During a study on the outdoor floating leaf blade production of Methods: Data on initial decomposition over time were collected for all leaves during one growth season in four plots: two in outdoor mesocosms and two in an oxbow lake. Each leaf was tagged uniquely upon appearance in a plot. The vegetation in the mesocosms differed with respect to plant species, one contained a monoculture of Results: The observed causes of damage on floating leaves were consumption and/or damage by waterbirds (
MeSH term(s)	Magnoliopsida ; Plant Leaves ; Plants ; Poaceae ; Water
Chemical Substances	Water (059QF0KO0R)
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.16689
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Article ; Online: Wanneer moet je aan een longembolie denken?

Burggraaf-van Delft, J L I / la Roi-Teeuw, Hannah M / de Wit, J / Klok, F A / Cannegieter, S C / Geersing, G J

Nederlands tijdschrift voor geneeskunde

2024 Volume 168

Abstract: Pulmonary embolism (PE) is a common disease, which can present with a variety of symptoms. Optimal use of diagnostics is challenging given the tight and delicate balance between underdiagnosis and over-testing or overdiagnosis. Diagnostic delay occurs in ...

Title translation	When to suspect pulmonary embolism: a balancing act.
Abstract	Pulmonary embolism (PE) is a common disease, which can present with a variety of symptoms. Optimal use of diagnostics is challenging given the tight and delicate balance between underdiagnosis and over-testing or overdiagnosis. Diagnostic delay occurs in a substantial part of patients, and seems more common in those with known cardiopulmonary disease or non-specific signs and symptoms. At the other end of the spectrum, the amount of diagnostic imaging increases. Increased use of diagnostic imaging in general leads to more harmful exposures and might result in overtreatment, as may be the case in subsegmental PE. Correct use of clinical prediction rules reduces the need for diagnostic imaging while PE can still be ruled out safely. This clinical lesson describes three cases of PE and provides an overview of factors that contribute to underdiagnosis or overdiagnosis. We provide recommendations to improve our balancing act for this challenging disease.
MeSH term(s)	Humans ; Pulmonary Embolism/diagnosis ; Female ; Delayed Diagnosis ; Male ; Middle Aged ; Aged
Language	Dutch
Publishing date	2024-04-24
Publishing country	Netherlands
Document type	Journal Article ; Case Reports ; English Abstract
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Anti-Xa-activiteit bij laagmoleculairgewicht heparine.

Klok, F A Erik / den Exter, Paul L / Bosma, Madeleen / Eikenboom, H C J Jeroen

Nederlands tijdschrift voor geneeskunde

2023 Volume 167

Abstract: The anti-factor Xa assay is designed to measure plasma low-molecular-weight heparin (LMWH) levels and to monitor heparin therapy. Notably, the results of anti-factor Xa testing cannot be used in the same way as the International Normalized Ratio (INR) is ...

Title translation	Anti-Xa activity in LMWH treatment: when to assess and what to do with the result.
Abstract	The anti-factor Xa assay is designed to measure plasma low-molecular-weight heparin (LMWH) levels and to monitor heparin therapy. Notably, the results of anti-factor Xa testing cannot be used in the same way as the International Normalized Ratio (INR) is used to guide cumarin treatment: dose adjustments to remain in the therapeutic range have not been shown to be associated with better outcomes of care and lower rates of thrombotic and/or bleeding complications. The anti-factor Xa activity should therefore only be assessed in cases of considerable concern regarding an LWMH under- or overdosis. It is reasonable to lower the LMWH dose in case of a supratherapeutic anti-factor Xa activity. Increasing the LMWH dose in case of a subtherapeutic anti-factor Xa activity should however only be considered in case of morbid obesity or in the setting of breakthrough thrombosis in patients receiving therapeutic dosed LMWH, as long as the anti-factor Xa activity remains below the upper-level of the recommend range.
MeSH term(s)	Humans ; Heparin, Low-Molecular-Weight/therapeutic use ; Anticoagulants/therapeutic use ; Thrombosis/prevention & control ; Obesity, Morbid
Chemical Substances	Heparin, Low-Molecular-Weight ; Anticoagulants
Language	Dutch
Publishing date	2023-07-05
Publishing country	Netherlands
Document type	English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: External validation of AF-BLEED for predicting major bleeding and for tailoring NOAC dose in AF patients: A post hoc analysis in the ENGAGE AF-TIMI 48.

Chu, G / Valerio, L / Barco, S / Huisman, M V / Konstantinides, S V / Klok, F A

Thrombosis research

2023 Volume 229, Page(s) 225–231

Abstract: Objective: AF-BLEED, a simple bleeding risk classifier, was found to predict major bleeding (MB) in patients with atrial fibrillation (AF) and identify AF patients at high risk of MB who might potentially benefit from a lower direct oral anticoagulant ... ...

Abstract	Objective: AF-BLEED, a simple bleeding risk classifier, was found to predict major bleeding (MB) in patients with atrial fibrillation (AF) and identify AF patients at high risk of MB who might potentially benefit from a lower direct oral anticoagulant dose. This post hoc study aimed to externally validate these findings in the ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor Xa next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction study 48) trial. Methods: The ENGAGE AF-TIMI 48 trial randomized AF patients to higher-dose edoxaban regimen (HDER 60/30 mg) versus lower-dose edoxaban regimen (LDER 30/15 mg), with prespecified dose reduction criteria. AF-BLEED was calculated in the modified intention-to-treat cohort (n = 21,026 patients) used for primary outcome analysis. Annualized event rates and hazard ratios (HRs) were obtained for the primary composite outcome (PCO) and its single components (MB, ischemic stroke/systemic embolism and death) to compare LDER 30 mg with HDER 60 mg in both AF-BLEED classes. Results: AF-BLEED classified 2882 patients (13.7 %) as high-risk, characterized by a two- to three-fold higher MB risk than AF-BLEED classified low-risk patients. AF-BLEED classified high-risk patients randomized to LDER 30 mg demonstrated a 3.3 % reduction in MB at the cost of a 0.5 % increase in ischemic stroke/systemic embolism. LDER 30 mg resulted in a 3.1 % reduction of PCO compared to HDER 60 mg (HR of 0.81; 95%CI 0.65-1.01). Additional to existing dose reduction criteria, another 6 % of patients could potentially benefit of this dose adjustment strategy. Conclusion: AF-BLEED could identify AF patients to be at high risk of major bleeding. Our findings support the hypothesis that LDER 30 mg might provide a reasonable option in AF patients with legitimate bleeding concerns.
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.08.001
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Article ; Online: Andexanet alfa: hét antidotum voor factor Xa-remmers?

Klok, F A / Huisman, Menno V

Nederlands tijdschrift voor geneeskunde

2019 Volume 163

Abstract: Andexanet alfa (andexanet) was specifically developed to reverse factor Xa inhibitors. Its effect on patients who are experiencing major bleeding while being treated with an oral Xa inhibitor or low molecular weight heparin was studied in the ANNEXA 4 ... ...

Title translation	Andexanet alfa: the best antidote for factor Xa inhibitors?
Abstract	Andexanet alfa (andexanet) was specifically developed to reverse factor Xa inhibitors. Its effect on patients who are experiencing major bleeding while being treated with an oral Xa inhibitor or low molecular weight heparin was studied in the ANNEXA 4 study. The main outcome of this study was that anti-factor Xa activity decreased during the 2-hour infusion with andexanet, and that 82% of patients had excellent or good haemostatic efficacy after 12 hours according to pre-specified criteria. Although andexanet is the only specific antidote for factor Xa inhibitors available, an alternative treatment may be high-dose prothrombin concentrate (PCC). With the recent approval by the European Medicines Agency (EMA) but unknown Dutch reimbursement status, the role of andexanet for daily clinical practice in the Netherlands remains to be determined. Notably, and importantly, when treating patients with anticoagulant-associated major bleeding, local haemostatic control and-if relevant-adequate fluid resuscitation are at least as important as choosing the optimal anticoagulation antidote.
MeSH term(s)	Anticoagulants/adverse effects ; Antidotes/therapeutic use ; Blood Coagulation/drug effects ; Factor Xa/therapeutic use ; Factor Xa Inhibitors/adverse effects ; Hemorrhage/chemically induced ; Hemorrhage/drug therapy ; Hemostasis/drug effects ; Heparin, Low-Molecular-Weight/adverse effects ; Humans ; Netherlands ; Recombinant Proteins/therapeutic use
Chemical Substances	Anticoagulants ; Antidotes ; Factor Xa Inhibitors ; Heparin, Low-Molecular-Weight ; PRT064445 ; Recombinant Proteins ; Factor Xa (EC 3.4.21.6)
Language	Dutch
Publishing date	2019-06-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Plant traits and environment: floating leaf blade production and turnover of

Klok, Peter F / van der Velde, Gerard

PeerJ

2022 Volume 10, Page(s) e13976

Abstract: Background: Nymphaeid macrophytes, rooting in the sediment of water bodies and characterized by floating leaves, play an important role in wetland ecosystems. The present research deals with the effects of limited space, limited nutrient availability, ... ...

Abstract	Background: Nymphaeid macrophytes, rooting in the sediment of water bodies and characterized by floating leaves, play an important role in wetland ecosystems. The present research deals with the effects of limited space, limited nutrient availability, water temperature and an unexpected inundation on the production, turnover and plasticity of floating leaves of the globally widespread species Methods: The effects of these environmental conditions were studied in two plots in outdoor concrete tanks (CT1, CT2, mesocosms simulating occurrence in small ponds) and in two plots in the floodplain oxbow lake Bemmelse Strang (BS1, BS2). Plot CT1 was situated in a stand coexisting with helophytes, plot CT2 in a monospecific stand, plot BS1 in the center and plot BS2 at the open water border of a monospecific stand. All floating leaf blades within the plots were marked at appearance at the water surface and subsequently length, width and damage of each leaf and maximum and minimum water temperatures were measured bi-weekly. Area and biomass of leaf blades were calculated based on leaf length and width and were used to calculate turnover rates and production. Results: The growth period started in May and ended mid-October with continuous production of floating leaves during nearly the whole vegetation period. In the tanks the water level was very stable, but the lake underwent an inundation by river water, causing a sudden loss of existing leaves. Considering environmental conditions and based on the assumed ranking from low to high nutrient availability, the ranking of the plots was CT1, CT2, BS1, BS2. This order was found for maximum leaf life span and maximum leaf length, and the reverse order was found for number of leaves, new leaves per day and duration of the vegetation period. Turnover rates appeared to be relatively similar for plots CT1, CT2 and BS1, but for the deeper border plot BS2 lower ratios were found. These results indicate that increased enclosure with expected nutrient limitation causes (1) the production of high numbers of small leaves with larger totals for leaf area and biomass, (2) a shift towards increased sexual reproduction by the production of more flowering stem leaves.
Language	English
Publishing date	2022-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.13976
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Article ; Online: Impact of pulmonary infarction in pulmonary embolism on presentation and outcomes.

Kaptein, F H J / Kroft, L J M / van Dam, L F / Stöger, J L / Ninaber, M K / Huisman, M V / Klok, F A

Thrombosis research

2023 Volume 226, Page(s) 51–55

Abstract: Background: Pulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown.: Aim: To evaluate the predictive value of radiological PI signs at acute ... ...

Abstract	Background: Pulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown. Aim: To evaluate the predictive value of radiological PI signs at acute PE diagnosis on 3-month outcomes. Methods: We studied a convenience cohort with computed tomography pulmonary angiography (CTPA)-confirmed PE for whom extensive 3-month follow-up data were available. The CTPAs were re-evaluated for signs of suspected PI. Associations with presenting symptoms, adverse events (recurrent thrombosis, PE-related readmission and mortality) and self-reported persistent symptoms (dyspnea, pain and post-PE functional impairment) at 3-month follow-up were investigated using univariate Cox regression analysis. Results: At re-evaluation of the CTPAs, 57 of 99 patients (58 %) had suspected PI, comprising a median of 1 % (IQR 1-3) of total lung parenchyma. Patients with suspected PI more often presented with hemoptysis (11 % vs. 0 %) and pleural pain (OR 2.7, 95%CI 1.2-6.2), and with more proximal PE on CTPA (OR 1.6, 95%CI 1.1-2.4) than patients without suspected PI. There was no association with adverse events, persistent dyspnea or pain at 3-month follow-up, but signs of PI predicted more functional impairment (OR 3.03, 95%CI 1.01-9.13). Sensitivity analysis with the largest infarctions (upper tertile of infarction volume) yielded similar results. Conclusions: PE patients radiologically suspected of PI had a different clinical presentation than patients without those signs and reported more functional limitations after 3 months of follow-up, a finding that could guide patient counselling.
MeSH term(s)	Humans ; Pulmonary Infarction/complications ; Computed Tomography Angiography/methods ; Pulmonary Embolism/complications ; Pulmonary Embolism/diagnosis ; Pulmonary Artery ; Dyspnea
Language	English
Publishing date	2023-04-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.04.005
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