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  1. Article ; Online: The Effect of Genotyping on the Number of Pharmacotherapeutic Gene-Drug Interventions in Chronic Kidney Disease Patients.

    Kerskes, Catharina H M / van den Eijnde, Carien J M E / Aarnoudse, Albert-Jan L H J / Grouls, René J E / Deiman, Birgit A L M / Deenen, Maarten J

    Pharmacy (Basel, Switzerland)

    2023  Volume 11, Issue 2

    Abstract: Patients with chronic kidney disease (CKD) stage 3-5 are polypharmacy patients. Many of these drugs are metabolized by cytochrome P450 ( ...

    Abstract Patients with chronic kidney disease (CKD) stage 3-5 are polypharmacy patients. Many of these drugs are metabolized by cytochrome P450 (
    Language English
    Publishing date 2023-04-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737194-3
    ISSN 2226-4787 ; 2226-4787
    ISSN (online) 2226-4787
    ISSN 2226-4787
    DOI 10.3390/pharmacy11020069
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Liquid biopsy-based decision support algorithms for diagnosis and subtyping of lung cancer.

    Visser, Esther / Genet, Sylvia A A M / de Kock, Remco P P A / van den Borne, Ben E E M / Youssef-El Soud, Maggy / Belderbos, Huub N A / Stege, Gerben / de Saegher, Marleen E A / van 't Westeinde, Susan C / Brunsveld, Luc / Broeren, Maarten A C / van de Kerkhof, Daan / Deiman, Birgit A L M / Eduati, Federica / Scharnhorst, Volkher

    Lung cancer (Amsterdam, Netherlands)

    2023  Volume 178, Page(s) 28–36

    Abstract: Objectives: Pathologic subtyping of tissue biopsies is the gold standard for the diagnosis of lung cancer (LC), which could be complicated in cases of e.g. inconclusive tissue biopsies or unreachable tumors. The diagnosis of LC could be supported in a ... ...

    Abstract Objectives: Pathologic subtyping of tissue biopsies is the gold standard for the diagnosis of lung cancer (LC), which could be complicated in cases of e.g. inconclusive tissue biopsies or unreachable tumors. The diagnosis of LC could be supported in a minimally invasive manner using protein tumor markers (TMs) and circulating tumor DNA (ctDNA) measured in liquid biopsies (LBx). This study evaluates the performance of LBx-based decision-support algorithms for the diagnosis of LC and subtyping into small- and non-small-cell lung cancer (SCLC and NSCLC) aiming to directly impact clinical practice.
    Materials and methods: In this multicenter prospective study (NL9146), eight protein TMs (CA125, CA15.3, CEA, CYFRA 21-1, HE4, NSE, proGRP and SCCA) and ctDNA mutations in EGFR, KRAS and BRAF were analyzed in blood of 1096 patients suspected of LC. The performance of individual and combined TMs to identify LC, NSCLC or SCLC was established by evaluating logistic regression models at pre-specified positive predictive values (PPV) of ≥95% or ≥98%. The most informative protein TMs included in the multi-parametric models were selected by recursive feature elimination.
    Results: Single TMs could identify LC, NSCLC and SCLC patients with 46%, 25% and 40% sensitivity, respectively, at pre-specified PPVs. Multi-parametric models combining TMs and ctDNA significantly improved sensitivities to 65%, 67% and 50%, respectively.
    Conclusion: In patients suspected of LC, the LBx-based decision-support algorithms allowed identification of about two-thirds of all LC and NSCLC patients and half of SCLC patients. These models therefore show clinical value and may support LC diagnostics, especially in patients for whom pathologic subtyping is impossible or incomplete.
    MeSH term(s) Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Prospective Studies ; Biomarkers, Tumor ; Phosphopyruvate Hydratase ; Liquid Biopsy
    Chemical Substances antigen CYFRA21.1 ; Biomarkers, Tumor ; Phosphopyruvate Hydratase (EC 4.2.1.11)
    Language English
    Publishing date 2023-02-01
    Publishing country Ireland
    Document type Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2023.01.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2135: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 423: Show issues

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  3. Article ; Online: Toward predicting CYP2D6-mediated variable drug response from

    van der Lee, Maaike / Allard, William G / Vossen, Rolf H A M / Baak-Pablo, Renée F / Menafra, Roberta / Deiman, Birgit A L M / Deenen, Maarten J / Neven, Patrick / Johansson, Inger / Gastaldello, Stefano / Ingelman-Sundberg, Magnus / Guchelaar, Henk-Jan / Swen, Jesse J / Anvar, Seyed Yahya

    Science translational medicine

    2021  Volume 13, Issue 603

    Abstract: Pharmacogenomics is a key component of personalized medicine that promises safer and more effective drug treatment by individualizing drug choice and dose based on genetic profiles. In clinical practice, genetic biomarkers are used to categorize patients ...

    Abstract Pharmacogenomics is a key component of personalized medicine that promises safer and more effective drug treatment by individualizing drug choice and dose based on genetic profiles. In clinical practice, genetic biomarkers are used to categorize patients into *-alleles to predict CYP450 enzyme activity and adjust drug dosages accordingly. However, this approach leaves a large part of variability in drug response unexplained. Here, we present a proof-of-concept approach that uses continuous-scale (instead of categorical) assignments to predict enzyme activity. We used full
    MeSH term(s) Alleles ; Cytochrome P-450 CYP2D6/genetics ; Genotype ; Humans ; Pharmaceutical Preparations ; Prospective Studies ; Tamoxifen
    Chemical Substances Pharmaceutical Preparations ; Tamoxifen (094ZI81Y45) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1)
    Language English
    Publishing date 2021-09-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abf3637
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6941: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients.

    Hulshof, Emma C / de With, Mirjam / de Man, Femke M / Creemers, Geert-Jan / Deiman, Birgit A L M / Swen, Jesse J / Houterman, Saskia / Koolen, Stijn L W / Bins, Sander / Thijs, Anna M J / Laven, Marjan M J / Hövels, Anke M / Luelmo, Saskia A C / Houtsma, Danny / Shulman, Katerina / McLeod, Howard L / van Schaik, Ron H N / Guchelaar, Henk-Jan / Mathijssen, Ron H J /
    Gelderblom, Hans / Deenen, Maarten J

    European journal of cancer (Oxford, England : 1990)

    2022  Volume 162, Page(s) 148–157

    Abstract: Aim: To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan.: Patients and methods: In this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were ... ...

    Abstract Aim: To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan.
    Patients and methods: In this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were pre-therapeutically genotyped for UGT1A1∗28 and UGT1A1∗93. Homozygous variant carriers (UGT1A1 poor metabolisers; PMs) received an initial 30% dose reduction. The primary endpoint was incidence of febrile neutropenia in the first two cycles of treatment. Toxicity in UGT1A1 PMs was compared to a historical cohort of UGT1A1 PMs treated with full dose therapy, and to UGT1A1 non-PMs treated with full dose therapy in the current study. Secondary endpoints were pharmacokinetics, feasibility, and costs.
    Results: Of the 350 evaluable patients, 31 (8.9%) patients were UGT1A1 PM and received a median 30% dose reduction. The incidence of febrile neutropenia in this group was 6.5% compared to 24% in historical UGT1A1 PMs (P = 0.04) and was comparable to the incidence in UGT1A1 non-PMs treated with full dose therapy. Systemic exposure of SN-38 of reduced dosing in UGT1A1 PMs was still slightly higher compared to a standard-dosed irinotecan patient cohort (difference: +32%). Cost analysis showed that genotype-guided dosing was cost-saving with a cost reduction of €183 per patient.
    Conclusion: UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving. Therefore, UGT1A1 genotype-guided dosing of irinotecan should be considered standard of care in order to improve individual patient safety.
    MeSH term(s) Camptothecin/adverse effects ; Costs and Cost Analysis ; Febrile Neutropenia ; Genotype ; Glucuronosyltransferase/genetics ; Humans ; Irinotecan/adverse effects ; Prospective Studies
    Chemical Substances Irinotecan (7673326042) ; Glucuronosyltransferase (EC 2.4.1.17) ; Camptothecin (XT3Z54Z28A)
    Language English
    Publishing date 2022-01-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 82061-1
    ISSN 1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
    ISSN (online) 1879-0852
    ISSN 0277-5379 ; 0959-8049 ; 0964-1947
    DOI 10.1016/j.ejca.2021.12.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 456: Show issues Location:
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    Zs.MO 583: Show issues

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  5. Article ; Online: High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment

    Sluimer, John / van den Akker, Willem M.R. / Goderski, Gabriel / Swart, Arno / van der Veer, Bas / Cremer, Jeroen / Chung, Ngoc Hoa / Molenkamp, Richard / Voermans, Jolanda / Guldemeester, Judith / van der Eijk, Annemiek / de Jong, Menno D. / Mithoe, Glen / Hermans, Mirjam H.A. / de Beer, Jessica L. / Wessels, Els / von Wintersdorff, Christian / Pas, Suzan / Verweij, Jaco J. /
    Melchers, Willem J.G. / van de Bovenkamp, Jeroen H.B. / Vahidnia, Ali / Gard, Lilli / Schuurman, Rob / Wintermans, Bas / Leversteijn-van Hall, Maurine / Smits, Paul / de Groot, Theun / Deiman, Birgit A.L.M. / Bart, Aldert / van der Reijden, Wil / Svraka-Latifovic, Sanela / van der Zanden, Adri G.M. / Thijsen, Steven / Schubbert, Rainer / Dreesens, Lisa L. / van Duijn, Gert / Ong, David S.Y. / Oostra, Monique / Bruisten, Sylvia / van Trijp, Marijke / Pettersson, Annika / van Burgel, Nathalie D. / Oudbier, Joke / van der Linden, Michael / van Rijn, Michiel / Bos, Martine P. / Rossen, John / Schuurs, Theo A. / Tacken, Mirriam G.J. / Presser, Lance D. / Meijer, Adam

    Scientific Reports

    2024  Volume 14, Issue 1

    Abstract: A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This ... ...

    Abstract A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.
    Keywords Life Science
    Subject code 670
    Language English
    Publishing country nl
    Document type Article ; Online
    ZDB-ID 2615211-3
    ISSN 2045-2322
    ISSN 2045-2322
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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