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  • 1
    In: Prävention und Gesundheitsförderung, Springer Science and Business Media LLC
    Abstract: As the number of concomitantly used drugs increases, the prevalence of medication risks increases. These include, for example, drug interactions which may reduce or increase the desired and undesired effects of individual drugs. Objectives The POLypharmacy, drug interActions and Risks (POLAR) project aims to contribute to the detection of medication risks in patients with polymedication using methods and processes of the Medical Informatics Initiative (MII) on the basis of “real world data” (inpatient treatment data of university hospitals). In the article, the specific clinical problems are presented and illustrated based on an evaluation example. Materials and methods Specific pharmacological questions are mapped algorithmically and applied in distributed analyses in 13 data integration centers. An essential prerequisite for the application of these algorithms is the core data set structure of the MII, which relies on international information technology, interoperability, and terminology standards. Results In POLAR, it was demonstrated for the first time that inpatient treatment data can be made usable across sites for research questions on drug-related problems based on coordinated, interoperable data exchange formats in a privacy-compliant manner. Conclusions An interim report from the POLAR project shows the first, preliminary result of an analysis. In addition, more general discussions of technical, legal, communicative opportunities and challenges are presented, with a focus on using inpatient treatment data as “real world data” for research purposes.
    Type of Medium: Online Resource
    ISSN: 1861-6755 , 1861-6763
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    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2211781-7
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  • 2
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 89, No. 8 ( 2023-08), p. 2552-2560
    Abstract: Prescribing information should follow a defined structure to help prescribers easily find required information. Often information appears in different sections of Summaries of Product Characteristics (SmPCs) in an inconsistent way. Still unknown is how this inconsistency affects absolute contraindications and how it can be improved. Thisstudy aimed to evaluate the structure of absolute contraindications in SmPCs based on absolute drug–drug contraindications (DDCI) in the section ‘contraindications’ and references to sections ‘special warnings and precautions for use’ (here as ‘warnings’) and ‘interaction with other medicinal products and other forms of interaction’ (here as ‘interactions’). Methods SmPCs of 693 commonly prescribed drugs were analysed regarding absolute DDCI in ‘contraindications’ sections. References to sections on ‘warnings’ and ‘interactions’ were evaluated to characterize information provided about DDCI. Results Of 693 analysed SmPCs, 138 (19.9%) contained ≥1 absolute DDCI. Of 178 SmPCs that referred to sections on ‘warnings’ or ‘interactions’, 131 (73.6%) did not contain further information on absolute DDCI, whereas 47 (26.4%) did. Such additional information was found in sections on ‘interactions’ and ‘warnings’ in 41 (87.2%) and 9 (19.1%) SmPCs, respectively. Conclusions Information regarding absolute DDCI was found not only in sections on ‘contraindications’ but also in sections on ‘warnings’ and ‘interactions’. Information was not given with consistently straightforward phrasing and structure and so can leave uncertainty for prescribers. To improve drug safety, clear definitions and wording for absolute and relative contraindications should be provided, ideally in tables.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 18 ( 2021-06-20), p. 1983-1994
    Abstract: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug–related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS Two hundred two patients were included. Antitumor drug–related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P 〈 .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P 〈 .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P 〈 .001) in favor of the intervention group. CONCLUSION Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Deutscher Arzte-Verlag GmbH ; 2019
    In:  Deutsches Ärzteblatt international ( 2019-11-15)
    In: Deutsches Ärzteblatt international, Deutscher Arzte-Verlag GmbH, ( 2019-11-15)
    Type of Medium: Online Resource
    ISSN: 1866-0452
    Language: German
    Publisher: Deutscher Arzte-Verlag GmbH
    Publication Date: 2019
    detail.hit.zdb_id: 2406159-1
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  • 5
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 88, No. 12 ( 2022-12), p. 5399-5411
    Abstract: Automated checks for medication‐related problems have become a cornerstone of medication safety. In many clinical settings medication checks remain confined to drug–drug interactions because only medication data are available in an adequately coded form, leaving possible contraindicated drug–disease combinations unaccounted for. Therefore, we devised algorithms that identify frequently contraindicated diagnoses based on medication patterns related to these diagnoses. Methods We identified drugs that are associated with diseases constituting common contraindications based on their exclusive use for these conditions (such as allopurinol for gout or salbutamol for bronchial obstruction). Expert‐based and machine learning algorithms were developed to identify diagnoses based on highly specific medication patterns. The applicability, sensitivity and specificity of the approach were assessed by using an anonymized real‐life sample of medication and diagnosis data excerpts from 3506 discharge records of geriatric patients. Results Depending on the algorithm, the desired focus (i.e., sensitivity vs . specificity) and the disease, we were able to identify the diagnoses gout, epilepsy, coronary artery disease, congestive heart failure and bronchial obstruction with a specificity of 44.0–99.8% (95% CI 41.7–100.0%) and a sensitivity of 3.8–83.1% (95% CI 1.0–86.1%). Using only medication data, we were able to identify 123 (51.3%) of 240 contraindications identified by experts with access to medication data and diagnoses. Conclusion This study provides a proof of principle that some key diagnosis‐related contraindications can be identified based on a patient's medication data alone, while others cannot be identified. This approach offers new opportunities to analyse drug–disease contraindications in community pharmacy or clinical routine data.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1498142-7
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  • 6
    In: Healthcare, MDPI AG, Vol. 11, No. 11 ( 2023-06-03), p. 1640-
    Abstract: Generating evidence for the efficacy of an intervention is not sufficient to guarantee its implementation in real-world settings. The randomized AMBORA trial (Medication Safety with Oral Antitumor Therapy) demonstrated that an intensified clinical pharmacological/pharmaceutical care program has substantial benefits for patients, treatment teams, and the healthcare system. Thus, we are now investigating its implementation into routine care within the AMBORA Competence and Consultation Center (AMBORA Center). We perform a multicenter type III hybrid trial following the RE-AIM framework to assess the clinical effectiveness of this care program under real-world conditions, while evaluating the implementation outcomes. Semi-structured stakeholder interviews based on the Consolidated Framework for Implementation Research (CFIR) have been conducted to identify barriers and facilitators. So far, 332 patients treated with oral antitumor drugs have been referred to the AMBORA Center by 66 physicians from 13 independent clinical units. In 20 stakeholder interviews (e.g., with clinic directors), 30% (6/20) of the interviewees anticipated possible barriers which may partly hinder sustainable implementation (e.g., unavailable consultation rooms). Furthermore, important facilitators (e.g., operational processes) were identified. This methodological description adds knowledge on how to structure a hybrid effectiveness–implementation trial and proposes multilevel implementation strategies to improve the medication safety of oral antitumor therapy.
    Type of Medium: Online Resource
    ISSN: 2227-9032
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2721009-1
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  • 7
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 29 ( 2018-07-17)
    Abstract: Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed Anopheles , Aedes , and Culex mosquitoes and Phlebotomus sand flies after feeding on a drug-supplemented blood meal, with IC 50 values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance to common insecticides. Based on allometric scaling of preclinical pharmacokinetics data, we predict that a single human median dose of 260 mg (IQR, 177–407 mg) for afoxolaner, or 410 mg (IQR, 278–648 mg) for fluralaner, could provide an insecticidal effect lasting 50–90 days against mosquitoes and Phlebotomus sand flies. Computational modeling showed that seasonal mass drug administration of such a single dose to a fraction of a regional population would dramatically reduce clinical cases of Zika and malaria in endemic settings. Isoxazolines therefore represent a promising new component of drug-based vector control.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Clinical Pharmacology & Therapeutics Vol. 110, No. 4 ( 2021-10), p. 1075-1086
    In: Clinical Pharmacology & Therapeutics, Wiley, Vol. 110, No. 4 ( 2021-10), p. 1075-1086
    Abstract: Patients treated with oral anticancer agents (e.g., kinase inhibitors) are a high‐risk population for medication errors due to, for example, polymedication, age, and limited adherence. Systematic evaluations regarding frequencies and causes of medication errors and resulting harm are lacking. Our previously published multicenter randomized AMBORA trial revealed that an intensified support by clinical pharmacologists/pharmacists for patients and the treatment team considerably reduced drug‐related problems and improved patient‐reported outcomes. Using this database, we performed a comprehensive, additional analysis focusing on medication errors related to the patients’ complete medication with consideration of the antitumor agents, concomitantly administered drugs, and herb/food intake. Two hundred two patients starting a new oral anticancer drug regardless of the tumor entity were included. Clinical pharmacologists/pharmacists performed advanced medication reviews for 12 weeks. Medication errors were characterized regarding type, cause, patient harm, and the involved medicines. We detected 1.7 medication errors per patient (335/202). Of the medication errors (216/335), 64.5% occurred within the concomitant medication. Patients caused 28.4% of the medication errors. There were 67.8% detected immediately after the start of the new oral regimen, and 14.9% resulted in temporary harm. Drug‐drug or drug‐food interactions accounted for 24.8% of the medication errors. Patients and physicians need to be addressed in strategies for systematic reduction of medication errors during treatment with new oral antitumor drugs. Clinical decision support systems focusing on drug‐drug interactions capture only a minority of the medication errors. Specialists with expertise in clinical pharmacology/pharmacy should support both the treating physicians as well as the patients for improved patient safety.
    Type of Medium: Online Resource
    ISSN: 0009-9236 , 1532-6535
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2040184-X
    SSG: 15,3
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  • 9
    In: Cancers, MDPI AG, Vol. 13, No. 24 ( 2021-12-16), p. 6329-
    Abstract: Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 10
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 378, No. 6615 ( 2022-10-07)
    Abstract: Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century. Expanse of SARS-CoV-2 sequencing capacity in Africa. ( A ) African countries (shaded in gray) and institutions (red circles) with on-site sequencing facilities that are capable of producing SARS-CoV-2 whole genomes locally. ( B ) The number of SARS-CoV-2 genomes produced per country and the proportion of those genomes that were produced locally, regionally within Africa, or abroad. ( C ) Decreased turnaround time of sequencing output in Africa to an almost real-time release of genomic data.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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