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Article ; Online: Simulation modeling for stratified breast cancer screening – a systematic review of cost and quality of life assumptions

Matthias Arnold

BMC Health Services Research, Vol 17, Iss 1, Pp 1-

2017 Volume 19

Abstract: Abstract Background The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility ... ...

Abstract	Abstract Background The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility parameters received only little attention. This systematic review assesses simulation models for stratified breast cancer screening based on their cost and utility parameters in each phase of breast cancer screening and care. Methods A literature review was conducted to compare economic evaluations with simulation models of personalized breast cancer screening. Study quality was assessed using reporting guidelines. Cost and utility inputs were extracted, standardized and structured using a care delivery framework. Studies were then clustered according to their study aim and parameters were compared within the clusters. Results Eighteen studies were identified within three study clusters. Reporting quality was very diverse in all three clusters. Only two studies in cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in the quality appraisal. In addition to the quality appraisal, this review assessed if the simulation models were consistent in integrating all relevant phases of care, if utility parameters were consistent and methodological sound and if cost were compatible and consistent in the actual parameters used for screening, diagnostic work up and treatment. Of 18 studies, only three studies did not show signs of potential bias. Conclusion This systematic review shows that a closer look into the cost and utility parameter can help to identify potential bias. Future simulation models should focus on integrating all relevant phases of care, using methodologically sound utility parameters and avoiding inconsistent cost parameters.
Keywords	Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2017-12-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is risk-stratified breast cancer screening economically efficient in Germany?

Matthias Arnold / Katharina Pfeifer / Anne S Quante

PLoS ONE, Vol 14, Iss 5, p e

2019 Volume 0217213

Abstract: OBJECTIVES:Risk stratification has so far been evaluated under the assumption that women fully adhere to screening recommendations. However, the participation in German cancer screening programs remains low at 54%. The question arises whether risk- ... ...

Abstract	OBJECTIVES:Risk stratification has so far been evaluated under the assumption that women fully adhere to screening recommendations. However, the participation in German cancer screening programs remains low at 54%. The question arises whether risk-stratified screening is economically efficient under the assumption that adherence is not perfect. METHOD:We have adapted a micro-simulation Markov model to the German context. Annual, biennial, and triennial routine screening are compared with five risk-adapted strategies using thresholds of relative risk to stratify screening frequencies. We used three outcome variables (mortality reduction, quality-adjusted life years, and false-positive results) under the assumption of full adherence vs. an adherence rate of 54%. Strategies are evaluated using efficiency frontiers and probabilistic sensitivity analysis (PSA). RESULTS:The reduced adherence rate affects both performance and cost; incremental cost-effectiveness ratios remain constant. The results of PSA show that risk-stratified screening strategies are more efficient than biennial routine screening under certain conditions. At any willingness-to-pay (WTP), there is a risk-stratified alternative with a higher likelihood of being the best choice. However, without explicit decision criteria and WTP, risk-stratified screening is not more efficient than biennial routine screening. Potential improvements in the adherence rates have significant health gains and budgetary implications. CONCLUSION:If the participation rate for mammographic screening is as low as in Germany, stratified screening is not clearly more efficient than routine screening but dependent on the WTP. A more promising design for future stratified strategies is the combination of risk stratification mechanisms with interventions to improve the low adherence in selected high-risk groups.
Keywords	Medicine ; R ; Science ; Q
Subject code	332
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A one stop shop for cost-effectiveness evidence? Recommendations for improving Disease Control Priorities

Matthias Arnold / Susan Griffin / Jessica Ochalek / Paul Revill / Simon Walker

Cost Effectiveness and Resource Allocation, Vol 17, Iss 1, Pp 1-

2019 Volume 4

Abstract: Abstract Setting out a health benefits package (HBP) of interventions to be prioritised for funding is an important step towards achieving universal health coverage in low and middle income countries. The 3rd version of the Disease Control Priorities ( ... ...

Abstract	Abstract Setting out a health benefits package (HBP) of interventions to be prioritised for funding is an important step towards achieving universal health coverage in low and middle income countries. The 3rd version of the Disease Control Priorities (DCP3) database, and other similar databases, aim to establishing a single point of reference (“one stop shop”) for cost effectiveness evidence to inform HBP design and other policy making. We reflect upon our experiences in using DCP3 for HBP design and offer suggestions for improving the future reporting of cost-effectiveness evidence. We appraise DCP3 based on generalisability, level of detail, and accessibility. We find that DCP and similar initiatives should be commended for the systematic assessment of a vast array of cost-effectiveness studies—the magnitude of such an endeavour is impressive in its own right. However, there are flaws. In future, providing disaggregated estimates of costs and effects, quantifying uncertainty, and systematically assessing the context in which estimates apply would make this evidence more useful for decision makers.
Keywords	Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

Kamil Borkowski / Ameer Y. Taha / Theresa L. Pedersen / Philip L. De Jager / David A. Bennett / Matthias Arnold / Rima Kaddurah-Daouk / John W. Newman

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy ... ...

Abstract	Abstract Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy metabolism, including oxylipins, endocannabinoids, bile acids, and steroid hormones to identify metabolic biomarkers of mild cognitive impairment (MCI). Serum samples (n = 212) were obtained from subjects with or without MCI opportunistically collected with incomplete fasting state information. To maximize power and stratify the analysis of metabolite associations with MCI by the fasting state, we developed an algorithm to predict subject fasting state when unknown (n = 73). In non-fasted subjects, linoleic acid and palmitoleoyl ethanolamide levels were positively associated with perceptual speed. In fasted subjects, soluble epoxide hydrolase activity and tauro-alpha-muricholic acid levels were negatively associated with perceptual speed. Other cognitive domains showed associations with bile acid metabolism, but only in the non-fasted state. Importantly, this study shows unique associations between serum metabolites and cognitive function in the fasted and non-fasted states and provides a fasting state prediction algorithm based on measurable metabolites.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PhenoDis

Angela Adler / Pia Kirchmeier / Julian Reinhard / Barbara Brauner / Irmtraud Dunger / Gisela Fobo / Goar Frishman / Corinna Montrone / H.-Werner Mewes / Matthias Arnold / Andreas Ruepp

Orphanet Journal of Rare Diseases, Vol 13, Iss 1, Pp 1-

a comprehensive database for phenotypic characterization of rare cardiac diseases

2018 Volume 8

Abstract: Abstract Background Thoroughly annotated data resources are a key requirement in phenotype dependent analysis and diagnosis of diseases in the area of precision medicine. Recent work has shown that curation and systematic annotation of human phenome data ...

Abstract	Abstract Background Thoroughly annotated data resources are a key requirement in phenotype dependent analysis and diagnosis of diseases in the area of precision medicine. Recent work has shown that curation and systematic annotation of human phenome data can significantly improve the quality and selectivity for the interpretation of inherited diseases. We have therefore developed PhenoDis, a comprehensive, manually annotated database providing symptomatic, genetic and imprinting information about rare cardiac diseases. Results PhenoDis includes 214 rare cardiac diseases from Orphanet and 94 more from OMIM. For phenotypic characterization of the diseases, we performed manual annotation of diseases with articles from the biomedical literature. Detailed description of disease symptoms required the use of 2247 different terms from the Human Phenotype Ontology (HPO). Diseases listed in PhenoDis frequently cover a broad spectrum of symptoms with 28% from the branch of ‘cardiovascular abnormality’ and others from areas such as neurological (11.5%) and metabolism (6%). We collected extensive information on the frequency of symptoms in respective diseases as well as on disease-associated genes and imprinting data. The analysis of the abundance of symptoms in patient studies revealed that most of the annotated symptoms (71%) are found in less than half of the patients of a particular disease. Comprehensive and systematic characterization of symptoms including their frequency is a pivotal prerequisite for computer based prediction of diseases and disease causing genetic variants. To this end, PhenoDis provides in-depth annotation for a complete group of rare diseases, including information on pathogenic and likely pathogenic genetic variants for 206 diseases as listed in ClinVar. We integrated all results in an online database ( http://mips.helmholtz-muenchen.de/phenodis/ ) with multiple search options and provide the complete dataset for download. Conclusion PhenoDis provides a comprehensive set of manually annotated rare ...
Keywords	Rare cardiac diseases ; Heart ; Phenotype ; Genotype ; Precision medicine ; Genetic disorders ; Medicine ; R
Subject code	610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cis-acting polymorphisms affect complex traits through modifications of microRNA regulation pathways.

Matthias Arnold / Daniel C Ellwanger / Mara L Hartsperger / Arne Pfeufer / Volker Stümpflen

PLoS ONE, Vol 7, Iss 5, p e

2012 Volume 36694

Abstract: Genome-wide association studies (GWAS) have become an effective tool to map genes and regions contributing to multifactorial human diseases and traits. A comparably small number of variants identified by GWAS are known to have a direct effect on protein ... ...

Abstract	Genome-wide association studies (GWAS) have become an effective tool to map genes and regions contributing to multifactorial human diseases and traits. A comparably small number of variants identified by GWAS are known to have a direct effect on protein structure whereas the majority of variants is thought to exert their moderate influences on the phenotype through regulatory changes in mRNA expression. MicroRNAs (miRNAs) have been identified as powerful posttranscriptional regulators of mRNAs. Binding to their target sites, which are mostly located within the 3'-untranslated region (3'-UTR) of mRNA transcripts, they modulate mRNA expression and stability. Until today almost all human mRNA transcripts are known to harbor at least one miRNA target site with an average of over 20 miRNA target sites per transcript. Among 5,101 GWAS-identified sentinel single nucleotide polymorphisms (SNPs) that correspond to 18,884 SNPs in linkage disequilibrium (LD) with the sentinels (r2 ≥ 0.8) we identified a significant overrepresentation of SNPs that affect the 3'-UTR of genes (OR = 2.33, 95% CI = 2.12-2.57, P < 10(-52)). This effect was even stronger considering all SNPs in one LD bin a single signal (OR = 4.27, 95% CI = 3.84-4.74, P < 10(-114)). Based on crosslinking immunoprecipitation data we identified four mechanisms affecting miRNA regulation by 3'-UTR mutations: (i) deletion or (ii) creation of miRNA recognition elements within validated RNA-induced silencing complex binding sites, (iii) alteration of 3'-UTR splicing leading to a loss of binding sites, and (iv) change of binding affinity due to modifications of 3'-UTR folding. We annotated 53 SNPs of a total of 288 trait-associated 3'-UTR SNPs as mediating at least one of these mechanisms. Using a qualitative systems biology approach, we demonstrate how our findings can be used to support biological interpretation of GWAS results as well as to provide new experimentally testable hypotheses.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 570
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

Gemma Cadby / Corey Giles / Phillip E. Melton / Kevin Huynh / Natalie A. Mellett / Thy Duong / Anh Nguyen / Michelle Cinel / Alex Smith / Gavriel Olshansky / Tingting Wang / Marta Brozynska / Mike Inouye / Nina S. McCarthy / Amir Ariff / Joseph Hung / Jennie Hui / John Beilby / Marie-Pierre Dubé /

Gerald F. Watts / Sonia Shah / Naomi R. Wray / Wei Ling Florence Lim / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Tenielle Porter / Michael Vacher / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Kevin Taddei / Matthias Arnold / Gabi Kastenmüller / Kwangsik Nho / Andrew J. Saykin / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / John Blangero / Peter J. Meikle / Eric K. Moses

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 17

Abstract: Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD. ...

Abstract	Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.
Keywords	Science ; Q
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

Kevin Huynh / Wei Ling Florence Lim / Corey Giles / Kaushala S. Jayawardana / Agus Salim / Natalie A. Mellett / Adam Alexander T. Smith / Gavriel Olshansky / Brian G. Drew / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Matthias Arnold / Kwangsik Nho /

Andrew J. Saykin / Rebecca Baillie / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / Peter J. Meikle

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 11

Abstract: The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma ... ...

Abstract	The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
Keywords	Science ; Q
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

Andrew J. Saykin / Rebecca Baillie / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / Peter J. Meikle

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 11

Abstract	The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
Keywords	Science ; Q
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome

Matthias Arnold / Kwangsik Nho / Alexandra Kueider-Paisley / Tyler Massaro / Kevin Huynh / Barbara Brauner / Siamak MahmoudianDehkordi / Gregory Louie / M. Arthur Moseley / J. Will Thompson / Lisa St John-Williams / Jessica D. Tenenbaum / Colette Blach / Rui Chang / Roberta D. Brinton / Rebecca Baillie / Xianlin Han / John Q. Trojanowski / Leslie M. Shaw /

Ralph Martins / Michael W. Weiner / Eugenia Trushina / Jon B. Toledo / Peter J. Meikle / David A. Bennett / Jan Krumsiek / P. Murali Doraiswamy / Andrew J. Saykin / Rima Kaddurah-Daouk / Gabi Kastenmüller

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 12

Abstract: Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum. ...

Abstract	Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.
Keywords	Science ; Q
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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