Mouse Population-Based Toxicology for Personalized Medicine and Improved Safety Prediction

2016 ◽  
pp. 314-329 ◽  
Author(s):  
Alison H. Harrill
Keyword(s):  
Personalized Medicine ◽  
Population Based ◽  
Mouse Population

HEALTH TECHNOLOGY ASSESSMENT AND PERSONALIZED MEDICINE: ARE ECONOMIC EVALUATION GUIDELINES SUFFICIENT TO SUPPORT DECISION MAKING?

2014 ◽  
Vol 30 (2) ◽  
pp. 179-187 ◽  
Author(s):  
Don Husereau ◽  
Deborah A. Marshall ◽  
Adrian R. Levy ◽  
Stuart Peacock ◽  
Jeffrey S. Hoch
Keyword(s):  
Decision Making ◽  
Economic Evaluation ◽  
Personalized Medicine ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Population Based ◽  
New Paradigm ◽  
Current Guidance ◽  
Support Decision Making

Background: Many jurisdictions delivering health care, including Canada, have developed guidance for conducting economic evaluation, often in the service of larger health technology assessment (HTA) and reimbursement processes. Like any health intervention, personalized medical (PM) interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. However, current approaches to economic evaluation to support decision making have been largely developed from population-based approaches to therapy—that is, evaluating the costs and consequences of single interventions across single populations. This raises the issue as to whether these methods, as they are or more refined, are adequate to address more targeted approaches to therapy, or whether a new paradigm for assessing value in PM is required.Objectives: We describe specific issues relevant to the economic evaluation of diagnostics-based PM and assess whether current guidance for economic evaluation is sufficient to support decision making for PM interventions.Methods: Issues were identified through literature review and informal interviews with national and international experts (n = 10) in these analyses. This article elaborates on findings and discussion at a workshop held in Ottawa, Canada, in January 2012.Results: Specific issues related to better guiding economic evaluation of personalized medicine interventions include: how study questions are developed, populations are characterized, comparators are defined, effectiveness is evaluated, outcomes are valued and how resources are measured. Diagnostics-based PM also highlights the need for analyses outside of economic evaluation to support decision making.Conclusions: The consensus of this group of experts is that the economic evaluation of diagnostics-based PM may not require a new paradigm. However, greater complexity means that existing approaches and tools may require improvement to undertake these more analyses.

scholarly journals Genetic Background Shapes Phenotypic Response to Diet for Adiposity in the Collaborative Cross

2021 ◽  
Vol 11 ◽  
Author(s):  
Phoebe Yam ◽  
Jody Albright ◽  
Melissa VerHague ◽  
Erik R. Gertz ◽  
Fernando Pardo-Manuel de Villena ◽  
...  
Keyword(s):  
Complex Traits ◽  
Phenotypic Diversity ◽  
Inbred Mouse ◽  
Population Based ◽  
Collaborative Cross ◽  
Dietary Recommendations ◽  
Mouse Population ◽  
Before And After ◽  
Induced Changes

Defined as chronic excessive accumulation of adiposity, obesity results from long-term imbalance between energy intake and expenditure. The mechanisms behind how caloric imbalance occurs are complex and influenced by numerous biological and environmental factors, especially genetics, and diet. Population-based diet recommendations have had limited success partly due to the wide variation in physiological responses across individuals when they consume the same diet. Thus, it is necessary to broaden our understanding of how individual genetics and diet interact relative to the development of obesity for improving weight loss treatment. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, we analyzed body composition, metabolic rate, clinical blood chemistries, and circulating metabolites in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after 8 weeks of feeding either a high protein or high fat high sucrose diet. At both baseline and post-diet, adiposity and other obesity-related traits exhibited a broad range of phenotypic variation based on CC strain; diet-induced changes in adiposity and other traits also depended largely on CC strain. In addition to estimating heritability at baseline, we also quantified the effect size of diet for each trait, which varied by trait and experimental diet. Our findings identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits, and highlight the importance of accounting for genetic differences when making dietary recommendations.

scholarly journals Community consultation and communication for a population-based DNA biobank: The Marshfield clinic personalized medicine research project

2008 ◽  
Vol 146A (23) ◽  
pp. 3026-3033 ◽  
Author(s):  
Catherine A. McCarty ◽  
Donna Chapman-Stone ◽  
Teresa Derfus ◽  
Philip F. Giampietro ◽  
Norman Fost ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Population Based ◽  
Community Consultation ◽  
Research Project ◽  
Medicine Research ◽  
Marshfield Clinic

scholarly journals Personalized laboratory medicine: a patient-centered future approach

2018 ◽  
Vol 56 (12) ◽  
pp. 1981-1991 ◽  
Author(s):  
Irena Prodan Žitnik ◽  
Darko Černe ◽  
Irene Mancini ◽  
Lisa Simi ◽  
Mario Pazzagli ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Treatment Strategies ◽  
Population Based ◽  
Laboratory Medicine ◽  
Response To Treatment ◽  
Medical Decision ◽  
Patient Centered ◽  
Evidence Based Treatment ◽  
Palliative Patient ◽  
The Individual

Abstract In contrast to population-based medical decision making, which emphasizes the use of evidence-based treatment strategies for groups of patients, personalized medicine is based on optimizing treatment at the level of the individual patient. The creation of molecular profiles of individual patients was made possible by the advent of “omics” technologies, based on high throughput instrumental techniques in combination with biostatistics tools and artificial intelligence. The goal of personalized laboratory medicine is to use advanced technologies in the process of preventive, curative or palliative patient management. Personalized medicine does not rely on changes in concentration of a single molecular marker to make a therapeutic decision, but rather on changes of a profile of markers characterizing an individual patient’s status, taking into account not only the expected response to treatment of the disease but also the expected response of the patient. Such medical approach promises a more effective diagnostics with more effective and safer treatment, as well as faster recovery and restoration of health and improved cost effectiveness. The laboratory medicine profession is aware of its key role in personalized medicine, but to empower the laboratories, at least an enhancement in cooperation between disciplines within laboratory medicine will be necessary.

scholarly journals Genetic background influences the effect of thirdhand smoke exposure on anxiety and memory in Collaborative Cross mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li He ◽  
Pin Wang ◽  
Suzyann F. Schick ◽  
Abel Huang ◽  
Peyton Jacob ◽  
...  
Keyword(s):  
Genetic Background ◽  
Tracking System ◽  
Critical Role ◽  
Memory Loss ◽  
Population Based ◽  
Collaborative Cross ◽  
The Other ◽  
Mouse Population ◽  
Thirdhand Smoke ◽  
Host Genetic

AbstractGrowing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects. However, it is unclear how THS exposure affects behavior and how host genetic background modulates phenotypic changes. Here we used the Collaborative Cross (CC) mouse population-based model to assess behavioral alterations immediately after THS exposure from 4 to 9 weeks of age. We first measured anxiety-like behavior in six strains using light/dark box combined with a custom multivariate mouse tracking system. We developed an anxiety risk scoring system based on anxiety-related traits and then evaluated the THS impact on them. THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009), but increased anxiety risk in CC036 (P < 0.001), while the other three strains did not show significant changes in anxiety-related traits. Such differences were driven by female mice for the six measures of anxiety-like behavior. Memory potential was measured in the same cohort of mice using the passive avoidance assay. Both THS-exposed male and female CC019 mice displayed significant memory loss compared to controls while no significant changes were found in the other five strains. This study provides strong evidence that THS exposure leads to strain-dependent changes in anxiety-like behavior and memory, suggesting that host genetic variations play a critical role in individual susceptibility to THS-induced effects.

scholarly journals Laboratory-Based Resources for COVID-19 Diagnostics: Traditional Tools and Novel Technologies. A Perspective of Personalized Medicine

2021 ◽  
Vol 11 (1) ◽  
pp. 42
Author(s):  
Boris G. Andryukov ◽  
Natalya N. Besednova ◽  
Tatyana A. Kuznetsova ◽  
Ludmila N. Fedyanina
Keyword(s):  
Personalized Medicine ◽  
Large Scale ◽  
Diagnostic Testing ◽  
Population Based ◽  
Diagnostic Tools ◽  
Rapid Diagnostics ◽  
Retrospective Diagnosis ◽  
Novel Technologies ◽  
Population Immunity ◽  
Number Of Patients

The coronavirus infection 2019 (COVID-19) pandemic, caused by the highly contagious SARS-CoV-2 virus, has provoked a global healthcare and economic crisis. The control over the spread of the disease requires an efficient and scalable laboratory-based strategy for testing the population based on multiple platforms to provide rapid and accurate diagnosis. With the onset of the pandemic, the reverse transcription polymerase chain reaction (RT-PCR) method has become a standard diagnostic tool, which has received wide clinical use. In large-scale and repeated examinations, these tests can identify infected patients with COVID-19, with their accuracy, however, dependent on many factors, while the entire process takes up to 6–8 h. Here we also describe a number of serological systems for detecting antibodies against SARS-CoV-2. These are used to assess the level of population immunity in various categories of people, as well as for retrospective diagnosis of asymptomatic and mild COVID-19 in patients. However, the widespread use of traditional diagnostic tools in the context of the rapid spread of COVID-19 is hampered by a number of limitations. Therefore, the sharp increase in the number of patients with COVID-19 necessitates creation of new rapid, inexpensive, sensitive, and specific tests. In this regard, we focus on new laboratory technologies such as loop mediated isothermal amplification (LAMP) and lateral flow immunoassay (LFIA), which have proven to work well in the COVID-19 diagnostics and can become a worthy alternative to traditional laboratory-based diagnostics resources. To cope with the COVID-19 pandemic, the healthcare system requires a combination of various types of laboratory diagnostic testing techniques, whodse sensitivity and specificity increases with the progress in the SARS-CoV-2 research. The testing strategy should be designed in such a way to provide, depending on the timing of examination and the severity of the infection in patients, large-scale and repeated examinations based on the principle: screening–monitoring–control. The search and development of new methods for rapid diagnostics of COVID-19 in laboratory, based on new analytical platforms, is still a highly important and urgent healthcare issue. In the final part of the review, special emphasis is made on the relevance of the concept of personalized medicine to combat the COVID-19 pandemic in the light of the recent studies carried out to identify the causes of variation in individual susceptibility to SARS-CoV-2 and increase the efficiency and cost-effectiveness of treatment.

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