Precision Medicine in Clinical Practice

Acknowledgments
Contents
1: Principles of Precision Medicine
1.1 An Introduction to Precision Medicine in Clinical Practice
1.2 Definition of Precision Medicine
1.3 Pharmacogenomics
1.4 Precision Medicine in Clinical Practice
1.4.1 The Effectiveness of Care
1.4.2 Preventive Medicine
1.4.3 Cost-Effectiveness
1.4.4 New Taxonomy
1.4.5 Population Healthcare
1.5 Precision Medicine and Evidence-Based Medicine
1.6 Genomics Precision Medicine
1.7 “Omics” and Precision Medicine
1.8 Personalized Medicine, Artificial Intelligence, and Digital Twin
References
2: Principles of Pharmacogenomics and Pharmacogenetics
2.1 Introduction to Pharmacogenomics and Pharmacogenetics
2.2 Pharmacodynamics and Pharmacokinetics
2.3 Phenoconversion
2.4 Pharmacogenomics Nomenclature
2.5 Genetic Variations
2.6 Pharmacogenomics in Clinical Practice
2.7 Pharmacogenomics in Drug Development
2.8 Pharmacogenomics in Oncology
2.9 Germline Pharmacogenomics Association with Treatment Efficacy and Toxicity
2.9.1 CYP2D6 and Tamoxifen
2.9.2 Fluoropyrimidines and DPYD
2.10 Implementation of Pharmacogenomics in Oncology
2.11 Pharmacogenomics in Psychiatry
2.12 Implementation of Psychopharmacogenomics in Psychiatry
2.13 Pharmacogenomics in Pain Management
2.13.1 CYP2D6
2.13.2 OPRM1
2.14 Pharmacogenomics in Diabetes
2.15 Future Perspective of Pharmacogenetics in Diabetes
2.16 Pharmacogenomics Resources
2.17 Pharmacogenomics Cases in Practice
2.17.1 Case Study 1: Cardiology
2.17.2 Case Study 2: Depression
2.17.3 Case Study 3: Pain and Phenoconversion
2.17.4 Case Study 4: Schizophrenia and Phenoconversion
2.17.5 Case Study 4: Comprehensive Case Study
References
3: Precision Medicine in Oncology and Cancer Therapeutics
3.1 Introduction
3.2 Precision Oncology 1.0: New Lenses for an Old Quest
3.3 Precision Oncology 2.0: The Double Helix and the Rise of Biotechnology
3.4 Precision Oncology 3.0: Cancer, a Diseases of the Genome
3.4.1 Next-Generation Biopharmaceutical Products
3.4.2 Multi-targeted Therapy
3.4.3 New Ways of Reprogramming the Immune System
3.4.4 Advances in Adoptive Cell Therapies
3.4.5 Therapeutic Vaccines
3.5 Oncology 4.0: Fighting Cancer from Multiple Fronts in the Fourth Industrial Revolution
3.5.1 Single-Cell Multiomics for Precision Medicine
3.5.2 Network Medicine and AI
3.5.3 Functional Tests and Organoid-Driven Precision Medicine
3.5.4 A New Era of Biomarkers: Genomic Signatures, Composite Biomarkers, Driver-Pathway Biomarkers, Synthetic Biomarkers
3.5.5 Driver Networks as Biomarkers
3.5.6 The Future of Precision Oncology: The Rise of Digital Twins
3.6 Implementing Precision Oncology in Europe
3.6.1 How Do We Make P4 Medicine a Reality in Medical Practice by Involving Patients, Doctors, Members of the Medical Community, and Citizens?
References
4: Precision Medicine in Cardiovascular Disease Practice
4.1 Introduction
4.2 Drugs
4.2.1 Warfarin
4.2.2 VKORC1
4.2.3 CYP2C9
4.2.4 CYP4F2
4.2.5 P2Y12 Inhibitors
4.2.6 Statin
4.3 Cardiomyopathies
4.3.1 Hypertrophic Cardiomyopathy (HCM)
4.3.2 Dilated Cardiomyopathy (DCM)
4.3.3 Restrictive Cardiomyopathy (RCM)
4.4 Thoracic Aortic Aneurysm/Aortic Dissection (TAAD)
4.5 Valvopathies
4.5.1 Mitral Valve Replacement
4.6 Arrhythmia
4.6.1 Long QT Syndrome (LQTS)
4.6.2 Brugada Syndrome (BrS)
4.6.3 Short QT Syndrome (SQTS)
4.6.4 Idiopathic Ventricular Fibrillation (IVF)
4.6.5 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
4.6.6 Progressive Cardiac Conduction System Disease (PCCD)
4.7 Coronary Artery Disease (CAD)
4.7.1 Genes and Mechanism
4.7.2 Premature CAD
4.7.3 Vascular Inflammation and Remodeling
4.8 Hypertension
4.9 Recognizing Ethical Issues and How to Deal with Them
4.10 Digital Twin “Prospective of Precision Medicine in Cardiology”
References
5: Precision Medicine in Endocrinology Practice
5.1 Precision Diabetes Medicine
5.2 Some Lessons from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Consensus Report for Precision Medicine in Diabetes
5.3 Precision Diagnostics in Diabetes
5.4 Precision Diagnostics in T1D and T2DM
5.5 Precision Therapeutics of Diabetes
5.6 Precision Prevention
5.7 Precision Treatment/Pharmacogenomics
5.8 Precision Medicine in Osteoporosis
5.9 Precision Medicine in Polycystic Ovary Syndrome
5.10 Thyroid Cancer
5.11 Molecular Genetics of Thyroid Cancer
5.12 Precision Medicine for Thyroid Cancer
5.13 Precision Medicine for Obesity
5.14 Obesity Classification
5.15 Omics and Obesity
5.15.1 Genomics
5.15.2 Transcriptomics
5.15.3 Metabolomics
5.15.4 Microbiome
5.15.5 Pharmacogenomics
5.15.6 Nutrigenetics and Nutrigenomics
5.16 Challenges
5.17 Future Perspective of Precision Medicine in Endocrinology
References
6: Precision Medicine in Psychiatric Disorders
6.1 Introduction
6.2 A Special Case for Psychiatry
6.2.1 Psychiatric Disorders Are Multigenic, Multifactorial, and Highly Heterogeneous
6.2.2 From Evidence-Based Through Personalized Toward Precision Psychiatry
6.2.3 The Issue of Psychiatric Measurement and Phenotyping: Objective Markers for Subjective Suffering
6.3 Making Sense of the Information in Precision Psychiatry
6.3.1 Big Data Analytics and Machine Learning Toward a Systems Biological Approach in Understanding and Treating Neuropsychiatric Disorders
6.3.2 Modelling and Predicting Disease and Treatment Characteristics in Precision Psychiatry
6.4 Special Aspects in Precision Psychiatry
6.4.1 The Role of the Blood-Brain-Barrier
6.4.2 Longitudinal Perspective and Staging Model of Neuropsychiatric Disorders
6.4.3 Precision Psychotherapy: Predicting the Efficacy of Psychological Treatment and Identifying Patients Who Would Benefit
6.4.4 Focusing on Comorbidities and Environmental Effects in Precision Psychiatry: The Diseasome Approach
6.5 Clinical Application of Precision Psychiatry
6.5.1 The Current State of Precision Psychiatry in Mood Disorders
6.5.2 The Current State of Precision Psychiatry in Schizophrenia
6.6 Challenges, Obstacles, and Limitations in Precision Psychiatry
6.7 Conclusion
References
7: Precision Public Health Perspectives
7.1 Population Health Versus Public Health
7.2 Introduction to Public Health (PH) and Personalized Medicine (PM)
7.3 Impact of Personalized Medicine in Public Health
7.4 Direct Impact
7.5 Indirect Impact: Genetic Information on Preventive Applications, Diagnostic Disease, and Targeted Therapies
7.6 Public Involvement in PM
7.7 Personalized Public Health and Equity
References
8: DNA Technologies in Precision Medicine and Pharmacogenetics
8.1 Introduction
8.2 NGS Technology Procedures: Its Important Applications and Related Different Databases
8.3 Whole-Genome Sequencing
8.4 Whole-Exome Sequencing
8.5 Clinical Exome Sequencing
8.6 Whole Transcriptome Sequencing
8.7 Targeted Sequencing
8.8 Single-Cell Sequencing
8.9 DNA Microarray
8.10 Conclusion
References
9: Precision Medicine Initiatives
9.1 Introduction
9.2 Precision Medicine Initiatives
9.2.1 The Precision Medicine Initiative (PMI) (United States)
9.2.2 Electronic Medical Records and Genomics (eMERGE)
9.2.3 The Clinical Sequencing Evidence-Generating Research (CSER)
9.2.4 Implementing GeNomics in PracTicE (IGNITE)
9.2.5 ALL of Us
9.2.6 100,000 Genomes
9.2.7 France: The Plan for Genomic Medicine (PFMG) and Health Data Hub
9.2.8 Japan: Initiative on Rare and Undiagnosed Diseases
9.2.9 GenomeCanada
9.2.10 World Economic Forum (WEF): Center for the Fourth Industrial Revolution
9.2.11 European Initiatives Dedicated to Personalized Medicine
9.3 Initiatives Related to Pancreatic Pathology
9.3.1 PanCAN (United States)
9.3.2 Enhanced Pancreatic-Cancer Profiling for Individualized Care (EPPIC) (Canada)
9.3.3 The PancREatic Cancer OrganoiDs rEsearch (PRECODE) (Germany)
9.3.4 The Australian Pancreatic Cancer Genome Initiative (APGI) (Australia)
9.4 Initiatives with the Most Focus on Diabetes
9.4.1 Nordic Precision Medicine Initiative (NPMI) (North Europe)
9.4.2 EPMPP, FinnGen, GAPS, deCODE
9.4.3 Saudi Human Genome Project (SHGP)
9.5 Initiatives Related to Alzheimer’s Disease (AD)
9.5.1 The Genetic Frontotemporal dementia Initiative (GENFI)
9.5.2 The Dominantly Inherited Alzheimer Network (DIAN)
9.5.3 Alzheimer Precision Medicine Initiative (APMI)
9.5.4 Dementias Platform United Kingdom (DPUK)
9.5.5 EU Joint Program on Neurodegenerative Disease Research (EU JPND)
9.5.6 European Prevention of Alzheimer’s Dementia (EPAD)
9.5.7 The AETIONOMY Project
9.5.8 The Women’s Brain Project (WBP)
References
10: Economic Aspects in Precision Medicine and Pharmacogenomics
10.1 The Importance of Economic Evaluation in the Field of Precision Medicine
10.2 Challenges of EEs in the Field of Precision Medicine
10.2.1 Lack of Consistent Methods for Conducting Economic Evaluations
10.2.1.1 Enrichment Design
10.2.1.2 Randomized All Designs
10.2.1.3 Basket Clinical Trial
10.2.1.4 Umbrella Trials
10.2.2 Measuring the Real Value of Personalized Medicine
10.2.2.1 Willingness to Pay
10.2.2.2 Benefits Beyond the Health-Related Quality of Life
Capability Theory
Process Utility
Personal Utility
10.2.3 Inadequate Available Data
10.2.4 Increasing Complexity of EEs of PMI
10.2.4.1 Study Question
10.2.4.2 Sensitivity/Specificity and Predictive Value of the Test
10.2.4.3 Cascading Decision in EE of PMI
References
11: Ethical, Legal and Social Aspects of Precision Medicine
11.1 Ethical, Social, and Legal Aspects of PM: Research and Healthcare Context
11.2 Data Sharing: Clinical Care and Research
11.3 Patient Recruitment
11.4 Informed Consent (IC)
11.5 Pediatric Informed Consent
11.6 Unsolicited or “Incidental” Findings
11.7 Genetic Service and Biobanks
11.8 Institutional Review Boards (IRB)
11.9 The General Data Protection Regulation (GDPR) and Related Definitions
11.10 Reidentification and Pseudonymization
11.11 Blockchain
11.12 Personal Data
11.13 International Transfers of Personal Data: Regulation (EU) 2018/1725
11.14 Equal Access to Personalized Care
11.15 National Strategy or National Plan on Personalized Medicine
11.16 Examples of International Networks Working on Sharing Data
11.17 Intellectual Property of PM
11.18 Health Technology Assessment (HTA)
11.19 Patient Empowerment/Involvement
11.20 Incentives: Consideration
11.21 Direct-to-Consumer Genetic Testing
11.22 Work and Genetic Discrimination
11.23 Notes About Equity
11.24 ELSA Research Versus ELSA on PM Research
References
12: Personalized Medicine Literacy
12.1 Introduction
12.2 What Does Being Healthy Mean? The Determinants of Health During the Time
12.2.1 The Determinants of Health and Precision Cardiology
12.2.2 The Determinants of Health and Precision Oncology
12.2.3 The Determinants of Health and Precision Diabetology
12.2.4 COVID-19 Pandemic and the Social and Behavioral Innovations
12.3 The Role of Attitudes and Perceptions Assessment for Influencing Pro-health Behavior of the Citizens: Two Case Studies on Cancer Literacy and Vaccination Literacy
12.3.1 Cancer Literacy in Romania
12.3.1.1 Cancer Burden in Romania
12.3.2 Attitudes, Perceptions, and Behaviors on Cancer: National Survey (2016, 2018, 2020) in the Romanian Population
12.3.2.1 Fatalism
12.3.2.2 Personalized Medicine and Cancer Innovation Awareness
12.3.2.3 Quality of the Cancer Information Campaigns: From One-Size-Fits-All to Personalized Communication
12.3.3 Vaccination Literacy in Romania
12.3.3.1 HPV Vaccination Literacy
Two Sides of the Story About HPV Vaccination Efforts in Romania
12.3.3.2 COVID-19 Vaccination Literacy
12.4 Conclusions and Discussions
12.4.1 Future Perspectives on Increasing the Individual Level of Health Literacy by Periodically Assessing Attitudes, Perceptions, and Behaviors, in Synergy with the European Opportunities
References
13: Precision Medicine in Infectious Disease
13.1 Addressing Personalized Medicine Approaches on Infectious Diseases: Prevention, Diagnostic, and Treatment
13.2 Rapid Point-of-Care Diagnostics (POC-Ds) and Their Integration to Decision-Making in General Practice
13.3 Bacterial Infections
13.3.1 Climate Change-Related Infectious Disease
13.3.2 Tuberculosis Diseases (TB)
13.4 Viral Diseases: Zika and HIV Diseases
13.4.1 Zika Diseases
13.4.2 Human Immunodeficiency Virus (HIV)
13.5 Innovation Technologies: CRISPR/Cas9 and by CART (Chimeric Antigen Receptor T Cell)
13.5.1 Neglected Infectious Diseases (NIDs)
13.6 Malaria
13.7 Antimicrobial Resistance Diseases
13.8 Personalized Epidemiology
13.9 Vaccination Strategy
13.10 Microbiome
13.11 Coronaviruses
13.11.1 Introduction
13.12 SARS-CoV-2 Genome
13.13 Variations in SARS-CoV-2 Genome
13.14 Genomics of Host Susceptibility to COVID-19
13.15 Proposed Targets of Repurposed and Investigational Therapies for COVID-19
13.16 Precision Medicine and Pharmacogenomics Approach for COVID-19
13.17 Pharmacogenomics Aspect in COVID-19 Treatment Approach
13.17.1 Hydroxychloroquine and Chloroquine
13.18 Remdesivir
13.19 Viral Protease Inhibitors (Lopinavir, Ritonavir, Atazanavir, Oseltamivir)
13.20 Antimicrobial (Azithromycin)
13.21 Corticosteroids
13.22 RNA-Dependent RNA Polymerase
13.23 Conclusion
References