File #2681: "2019_Book_PersonalizedMedicineInHealthca.pdf"
Testo
1|Preface|6
1|Contents|8
1|Part I: Introduction|11
2|Options for Realising and Financing Innovation in the German Healthcare System|12
3|1 Introduction|12
3|2 Options for Financing the Introduction of Innovations in the German Healthcare System|14
4|2.1 Benefit Assessment by the Federal Joint Committee Upon Integration Into the Standard Care Offered by Statutory Health Insu...|14
4|2.2 Establishment of Innovations by Means of Regulations in Selective Contracts with Statutory Health Insurance Funds (Block I...|16
4|2.3 Fast Entry Options for Innovations Via Private Insurance or Direct Financing (Block III in Fig. 1)|17
3|3 Pricing When Implementing Innovations in Care|18
4|3.1 Pricing Based on the Benefit-in-Kind Principle of Statutory Health Insurance|19
5|3.1.1 Pharmaceuticals Focus 1: What Price Is Appropriate for a Medicinal Product in Germany?|21
5|3.1.2 Pharmaceuticals Focus 2: Lack of Pricing Regulation for Pharmaceutical Innovations in Germany|24
4|3.2 Price Setting by Health Insurance Funds and Service Providers Through Selective Contracts|25
4|3.3 Pricing Based on the Reimbursement Principle of Private Health Insurance and for Services Paid Directly|26
3|4 Final Observation|27
3|References|28
2|Clinical Evaluation of Medical Devices in Europe|30
3|1 Introduction|30
3|2 Results and Discussion|31
4|2.1 Regulatory Sphere|31
4|2.2 Classification of a Medical Device|34
4|2.3 Clinical Evaluation of the Medical Device|36
4|2.4 Documentation and Scrutiny Procedures|38
4|2.5 Post-Market Clinical Follow-Up (PMCF)|39
4|2.6 Recertification|40
3|References|41
2|Personalized Medicine: Cutting Edge Developments|42
3|1 Introduction|42
3|2 Molecular Dimension|43
3|3 Functional-Anatomical Dimension of Individualization|45
3|4 Tailored Medicine|46
3|5 Big Data|47
3|References|48
1|Part II: Methodological and Technological Aspects Important for Personalised Medicine|52
2|Nanotechnology Approaches for Autologous Stem Cell Manipulation in Personalized Regenerative Medicine|53
3|1 Introduction|53
3|2 Discovery of the Induced Pluripotent Stem Cells (iPSCs)|54
3|3 Problems in iPSCs Production and Risks in Their Clinical Application|55
3|4 Nanotechnology in iPSCs Reprogramming|57
3|5 Large Scale Amplification of Stem Cells Using Nanosubstrates|58
3|6 Directing iPSCs Differentiation Using Nanosubstrates|59
3|7 Conclusion|60
3|References|60
2|Patient-Doctor Relationship: Data Protection in the Context of Personalised Medicine|63
3|1 Introduction|63
3|2 Patient-Doctor Relationship: Personal Data Protection in the Context of Personalised Medicine|65
3|3 Personal Data Protection in the Decisions of the Court of Justice of the EU|65
3|4 Regulatory Framework|67
3|5 Interconnection of Health Systems|70
3|6 European Health Record and Data Protection Issues|71
3|7 Conclusion|72
3|References|73
2|High-Throughput Analytics in the Function of Personalized Medicine|74
3|1 Introduction|75
3|2 Development and Introduction of High-Throughput Methods in Analytical Biotechnology and Clinical Chemistry|77
3|3 Recent Progress in the Application of Newly Developed Materials for High-Throughput Detection|82
3|4 Biosensors: Development, Use and Strategies|83
4|4.1 Current Perspectives in Biosensor Development|85
4|4.2 Nanobiosensors|87
3|5 Conclusions|89
3|References|90
2|Bacteria-Human Interactions: Leads for Personalized Medicine|95
3|1 Introduction to the Human Microbiome|95
3|2 The Gut-Brain Axis: The Microbiome Is Important for Healthy Brain Function|97
3|3 Clinical Microbiology|99
3|4 Individuality of Bacterial Responses to Antibacterials|100
3|5 Antibacterials as a Possible Treatment for Modic Changes Type 1 and Lower Back Pain|101
3|6 Conclusion|102
3|References|102
2|Present and Future in Personalized Clinical and Laboratory Approaches to In Vitro Fertilization Procedures|105
3|1 Introduction|105
3|2 The Strategies of the Controlled Ovarian Stimulation (COS) and Treatment Approach Using Biomarkers|106
3|3 Embryo Quality Assessment Based on OMICS Methods and Research of the Oocyte Microenvironment|107
3|4 Screening of Biopsied Embryo|109
3|5 Conclusion|110
3|References|110
2|Microbiota: Novel Gateway Towards Personalised Medicine|112
3|1 Introduction|112
3|2 Normal Microbiota and Factors Affecting It|113
3|3 Microbiota and Disease|116
3|4 Microbiota as Cure|118
3|References|121
2|The Right Not to Know in the Context of Genetic Testing|126
3|1 Introduction|126
3|2 The Right to Informational Self-Determination|127
3|3 A Short History of the Right Not to Know|128
3|4 Legal Sources of the Right Not to Know|128
4|4.1 International Documents|128
4|4.2 German Domestic Sources|129
3|5 Genetic Testing, Personalised Medicine and the Right Not to Know|130
4|5.1 Information, Consent and Genetic Counselling|131
4|5.2 Interpretation of Genetic Data|132
4|5.3 Incidental Findings|132
5|5.3.1 Genetic Relatives|134
5|5.3.2 Making Test Results Public|135
5|5.3.3 Direct-to-Consumer Tests|136
3|6 Non-Observance of the Test Person´s Right Not to Know|137
3|7 Conclusion|138
3|References|138
3|Position Papers, Statements, Documents|138
3|Select Bibliography|139
1|Part III: Social and Humanistic Aspects of Personal Medicine|140
2|Personalized Medicine, Justice and Equality|141
3|1 Introduction|142
3|2 Sustainability of Health Care Systems and Questions of Justice|143
3|3 Fair Public Deliberation|144
3|4 The Strong Priority of Life Prolonging Therapies|146
3|5 Conclusion|151
3|References|151
2|Evolution Paths of Business Models in Personalized Medicine|152
3|1 Introduction|152
3|2 A Multidirectional Approach to Personalized Medicine and Economic Implications|154
3|3 Mapping the System|155
3|4 Shifting Power Position Through Regulation and Incentives|158
3|5 Conclusion|159
3|References|160
2|Socio-Humanistic and Political Context of Personalized Medicine|162
3|1 Expectations, Challenges|163
3|2 Dealing with Different Types of Society and Culture|164
3|3 Personalized Medicine and Education|164
3|4 Ethical and Legal Questions|165
3|5 Personalized Medicine and the Complexity of the Modern Society|166
3|6 Relationship Doctor: Patient as a Complete Human Being|167
3|7 Humanistic Context|169
3|8 The Role and Responsibility of Politics|169
3|9 Instead of a Conclusion|171
3|References|171
2|Personalized Medicine and Personalized Pricing: Degrees of Price Discrimination|173
3|1 Introduction|174
3|2 From Personalized Medicine to Personalized Pricing|175
3|3 Degrees of Price Discrimination|177
4|3.1 Price Discrimination of the First Degree|178
4|3.2 Price Discrimination of the Second Degree|178
4|3.3 Price Discrimination of the Third Degree|179
4|3.4 Price Discrimination of the Fourth Degree|180
3|4 Conclusion|181
3|References|182
2|Personalised Medicine in Health Care Systems and EU Law: The Role of Solidarity?|183
3|1 Introduction|183
3|2 EU Competences in the Field of Public Health|184
3|3 EU Approach to Personalised Medicine|186
3|4 The Importance of Health Technology Assessment in Personalised Medicine|188
3|5 HTA System in Croatia|191
3|6 The Role of Solidarity in Health Technology Assessment|193
3|7 Concluding Remarks|195
3|References|196
2|Personalizing Privacy? Examining the Shifting Boundaries of a Fundamental Right in Preimplantation Genetic Testing of Embryos|198
3|1 Introduction|198
3|2 Preimplantation Genetic Testing as a Challenge to the Boundaries of Bodily Privacy|199
3|3 Porous Constitutional Boundaries of Preimplantation Genetic Testing in the United States|202
3|4 National and Supranational Mediation Between Privacy and Preimplantation Genetic Testing in Europe|205
3|5 Conclusion|208
3|References|209
2|(Bio)ethical Aspects of Personalised Medicine: Revealing an ``Inconvenient Truth´´?|211
3|1 Introduction|211
3|2 Personalised Medicine: A Short Historical Insight|212
3|3 At the Crossroad of Medical Ethics and Bioethics|213
3|4 Conclusion|215
3|References|216
2|Patient-Physician Relationship in Personalized Medicine|217
3|1 Introduction|218
3|2 Alternations in the Nature of the Relationship|219
3|3 Factors That Influence Communication and the Relationship|219
3|4 What Can Challenge the Relationship?|221
3|5 The Relationship Participants´ Education in the Context of Personalized Medicine|223
3|6 Relationship in the Context of ``New Medicine´´|224
3|References|226
2|Barriers Towards New Medicine: Personalized and Integrative Medicine Concepts|227
3|1 Introduction|227
3|2 Holistic Medicine in a New Way|229
3|3 Current Conventional Medicine Major Pitfalls|233
3|4 Personalized Medicine Within the Integrative Medicine Paradigm|233
3|5 Conclusions|236
3|References|238
2|The Reverse Payment Settlements in the European Pharmaceutical Market|240
3|1 Introductory Remarks|240
3|2 Defining Reverse Payment Settlements|243
4|2.1 Decisions of the European Commission|246
3|3 Conclusion|250
3|References|251
2|Doping in Sports: Legal and Other Aspects|253
3|1 Introduction|253
3|2 Sports Act and Anti-Doping|256
3|3 Criminal Offences Interesting for the Sports Sector: Doping|256
3|4 NOC of Croatia and Anti-Doping|259
3|5 The Croatian Sports Arbitration Council and Anti-Doping|260
3|6 Croatian Football Federation´s Regulations|260
3|7 Case-Law on Doping|262
3|8 Conclusion|265
3|References|266
2|Personalised Medicine in Public Healthcare Systems|267
3|1 Definition of Personalised Medicine|267
3|2 The Main Characteristics of Public Healthcare Systems|269
3|3 Co-dependence of Personalised Medicine and Public Healthcare Systems|271
3|4 Conclusions|277
3|References|278
1|Part IV: Clinical Aspects of Personalised Medicine|280
2|Targeted Breast Cancer Therapy|281
3|1 Introduction|281
3|2 Trastuzumab in Adjuvant Therapy for Breast Cancer|282
3|3 Trastuzumab in Treatment of Metastatic Breast Cancer|283
3|4 Trastuzumab in Neo-Adjuvant Therapy for Breast Cancer|284
3|5 Trastuzumab in Combination with Other Biological Agents|284
3|6 Pertuzumab|285
3|7 Trastuzumab-Emtansine (T-DM1)|286
3|8 Bevacizumab|287
3|9 Conclusion|287
3|References|288
2|Personalized Medicine in Ophthalmology: Treatment of Total Limbal Stem Cell Deficiency with Autologous Ex Vivo Cultivated Limb...|291
3|1 Introduction|292
3|2 Cornea and Limbal Epithelial Stem Cells|292
3|3 Cultivation of LESC in Croatian Tissue Bank|295
3|4 Clinical Application of Ex Vivo Expanded Epithelial Cells|297
3|5 Conclusion|299
3|References|299
2|Personalized Total Knee Arthroplasty: Better Fit for Better Function|302
3|1 Brief History of Total Knee Arthroplasty|302
3|2 Anatomy of the Human Knee and Its Relationship to Total Knee Arthroplasty|303
3|3 Conventional Knee Arthroplasty|304
3|4 New Technology in Achieving Personalized Knee Arthroplasty|306
3|5 Conclusion|307
3|References|307
2|Comprehensive Approach to Personalized Medicine into Chronic Musculoskeletal Diseases|310
3|1 Introduction|310
4|1.1 Why Do We Need a New Concept in Treatment of Chronic Skeleton Diseases?|312
3|2 ``BaR´´: Holistic Concept Based on the Principles of Personalized and Integrative Medicine|312
4|2.1 Why Is It Important and How Does It Work in Clinical Practice?|313
4|2.2 The Basic Principles Which Exercise Need to Meet|313
4|2.3 What Is ``TAE-DO´´?|314
4|2.4 What Are the Advantages of Tae-do Over Other Standard Exercises?|314
3|3 Nuclear Magnetic Resonance Therapy: MBST|315
4|3.1 Case 1|316
4|3.2 Case 2|316
3|4 Conclusion|317
3|References|318
2|Circadian Rhythms and Personalized Melanoma Therapy|321
3|1 Circadian Disruption and Skin Cancers|322
3|2 Circadian Rhythms and Melanoma|324
4|2.1 Genetic Alterations in Clock Genes Associated with Melanoma|326
3|3 Melanoma Therapy and Targeted Approach|327
4|3.1 Chronotherapy in Melanoma Patients|330
3|References|332
2|Genetic and Epigenetic Profiling in Personalized Medicine: Advances in Treatment of Acute Myeloid Leukemia|335
3|1 Introduction|336
3|2 Genetic Landscape of Acute Myeloid Leukemia|337
3|3 Pharmacogenomics and Drug Response|339
4|3.1 Cytarabine Pharmacogenomics|340
4|3.2 Anthracyclines Pharmacogenomics|341
3|4 Molecular Targeted Therapies and Current Drugs|342
4|4.1 Targeted Therapy in AML with Recurrent Translocations|342
4|4.2 FLT3 Mutations and FLT3 Inhibitors|344
4|4.3 RAS Mutations and Targeted Therapy|345
4|4.4 NPM1 Mutations and Targeted Therapy|346
4|4.5 Mutations in Epigenetic Regulator Genes and Epigenetically Targeted Therapy|348
5|4.5.1 IDH Mutations in AML and IDH-Targeted Therapy|351
5|4.5.2 TET2 Mutations and Targeted Therapy|352
5|4.5.3 DNMT3A Mutations and Targeted Therapy|353
3|5 Immunotherapy and Cell Therapy|354
4|5.1 Antibody-Based AML Therapy|354
4|5.2 Therapy Using Vaccination|355
4|5.3 Therapy Using Chimeric Antigen Receptor (CAR)-Engineered T Cells (CAR-T Cells)|356
4|5.4 Adoptive NK Cell Therapy in AML|357
3|6 Conclusions|358
3|References|359
2|The Future of Cartilage Repair|369
3|1 Introduction|370
3|2 Therapy|374
4|2.1 Pharmacologic Management|374
5|2.1.1 Non-Steroidal Anti-Inflammatory Drugs and Opioid Analgesics|374
5|2.1.2 Structure/Disease Modifying Osteoarthritic Drugs (S/DMOADs)|376
4|2.2 Growth Factors Treatment|377
4|2.3 Joint Injections|378
5|2.3.1 Use of Corticosteroids|378
5|2.3.2 Use of Hyaluronic Acid Injections|378
4|2.4 Arthroscopic Lavage and Debridement|379
4|2.5 Marrow Stimulation Techniques: Microfractures and Augmentation|380
4|2.6 Osteochondral Grafts|381
4|2.7 Cell-Based Products|382
5|2.7.1 Autologous Chondrocyte Implantation and Matrix-Associated Chondrocyte Implantation|382
5|2.7.2 Bone Marrow Mesenchymal Stem Cells|384
5|2.7.3 Autologous Microfragmented Fat Tissue with Adipose Tissue-Derived Mesenchymal Stem Cells|385
3|3 Imaging of the Articular Cartilage Repair|388
4|3.1 Delayed Gadolinium-Enhanced MR Imaging of Cartilage (dGEMRIC)|391
4|3.2 T2 Mapping|393
4|3.3 T1ρ Imaging|395
4|3.4 Sodium (23Na) Imaging|396
4|3.5 Diffusion-Weighted Imaging|396
4|3.6 Glycosaminoglycan CEST|397
3|References|398
1|Contents|8
1|Part I: Introduction|11
2|Options for Realising and Financing Innovation in the German Healthcare System|12
3|1 Introduction|12
3|2 Options for Financing the Introduction of Innovations in the German Healthcare System|14
4|2.1 Benefit Assessment by the Federal Joint Committee Upon Integration Into the Standard Care Offered by Statutory Health Insu...|14
4|2.2 Establishment of Innovations by Means of Regulations in Selective Contracts with Statutory Health Insurance Funds (Block I...|16
4|2.3 Fast Entry Options for Innovations Via Private Insurance or Direct Financing (Block III in Fig. 1)|17
3|3 Pricing When Implementing Innovations in Care|18
4|3.1 Pricing Based on the Benefit-in-Kind Principle of Statutory Health Insurance|19
5|3.1.1 Pharmaceuticals Focus 1: What Price Is Appropriate for a Medicinal Product in Germany?|21
5|3.1.2 Pharmaceuticals Focus 2: Lack of Pricing Regulation for Pharmaceutical Innovations in Germany|24
4|3.2 Price Setting by Health Insurance Funds and Service Providers Through Selective Contracts|25
4|3.3 Pricing Based on the Reimbursement Principle of Private Health Insurance and for Services Paid Directly|26
3|4 Final Observation|27
3|References|28
2|Clinical Evaluation of Medical Devices in Europe|30
3|1 Introduction|30
3|2 Results and Discussion|31
4|2.1 Regulatory Sphere|31
4|2.2 Classification of a Medical Device|34
4|2.3 Clinical Evaluation of the Medical Device|36
4|2.4 Documentation and Scrutiny Procedures|38
4|2.5 Post-Market Clinical Follow-Up (PMCF)|39
4|2.6 Recertification|40
3|References|41
2|Personalized Medicine: Cutting Edge Developments|42
3|1 Introduction|42
3|2 Molecular Dimension|43
3|3 Functional-Anatomical Dimension of Individualization|45
3|4 Tailored Medicine|46
3|5 Big Data|47
3|References|48
1|Part II: Methodological and Technological Aspects Important for Personalised Medicine|52
2|Nanotechnology Approaches for Autologous Stem Cell Manipulation in Personalized Regenerative Medicine|53
3|1 Introduction|53
3|2 Discovery of the Induced Pluripotent Stem Cells (iPSCs)|54
3|3 Problems in iPSCs Production and Risks in Their Clinical Application|55
3|4 Nanotechnology in iPSCs Reprogramming|57
3|5 Large Scale Amplification of Stem Cells Using Nanosubstrates|58
3|6 Directing iPSCs Differentiation Using Nanosubstrates|59
3|7 Conclusion|60
3|References|60
2|Patient-Doctor Relationship: Data Protection in the Context of Personalised Medicine|63
3|1 Introduction|63
3|2 Patient-Doctor Relationship: Personal Data Protection in the Context of Personalised Medicine|65
3|3 Personal Data Protection in the Decisions of the Court of Justice of the EU|65
3|4 Regulatory Framework|67
3|5 Interconnection of Health Systems|70
3|6 European Health Record and Data Protection Issues|71
3|7 Conclusion|72
3|References|73
2|High-Throughput Analytics in the Function of Personalized Medicine|74
3|1 Introduction|75
3|2 Development and Introduction of High-Throughput Methods in Analytical Biotechnology and Clinical Chemistry|77
3|3 Recent Progress in the Application of Newly Developed Materials for High-Throughput Detection|82
3|4 Biosensors: Development, Use and Strategies|83
4|4.1 Current Perspectives in Biosensor Development|85
4|4.2 Nanobiosensors|87
3|5 Conclusions|89
3|References|90
2|Bacteria-Human Interactions: Leads for Personalized Medicine|95
3|1 Introduction to the Human Microbiome|95
3|2 The Gut-Brain Axis: The Microbiome Is Important for Healthy Brain Function|97
3|3 Clinical Microbiology|99
3|4 Individuality of Bacterial Responses to Antibacterials|100
3|5 Antibacterials as a Possible Treatment for Modic Changes Type 1 and Lower Back Pain|101
3|6 Conclusion|102
3|References|102
2|Present and Future in Personalized Clinical and Laboratory Approaches to In Vitro Fertilization Procedures|105
3|1 Introduction|105
3|2 The Strategies of the Controlled Ovarian Stimulation (COS) and Treatment Approach Using Biomarkers|106
3|3 Embryo Quality Assessment Based on OMICS Methods and Research of the Oocyte Microenvironment|107
3|4 Screening of Biopsied Embryo|109
3|5 Conclusion|110
3|References|110
2|Microbiota: Novel Gateway Towards Personalised Medicine|112
3|1 Introduction|112
3|2 Normal Microbiota and Factors Affecting It|113
3|3 Microbiota and Disease|116
3|4 Microbiota as Cure|118
3|References|121
2|The Right Not to Know in the Context of Genetic Testing|126
3|1 Introduction|126
3|2 The Right to Informational Self-Determination|127
3|3 A Short History of the Right Not to Know|128
3|4 Legal Sources of the Right Not to Know|128
4|4.1 International Documents|128
4|4.2 German Domestic Sources|129
3|5 Genetic Testing, Personalised Medicine and the Right Not to Know|130
4|5.1 Information, Consent and Genetic Counselling|131
4|5.2 Interpretation of Genetic Data|132
4|5.3 Incidental Findings|132
5|5.3.1 Genetic Relatives|134
5|5.3.2 Making Test Results Public|135
5|5.3.3 Direct-to-Consumer Tests|136
3|6 Non-Observance of the Test Person´s Right Not to Know|137
3|7 Conclusion|138
3|References|138
3|Position Papers, Statements, Documents|138
3|Select Bibliography|139
1|Part III: Social and Humanistic Aspects of Personal Medicine|140
2|Personalized Medicine, Justice and Equality|141
3|1 Introduction|142
3|2 Sustainability of Health Care Systems and Questions of Justice|143
3|3 Fair Public Deliberation|144
3|4 The Strong Priority of Life Prolonging Therapies|146
3|5 Conclusion|151
3|References|151
2|Evolution Paths of Business Models in Personalized Medicine|152
3|1 Introduction|152
3|2 A Multidirectional Approach to Personalized Medicine and Economic Implications|154
3|3 Mapping the System|155
3|4 Shifting Power Position Through Regulation and Incentives|158
3|5 Conclusion|159
3|References|160
2|Socio-Humanistic and Political Context of Personalized Medicine|162
3|1 Expectations, Challenges|163
3|2 Dealing with Different Types of Society and Culture|164
3|3 Personalized Medicine and Education|164
3|4 Ethical and Legal Questions|165
3|5 Personalized Medicine and the Complexity of the Modern Society|166
3|6 Relationship Doctor: Patient as a Complete Human Being|167
3|7 Humanistic Context|169
3|8 The Role and Responsibility of Politics|169
3|9 Instead of a Conclusion|171
3|References|171
2|Personalized Medicine and Personalized Pricing: Degrees of Price Discrimination|173
3|1 Introduction|174
3|2 From Personalized Medicine to Personalized Pricing|175
3|3 Degrees of Price Discrimination|177
4|3.1 Price Discrimination of the First Degree|178
4|3.2 Price Discrimination of the Second Degree|178
4|3.3 Price Discrimination of the Third Degree|179
4|3.4 Price Discrimination of the Fourth Degree|180
3|4 Conclusion|181
3|References|182
2|Personalised Medicine in Health Care Systems and EU Law: The Role of Solidarity?|183
3|1 Introduction|183
3|2 EU Competences in the Field of Public Health|184
3|3 EU Approach to Personalised Medicine|186
3|4 The Importance of Health Technology Assessment in Personalised Medicine|188
3|5 HTA System in Croatia|191
3|6 The Role of Solidarity in Health Technology Assessment|193
3|7 Concluding Remarks|195
3|References|196
2|Personalizing Privacy? Examining the Shifting Boundaries of a Fundamental Right in Preimplantation Genetic Testing of Embryos|198
3|1 Introduction|198
3|2 Preimplantation Genetic Testing as a Challenge to the Boundaries of Bodily Privacy|199
3|3 Porous Constitutional Boundaries of Preimplantation Genetic Testing in the United States|202
3|4 National and Supranational Mediation Between Privacy and Preimplantation Genetic Testing in Europe|205
3|5 Conclusion|208
3|References|209
2|(Bio)ethical Aspects of Personalised Medicine: Revealing an ``Inconvenient Truth´´?|211
3|1 Introduction|211
3|2 Personalised Medicine: A Short Historical Insight|212
3|3 At the Crossroad of Medical Ethics and Bioethics|213
3|4 Conclusion|215
3|References|216
2|Patient-Physician Relationship in Personalized Medicine|217
3|1 Introduction|218
3|2 Alternations in the Nature of the Relationship|219
3|3 Factors That Influence Communication and the Relationship|219
3|4 What Can Challenge the Relationship?|221
3|5 The Relationship Participants´ Education in the Context of Personalized Medicine|223
3|6 Relationship in the Context of ``New Medicine´´|224
3|References|226
2|Barriers Towards New Medicine: Personalized and Integrative Medicine Concepts|227
3|1 Introduction|227
3|2 Holistic Medicine in a New Way|229
3|3 Current Conventional Medicine Major Pitfalls|233
3|4 Personalized Medicine Within the Integrative Medicine Paradigm|233
3|5 Conclusions|236
3|References|238
2|The Reverse Payment Settlements in the European Pharmaceutical Market|240
3|1 Introductory Remarks|240
3|2 Defining Reverse Payment Settlements|243
4|2.1 Decisions of the European Commission|246
3|3 Conclusion|250
3|References|251
2|Doping in Sports: Legal and Other Aspects|253
3|1 Introduction|253
3|2 Sports Act and Anti-Doping|256
3|3 Criminal Offences Interesting for the Sports Sector: Doping|256
3|4 NOC of Croatia and Anti-Doping|259
3|5 The Croatian Sports Arbitration Council and Anti-Doping|260
3|6 Croatian Football Federation´s Regulations|260
3|7 Case-Law on Doping|262
3|8 Conclusion|265
3|References|266
2|Personalised Medicine in Public Healthcare Systems|267
3|1 Definition of Personalised Medicine|267
3|2 The Main Characteristics of Public Healthcare Systems|269
3|3 Co-dependence of Personalised Medicine and Public Healthcare Systems|271
3|4 Conclusions|277
3|References|278
1|Part IV: Clinical Aspects of Personalised Medicine|280
2|Targeted Breast Cancer Therapy|281
3|1 Introduction|281
3|2 Trastuzumab in Adjuvant Therapy for Breast Cancer|282
3|3 Trastuzumab in Treatment of Metastatic Breast Cancer|283
3|4 Trastuzumab in Neo-Adjuvant Therapy for Breast Cancer|284
3|5 Trastuzumab in Combination with Other Biological Agents|284
3|6 Pertuzumab|285
3|7 Trastuzumab-Emtansine (T-DM1)|286
3|8 Bevacizumab|287
3|9 Conclusion|287
3|References|288
2|Personalized Medicine in Ophthalmology: Treatment of Total Limbal Stem Cell Deficiency with Autologous Ex Vivo Cultivated Limb...|291
3|1 Introduction|292
3|2 Cornea and Limbal Epithelial Stem Cells|292
3|3 Cultivation of LESC in Croatian Tissue Bank|295
3|4 Clinical Application of Ex Vivo Expanded Epithelial Cells|297
3|5 Conclusion|299
3|References|299
2|Personalized Total Knee Arthroplasty: Better Fit for Better Function|302
3|1 Brief History of Total Knee Arthroplasty|302
3|2 Anatomy of the Human Knee and Its Relationship to Total Knee Arthroplasty|303
3|3 Conventional Knee Arthroplasty|304
3|4 New Technology in Achieving Personalized Knee Arthroplasty|306
3|5 Conclusion|307
3|References|307
2|Comprehensive Approach to Personalized Medicine into Chronic Musculoskeletal Diseases|310
3|1 Introduction|310
4|1.1 Why Do We Need a New Concept in Treatment of Chronic Skeleton Diseases?|312
3|2 ``BaR´´: Holistic Concept Based on the Principles of Personalized and Integrative Medicine|312
4|2.1 Why Is It Important and How Does It Work in Clinical Practice?|313
4|2.2 The Basic Principles Which Exercise Need to Meet|313
4|2.3 What Is ``TAE-DO´´?|314
4|2.4 What Are the Advantages of Tae-do Over Other Standard Exercises?|314
3|3 Nuclear Magnetic Resonance Therapy: MBST|315
4|3.1 Case 1|316
4|3.2 Case 2|316
3|4 Conclusion|317
3|References|318
2|Circadian Rhythms and Personalized Melanoma Therapy|321
3|1 Circadian Disruption and Skin Cancers|322
3|2 Circadian Rhythms and Melanoma|324
4|2.1 Genetic Alterations in Clock Genes Associated with Melanoma|326
3|3 Melanoma Therapy and Targeted Approach|327
4|3.1 Chronotherapy in Melanoma Patients|330
3|References|332
2|Genetic and Epigenetic Profiling in Personalized Medicine: Advances in Treatment of Acute Myeloid Leukemia|335
3|1 Introduction|336
3|2 Genetic Landscape of Acute Myeloid Leukemia|337
3|3 Pharmacogenomics and Drug Response|339
4|3.1 Cytarabine Pharmacogenomics|340
4|3.2 Anthracyclines Pharmacogenomics|341
3|4 Molecular Targeted Therapies and Current Drugs|342
4|4.1 Targeted Therapy in AML with Recurrent Translocations|342
4|4.2 FLT3 Mutations and FLT3 Inhibitors|344
4|4.3 RAS Mutations and Targeted Therapy|345
4|4.4 NPM1 Mutations and Targeted Therapy|346
4|4.5 Mutations in Epigenetic Regulator Genes and Epigenetically Targeted Therapy|348
5|4.5.1 IDH Mutations in AML and IDH-Targeted Therapy|351
5|4.5.2 TET2 Mutations and Targeted Therapy|352
5|4.5.3 DNMT3A Mutations and Targeted Therapy|353
3|5 Immunotherapy and Cell Therapy|354
4|5.1 Antibody-Based AML Therapy|354
4|5.2 Therapy Using Vaccination|355
4|5.3 Therapy Using Chimeric Antigen Receptor (CAR)-Engineered T Cells (CAR-T Cells)|356
4|5.4 Adoptive NK Cell Therapy in AML|357
3|6 Conclusions|358
3|References|359
2|The Future of Cartilage Repair|369
3|1 Introduction|370
3|2 Therapy|374
4|2.1 Pharmacologic Management|374
5|2.1.1 Non-Steroidal Anti-Inflammatory Drugs and Opioid Analgesics|374
5|2.1.2 Structure/Disease Modifying Osteoarthritic Drugs (S/DMOADs)|376
4|2.2 Growth Factors Treatment|377
4|2.3 Joint Injections|378
5|2.3.1 Use of Corticosteroids|378
5|2.3.2 Use of Hyaluronic Acid Injections|378
4|2.4 Arthroscopic Lavage and Debridement|379
4|2.5 Marrow Stimulation Techniques: Microfractures and Augmentation|380
4|2.6 Osteochondral Grafts|381
4|2.7 Cell-Based Products|382
5|2.7.1 Autologous Chondrocyte Implantation and Matrix-Associated Chondrocyte Implantation|382
5|2.7.2 Bone Marrow Mesenchymal Stem Cells|384
5|2.7.3 Autologous Microfragmented Fat Tissue with Adipose Tissue-Derived Mesenchymal Stem Cells|385
3|3 Imaging of the Articular Cartilage Repair|388
4|3.1 Delayed Gadolinium-Enhanced MR Imaging of Cartilage (dGEMRIC)|391
4|3.2 T2 Mapping|393
4|3.3 T1ρ Imaging|395
4|3.4 Sodium (23Na) Imaging|396
4|3.5 Diffusion-Weighted Imaging|396
4|3.6 Glycosaminoglycan CEST|397
3|References|398