http://www.mdpi.com/journal/jpm Latest open access articles published in J. Pers. Med. at http://www.mdpi.com/journal/jpm http://www.mdpi.com/2075-4426/3/2/111 We surveyed 10,303 United States physicians on where they obtain pharmacogenomic testing information. Thirty-nine percent indicated that they obtained this from drug labeling. Factors positively associated with this response included older age, postgraduate instruction, using other information sources, regulatory approval/ recommendation of testing, reliance on labeling for information, and perception that patients have benefited from testing. Physicians use pharmacogenomic testing information from drug labeling, highlighting the importance of labeling information that is conducive to practice application. Journal of Personalized Medicine 2013-06-10 3 2 Article 10.3390/jpm3020111 111 123 2075-4426 2013-06-10 doi: 10.3390/jpm3020111 Eric Stanek Christopher Sanders Felix Frueh http://www.mdpi.com/2075-4426/3/2/102 One of the most significant impediments to the current goals of genomic research is the limited availability of high quality biological samples. Despite efforts to increase both the quality and quantity of samples collected, access to such samples remains limited. This may be due, at least in part, to a general reluctance of biobanking professionals, clinicians, and researchers to share biological specimens with others. Ethnographic methods were used in a biobank setting to explore professionals’ perspectives toward and practices of sharing samples. Several motivations and barriers to sharing that may influence research practice were identified. Contrary to existing literature that suggests that professionals are unlikely to share samples with one another, the participants of this study were open to and supportive of sharing samples for research. However, clear communication and effective infrastructure are needed to support the distribution of biobank materials. Journal of Personalized Medicine 2013-06-06 3 2 Article 10.3390/jpm3020102 102 110 2075-4426 2013-06-06 doi: 10.3390/jpm3020102 Stacey Pereira http://www.mdpi.com/2075-4426/3/2/82 The Arterial Pressure Waveform (APW) can provide essential information about arterial wall integrity and arterial stiffness. Most of APW analysis frameworks individually process each hemodynamic parameter and do not evaluate inter-dependencies in the overall pulse morphology. The key contribution of this work is the use of machine learning algorithms to deal with vectorized features extracted from APW. With this purpose, we follow a five-step evaluation methodology: (1) a custom-designed, non-invasive, electromechanical device was used in the data collection from 50 subjects; (2) the acquired position and amplitude of onset, Systolic Peak (SP), Point of Inflection (Pi) and Dicrotic Wave (DW) were used for the computation of some morphological attributes; (3) pre-processing work on the datasets was performed in order to reduce the number of input features and increase the model accuracy by selecting the most relevant ones; (4) classification of the dataset was carried out using four different machine learning algorithms: Random Forest, BayesNet (probabilistic), J48 (decision tree) and RIPPER (rule-based induction); and (5) we evaluate the trained models, using the majority-voting system, comparatively to the respective calculated Augmentation Index (AIx). Classification algorithms have been proved to be efficient, in particular Random Forest has shown good accuracy (96.95%) and high area under the curve (AUC) of a Receiver Operating Characteristic (ROC) curve (0.961). Finally, during validation tests, a correlation between high risk labels, retrieved from the multi-parametric approach, and positive AIx values was verified. This approach gives allowance for designing new hemodynamic morphology vectors and techniques for multiple APW analysis, thus improving the arterial pulse understanding, especially when compared to traditional single-parameter analysis, where the failure in one parameter measurement component, such as Pi, can jeopardize the whole evaluation. Journal of Personalized Medicine 2013-05-02 3 2 Article 10.3390/jpm3020082 82 101 2075-4426 2013-05-02 doi: 10.3390/jpm3020082 Vânia Almeida João Vieira Pedro Santos Tânia Pereira H. Pereira Carlos Correia Mariano Pego João Cardoso http://www.mdpi.com/2075-4426/3/2/70 The Oslo University Hospital (Norway), the K.G. Jebsen Centre for Breast Cancer Research (Norway), The Radiumhospital Foundation (Norway) and the Fritz-Bender-Foundation (Germany) designed under the conference chairmen (E. Mihich, K.S. Zänker, A.L. Borresen-Dale) and advisory committee (A. Borg, Z. Szallasi, O. Kallioniemi, H.P. Huber) a program at the cutting edge of “PERSONALIZED CANCER CARE: Risk prediction, early diagnosis, progression and therapy resistance.” The conference was held in Oslo from September 7 to 9, 2012 and the science-based presentations concerned six scientific areas: (1) Genetic profiling of patients, prediction of risk, late side effects; (2) Molecular profiling of tumors and metastases; (3) Tumor-host microenvironment interaction and metabolism; (4) Targeted therapy; (5) Translation and (6) Informed consent, ethical challenges and communication. Two satellite workshops on (i) Ion Ampliseq—a novel tool for large scale mutation detection; and (ii) Multiplex RNA ISH and tissue homogenate assays for cancer biomarker validation were additionally organized. The report concludes that individual risk prediction in carcinogenesis and/or metastatogenesis based on polygenic profiling may be useful for intervention strategies for health care and therapy planning in the future. To detect distinct and overlapping DNA sequence alterations in tumor samples and adjacent normal tissues, including point mutations, small insertions or deletions, copy number changes and chromosomal rearrangements will eventually make it possible to design personalized management plans for individualized patients. However, large individualized datasets need a new approach in bio-information technology to reduce this enormous data dimensionally to simply working hypotheses about health and disease for each individual. Journal of Personalized Medicine 2013-04-29 3 2 Meeting Report 10.3390/jpm3020070 70 81 2075-4426 2013-04-29 doi: 10.3390/jpm3020070 Kurt Zänker Enrico Mihich Hans-Peter Huber Anne-Lise Borresen-Dale http://www.mdpi.com/2075-4426/3/1/40 Rapid progress in genomics and nanotechnology continue to advance our approach to patient care, from diagnosis and prognosis, to targeting and personalization of therapeutics. However, the clinical application of molecular diagnostics in ophthalmology has been limited even though there have been demonstrations of disease risk and pharmacogenetic associations. There is a high clinical need for therapeutic personalization and dosage optimization in ophthalmology and may be the focus of individualized medicine in this specialty. In several retinal conditions, such as age-related macular degeneration, diabetic macular edema, retinal vein occlusion and pre-threshold retinopathy of prematurity, anti-vascular endothelial growth factor therapeutics have resulted in enhanced outcomes. In glaucoma, recent advances in cytoskeletal agents and prostaglandin molecules that affect outflow and remodel the trabecular meshwork have demonstrated improved intraocular pressure control. Application of recent developments in nanoemulsion and polymeric micelle for targeted delivery and drug release are models of dosage optimization, increasing efficacy and improving outcomes in these major eye diseases. Journal of Personalized Medicine 2013-03-05 3 1 Review 10.3390/jpm3010040 40 69 2075-4426 2013-03-05 doi: 10.3390/jpm3010040 Frank Ong Jane Kuo Wei-Chi Wu Ching-Yu Cheng Wendell-Lamar Blackwell Brian Taylor Wayne Grody Jerome Rotter Chi-Chun Lai Tien Wong http://www.mdpi.com/2075-4426/3/1/23 Sensors have become ubiquitous in their reach and scope of application. They are a technological cornerstone for various modes of health surveillance and participatory medicine—such as quantifying oneself; they are also employed to track people with certain as impairments perceived ability differences. This paper presents quantitative and qualitative data of an exploratory, non-generalizable study into the perceptions, attitudes and concerns of staff of a disability service organization, that mostly serve people with intellectual disabilities, towards the use of various types of sensor technologies that might be used by and with their clients. In addition, perspectives of various types of privacy issues linked to sensors, as well data regarding the concept of quantified self were obtained. Our results highlight the need to involve disabled people and their support networks in sensor and quantified-self discourses, in order to prevent undue disadvantages. Journal of Personalized Medicine 2013-02-22 3 1 Article 10.3390/jpm3010023 23 39 2075-4426 2013-02-22 doi: 10.3390/jpm3010023 Gregor Wolbring Verlyn Leopatra http://www.mdpi.com/2075-4426/3/1/14 Personalized medicine can be seen as a continuously developing approach to tailoring treatments according to the individual characteristics of a patient. In some way, medicine has always been personalized. During the last decade, however, scientific and technological progress have made truly personalized healthcare increasingly become reality. Today’s personalized medicine involves targeted therapies and diagnostic tests. The development of targeted agents represents a major investment opportunity to pharmaceutical companies, which have been facing the need to diversify their business due to an increasingly challenging market place. By investing into the development of personalized therapies, pharmaceutical companies mitigate a major part of the risks posed by factors such as patent expiries or generic competition. Viewing upon personalized medicine from different perspectives points out the multi-causality of its emergence. Research efforts and business diversification have been two main driving forces; they do supplement each other, however, are not jointly exhaustive in explaining the emergence of this approach. Especially in the future, a number of further stakeholders will impact the evolution of personalized medicine. Journal of Personalized Medicine 2013-01-17 3 1 Opinion 10.3390/jpm3010014 14 22 2075-4426 2013-01-17 doi: 10.3390/jpm3010014 Julius Steffen Jan Steffen http://www.mdpi.com/2075-4426/3/1/1 Cancer care is often inconsistently delivered with inadequate incorporation of patient values and objective evidence into decision-making. Utilization of time limited trials of care with predefined decision points that are based on iteratively updated best evidence, tools that inform providers about a patient’s experience and values, and known information about a patient’s disease will allow superior matched care to be delivered. Personalized medicine does not merely refer to the incorporation of genetic information into clinical care, it involves utilization of the wide array of data points relevant to care, many of which are readily available at the bedside today. By pushing uptake of personalized matching available today, clinicians can better address the triple aim of improved health, lowers costs, and enhanced patient experience, and we can prepare the health care landscape for the iterative inclusion of progressively more sophisticated information as newer tests and information become available to support the personalized medicine paradigm. Journal of Personalized Medicine 2012-12-27 3 1 Review 10.3390/jpm3010001 1 13 2075-4426 2012-12-27 doi: 10.3390/jpm3010001 Bradford Hirsch Amy Abernethy http://www.mdpi.com/2075-4426/2/4/277 Pediatric patients exhibit their own needs and problems and are now considered as a real patient group in which downsizing the adult formulation is not the best choice and may result in problems. Adolescence (between 12 and 18 years) is a transitional period of life from puberty to adulthood and, in this pediatric subgroup population, complex problems are observed in compliance with chronic treatments. Heterogeneity exists in this group which follows very different and sometimes short trends and tendencies and where illness can be a problem leading to stigmatization. Influence of social environment as well as friends is complex in this period of life. Teenagers have to take care of themselves and be part of the treatment including all the features of the social code of this group. Particular attention has to be paid to formulation and packaging in order to increase compliance and to suit the specific needs of this pediatric subgroup. Some examples are given for different drug forms. Journal of Personalized Medicine 2012-12-11 2 4 Opinion 10.3390/jpm2040277 277 286 2075-4426 2012-12-11 doi: 10.3390/jpm2040277 Pascale Gauthier Jean-Michel Cardot http://www.mdpi.com/2075-4426/2/4/267 Deviations in execution from the prescribed drug intake schedules (timing non adherence) are frequent and may pose a substantial risk for therapeutic failure. Simple methods to monitor timing adherence with multiple drugs are missing. A new technology, i.e., the polymedication electronic monitoring system (POEMS) attached to a multidrug punch card, was used in a clinical trial on outpatients with prescribed medicines for vascular risk reduction. The complete delineation of timing adherence allows for the calculation of objective adherence parameters and the linking of exposure with drug-drug interactions. A sub-analysis was performed on 68 patients, who were prescribed lipid lowering therapy. A smaller intake time variability of the lipid lowering drug was significantly associated with better levels of LDL-cholesterol, independently of the time of day. This finding may challenge current general recommendations for the timing of lipid lowering drugs’ intake and substantiate that inter-individual differences in timing adherence may contribute to response variability. Thus, objective parameters based on multidrug adherence monitoring should be considered as independent variables in personalized medicine. In clinical practice, personalized intake recommendations according to patients’ pattern of timing adherence may help to optimize the effectiveness of lipid lowering agents. Journal of Personalized Medicine 2012-11-28 2 4 Article 10.3390/jpm2040267 267 276 2075-4426 2012-11-28 doi: 10.3390/jpm2040267 Philipp Walter Isabelle Arnet Michel Romanens Dimitrios Tsakiris Kurt Hersberger http://www.mdpi.com/2075-4426/2/4/257 The twin forces of payors seeking fair pricing and the rising costs of developing new medicines has driven a closer relationship between pharmaceutical companies and diagnostics companies, because stratified medicines, guided by companion diagnostics, offer better commercial, as well as clinical, outcomes. Stratified medicines have created clinical success and provided rapid product approvals, particularly in oncology, and indeed have changed the dynamic between drug and diagnostic developers. The commercial payback for such partnerships offered by stratified medicines has been less well articulated, but this has shifted as the benefits in risk management, pricing and value creation for all stakeholders become clearer. In this larger healthcare setting, stratified medicine provides both physicians and patients with greater insight on the disease and provides rationale for providers to understand cost-effectiveness of treatment. This article considers how the economic value of stratified medicine relationships can be recognized and translated into better outcomes for all healthcare stakeholders. Journal of Personalized Medicine 2012-11-26 2 4 Review 10.3390/jpm2040257 257 266 2075-4426 2012-11-26 doi: 10.3390/jpm2040257 Edward D. Blair Elyse K. Stratton Martina Kaufmann http://www.mdpi.com/2075-4426/2/4/241 Findings from pharmacogenomics (PGx) studies have the potential to be applied to individualize drug therapy to improve efficacy and reduce adverse drug events. Researchers have identified factors influencing uptake of genomics in medicine, but little is known about the specific technical barriers to incorporating PGx into existing clinical frameworks. We present the design and development of a prototype PGx clinical decision support (CDS) system that builds on existing clinical infrastructure and incorporates semi-active and active CDS. Informing this work, we updated previous evaluations of PGx knowledge characteristics, and of how the CDS capabilities of three local clinical systems align with data and functional requirements for PGx CDS. We summarize characteristics of PGx knowledge and technical needs for implementing PGx CDS within existing clinical frameworks. PGx decision support rules derived from FDA drug labels primarily involve drug metabolizing genes, vary in maturity, and the majority support the post-analytic phase of genetic testing. Computerized provider order entry capabilities are key functional requirements for PGx CDS and were best supported by one of the three systems we evaluated. We identified two technical needs when building on this system, the need for (1) new or existing standards for data exchange to connect clinical data to PGx knowledge, and (2) a method for implementing semi-active CDS. Our analyses enhance our understanding of principles for designing and implementing CDS for drug therapy individualization and our current understanding of PGx characteristics in a clinical context. Characteristics of PGx knowledge and capabilities of current clinical systems can help govern decisions about CDS implementation, and can help guide decisions made by groups that develop and maintain knowledge resources such that delivery of content for clinical care is supported. Journal of Personalized Medicine 2012-11-20 2 4 Article 10.3390/jpm2040241 241 256 2075-4426 2012-11-20 doi: 10.3390/jpm2040241 Casey Lynnette Overby Peter Tarczy-Hornoch Ira J. Kalet Kenneth E. Thummel Joe W. Smith Guilherme Del Fiol David Fenstermacher Emily Beth Devine http://www.mdpi.com/2075-4426/2/4/232 While the full promise of genomic medicine may be many years in the future, personalized health care (PHC) can begin solving important health care needs now and provide a framework for the adoption of genomic technologies as they are validated. PHC is a strategic approach to medicine that is individualized, predictive, preventive, and involves intense patient engagement. There is great need for more effective models of care as nearly half of Medicare patients age 65 and older have three or more preventable chronic conditions and account for 89% of Medicare’s growing expenditures. With its focus on reactive care, the current health care system is not designed to effectively prevent disease nor manage patients with multiple chronic conditions. PHC may be a solution for improving care for this population and therefore has been adopted as the delivery platform along with a new personalized health plan tool for 230 multi-morbid, homebound Medicare recipients in Durham, North Carolina who have been high utilizers of health care resources. PHC integrates available personalized health technologies, standards of care, and personalized health planning to serve as a model for rational health care delivery. Importantly, the PHC model of care will serve as a market for emerging predictive and personalized technologies to foster genomic medicine. Journal of Personalized Medicine 2012-11-13 2 4 Article 10.3390/jpm2040232 232 240 2075-4426 2012-11-13 doi: 10.3390/jpm2040232 Robin Burnette Leigh Simmons Ralph Snyderman http://www.mdpi.com/2075-4426/2/4/217 New devices enabling freely selectable dosing of solid oral medications are urgently needed for personalized medicine. One approach is the use of the recently published Solid Dosage Pen, allowing flexible dosing of tablet-like sustained release slices from drug loaded extruded strands. Slices were suitable for oral single dosed application. The aim of the present study was the development of immediate release dosage forms for applications of the device, especially for young children. Using two model drugs, two different concepts were investigated and evaluated. Effervescent formulations were manufactured by an organic wet-extrusion process and immediate release formulations by a melt-extrusion process. Dissolution experiments were performed for both formulations to ensure the immediate release behavior. Extruded strands were individually dosed by the Solid Dosage Pen. Various doses of the two formulations were analyzed regarding uniformity of mass and content according to pharmacopoeial specifications. Proof of concept was demonstrated in both approaches as results comply with the regulatory requirements. Furthermore, storing stress tests were performed and drug formulations were characterized after storing. The results show that suitable packaging material has been selected and storage stability is probable. Journal of Personalized Medicine 2012-11-06 2 4 Article 10.3390/jpm2040217 217 231 2075-4426 2012-11-06 doi: 10.3390/jpm2040217 Klaus Wening Eva Laukamp Markus Thommes Jörg Breitkreutz http://www.mdpi.com/2075-4426/2/4/201 Adoption of personalized medicine in practice has been slow, in part due to the lack of evidence of clinical benefit provided by these technologies. Coverage by insurers is a critical step in achieving widespread adoption of personalized medicine. Insurers consider a variety of factors when formulating medical coverage policies for personalized medicine, including the overall strength of evidence for a test, availability of clinical guidelines and health technology assessments by independent organizations. In this study, we reviewed coverage policies of the largest U.S. insurers for genomic (disease-related) and pharmacogenetic (PGx) tests to determine the extent that these tests were covered and the evidence basis for the coverage decisions. We identified 41 coverage policies for 49 unique testing: 22 tests for disease diagnosis, prognosis and risk and 27 PGx tests. Fifty percent (or less) of the tests reviewed were covered by insurers. Lack of evidence of clinical utility appears to be a major factor in decisions of non-coverage. The inclusion of PGx information in drug package inserts appears to be a common theme of PGx tests that are covered. This analysis highlights the variability of coverage determinations and factors considered, suggesting that the adoption of personal medicine will affected by numerous factors, but will continue to be slowed due to lack of demonstrated clinical benefit. Journal of Personalized Medicine 2012-10-30 2 4 Article 10.3390/jpm2040201 201 216 2075-4426 2012-10-30 doi: 10.3390/jpm2040201 Andrew Hresko Susanne B. Haga http://www.mdpi.com/2075-4426/2/4/192 Direct to consumer (DTC) genomic services facilitate the personalized and participatory aspects of “P4” medicine, but raise questions regarding use of genomic data in providing predictive and preventive healthcare. We illustrate the issues involved by describing a pregnancy management case in which a treatment plan was modified based on a DTC result. A woman whose personal and family history were otherwise unremarkable for thromboembolism learned through DTC testing about the presence of a prothrombin (factor 2) gene mutation (rs1799963). Twice daily injections of enoxaparin were recommended throughout pregnancy for this patient who, without prior knowledge of this mutation, would not have been offered such therapy. Moreover, genetically based medical guidelines are a moving target, and treatment of thrombophilic conditions in asymptomatic patients is controversial. We address the state of the art in actionable personalized medicine with respect to clotting disorders in pregnancy, as well as other factors at play— economics, patient preference, and clinical decision support. We also discuss what steps are needed to increase the utility of genomic data in personalized medicine by collecting information and converting it into actionable knowledge. Journal of Personalized Medicine 2012-10-30 2 4 Article 10.3390/jpm2040192 192 200 2075-4426 2012-10-30 doi: 10.3390/jpm2040192 Jessica Tenenbaum Andra James Kristin Paulyson-Nuñez http://www.mdpi.com/2075-4426/2/4/175 CYP3A ranks among the most abundant cytochrome P450 enzymes in the liver, playing a dominant role in metabolic elimination of clinically used drugs. A main member in CYP3A family, CYP3A4 expression and activity vary considerably among individuals, attributable to genetic and non-genetic factors, affecting drug dosage and efficacy. However, the extent of genetic influence has remained unclear. This review assesses current knowledge on the genetic factors influencing CYP3A4 activity. Coding region CYP3A4 polymorphisms are rare and account for only a small portion of inter-person variability in CYP3A metabolism. Except for the promoter allele CYP3A4*1B with ambiguous effect on expression, common CYP3A4 regulatory polymorphisms were thought to be lacking. Recent studies have identified a relatively common regulatory polymorphism, designated CYP3A4*22 with robust effects on hepatic CYP3A4 expression. Combining CYP3A4*22 with CYP3A5 alleles *1, *3 and *7 has promise as a biomarker predicting overall CYP3A activity. Also contributing to variable expression, the role of polymorphisms in transcription factors and microRNAs is discussed. Journal of Personalized Medicine 2012-10-29 2 4 Review 10.3390/jpm2040175 175 191 2075-4426 2012-10-29 doi: 10.3390/jpm2040175 Danxin Wang Wolfgang Sadee http://www.mdpi.com/2075-4426/2/4/158 HMG-CoA reductase inhibitors, commonly known as statins, are some of the most widely prescribed medications worldwide and have been shown to be effective at lowering cholesterol in numerous long-term prospective trials, yet there are significant limitations to their use. First, patients receiving statin therapy have relatively low levels of medication adherence compared with other drug classes. Next, numerous statin formulations are available, each with its own unique safety and efficacy profile, and it may be unclear to prescribers which treatment is optimal for their patients. Finally, statins have class-wide side effects of myopathy and rhabdomyolysis that have resulted in a product recall and dosage limitations. Recent evidence suggests that two genomic markers, KIF6 and SLCO1B1, may inform the therapy choice of patients initiating statins. Given the prevalence of statin usage, their potential health advantages and their overall cost to the healthcare system, there could be significant clinical benefit from creating personalized treatment regimens. Ultimately, if this approach is effective it may encourage higher adoption of generic statins when appropriate, promote adherence, lower rates of myopathy, and overall achieve higher value cardiovascular care. This paper will review the evidence for personalized prescribing of statins via KIF6 and SLCO1B1 and consider some of the implications for testing these markers as part of routine clinical care. Journal of Personalized Medicine 2012-10-17 2 4 Article 10.3390/jpm2040158 158 174 2075-4426 2012-10-17 doi: 10.3390/jpm2040158 William J. Canestaro David G. Brooks Donald Chaplin Niteesh K. Choudhry Elizabeth Lawler Lori Martell Troyen Brennan E. Robert Wassman http://www.mdpi.com/2075-4426/2/4/149 Thousands of samples for pharmacogenetic tests have been analysed in our laboratory since its establishment. In this article we describe some of the most interesting cases of CYP poor metabolisers associated with adverse reactions to psychotropic drugs. Prevention of disease/illness, including Adverse Drug Reaction (ADR), is an aim of modern medicine. Scientific data supports the fact that evaluation of drug toxicology includes several factors, one of which is genetic variations in pharmacodynamics and pharmacokinetics of drug pathways. These variations are only a part of toxicity evaluation, however, even if it would help to prevent only a small percentage of patients from suffering adverse drug reactions, especially life threatening ADRs, pharmacogenetic testing should play a significant role in any modern psychopharmacologic practice. Medical practitioners should also consider the use of other medications or alternative dosing strategies for drugs in patients identified as altered metabolisers. This will promise not only better and safer treatments for patients, but also potentially lowering overall healthcare costs. Journal of Personalized Medicine 2012-10-01 2 4 Case Report 10.3390/jpm2040149 149 157 2075-4426 2012-10-01 doi: 10.3390/jpm2040149 Irina Piatkov Trudi Jones Mark McLean http://www.mdpi.com/2075-4426/2/4/138 We hypothesize that local customized modeling will provide more accurate mortality prediction than the current standard approach using existing scoring systems. Mortality prediction models were developed for two subsets of patients in Multi-parameter Intelligent Monitoring for Intensive Care (MIMIC), a public de-identified ICU database, and for the subset of patients >80 years old in a cardiac surgical patient registry. Logistic regression (LR), Bayesian network (BN) and artificial neural network (ANN) were employed. The best-fitted models were tested on the remaining unseen data and compared to either the Simplified Acute Physiology Score (SAPS) for the ICU patients, or the EuroSCORE for the cardiac surgery patients. Local customized mortality prediction models performed better as compared to the corresponding current standard severity scoring system for all three subsets of patients: patients with acute kidney injury (AUC = 0.875 for ANN, vs. SAPS, AUC = 0.642), patients with subarachnoid hemorrhage (AUC = 0.958 for BN, vs. SAPS, AUC = 0.84), and elderly patients undergoing open heart surgery (AUC = 0.94 for ANN, vs. EuroSCORE, AUC = 0.648). Rather than developing models with good external validity by including a heterogeneous patient population, an alternative approach would be to build models for specific patient subsets using one’s local database. Journal of Personalized Medicine 2012-09-27 2 4 Article 10.3390/jpm2040138 138 148 2075-4426 2012-09-27 doi: 10.3390/jpm2040138 Leo Anthony Celi Sean Galvin Guido Davidzon Joon Lee Daniel Scott Roger Mark http://www.mdpi.com/2075-4426/2/3/119 Sports-related genetic testing is a sector of the diverse direct-to-consumer (DTC) industry that has not yet been examined thoroughly by academic scholars. A systematic search was used to identify companies in this sector and content analysis of online information was performed. More than a dozen companies were identified. Marketing practices observed generally did not target parents for child testing, and marketing images were mild compared to images used in popular media. Information was provided at a high reading level (industry-wide Flesh-Kincaid Grade Levels > 11). While ~75% of companies provide privacy policies and terms of service prior to purchase and ~40% provide scientific citations for their tests. Journal of Personalized Medicine 2012-09-12 2 3 Article 10.3390/jpm2030119 119 137 2075-4426 2012-09-12 doi: 10.3390/jpm2030119 Jennifer K. Wagner Charmaine D. Royal http://www.mdpi.com/2075-4426/2/3/93 The concepts of health and health care are moving towards the notion of personalized preventive health maintenance and away from an exclusive focus on the cure of disease. This is against the backdrop of contemporary public health challenges that include increasing costs, worsening outcomes, ‘diabesity’ epidemics, and anticipated physician shortages. Personalized preventive medicine could be critical to solving public health challenges at their causal root. This paper sets forth a vision and plan for the realization of preventive medicine by 2050 and examines efforts already underway such as participatory health initiatives, the era of big health data, and qualitative shifts in mindset. Journal of Personalized Medicine 2012-09-12 2 3 Opinion 10.3390/jpm2030093 93 118 2075-4426 2012-09-12 doi: 10.3390/jpm2030093 Melanie Swan http://www.mdpi.com/2075-4426/2/3/77 The traditional approach to the treatment of advanced non-small cell lung cancer (NSCLC) relied on the uniform use of cytotoxic chemotherapy. Over the last eight years, this paradigm of care has been shifting towards the use of molecularly targeted agents. Epidermal growth factor receptor (EGFR) mutations have emerged as an important biomarker for these targeted agents and multiple studies have shown that tyrosine kinase inhibitors (TKI) that inhibit EGFR are superior to traditional chemotherapy in patients possessing an EGFR mutation. Nationally funded health care systems face a number of challenges in implementing these targeted therapies, most related to the need to test for biomarkers that predict likelihood of benefiting from the drug. These obstacles include the challenge of getting a large enough tissue sample, workload of involved specialists, reliability of subtyping in NSCLC, differences in biomarker tests, and the disconnect between the funding of drugs and the related biomarker test. In order to improve patient outcomes, in a national healthcare system, there is a need for governments to accept the changing paradigm, invest in technology and build capacity for molecular testing to facilitate the implementation of improved patient care. Journal of Personalized Medicine 2012-09-10 2 3 Review 10.3390/jpm2030077 77 92 2075-4426 2012-09-10 doi: 10.3390/jpm2030077 David E. Dawe Peter M. Ellis http://www.mdpi.com/2075-4426/2/3/71 Breast cancer is the most common malignancy among women in the United States with the second highest incidence of cancer-related death following lung cancer. The decision-making process regarding adjuvant therapy is a time intensive dialogue between the patient and her oncologist. There are multiple tools that help individualize the treatment options for a patient. Population-based analysis with Adjuvant! Online and genomic profiling with Oncotype DX are two commonly used tools in patients with early stage, node-negative breast cancer. This case report illustrates a situation in which the population-based prognostic and predictive information differed dramatically from that obtained from genomic profiling and affected the patient’s decision. In light of this case, we discuss the benefits and limitations of these tools. Journal of Personalized Medicine 2012-09-10 2 3 Case Report 10.3390/jpm2030071 71 76 2075-4426 2012-09-10 doi: 10.3390/jpm2030071 Steven R. Schuster Barbara A. Pockaj Mary R. Bothe Paru S. David Donald W. Northfelt http://www.mdpi.com/2075-4426/2/2/50 Infectious disease management essentially consists in identifying the microbial cause(s) of an infection, initiating if necessary antimicrobial therapy against microbes, and controlling host reactions to infection. In clinical microbiology, the turnaround time of the diagnostic cycle (>24 hours) often leads to unnecessary suffering and deaths; approaches to relieve this burden include rapid diagnostic procedures and more efficient transmission or interpretation of molecular microbiology results. Although rapid nucleic acid-based diagnostic testing has demonstrated that it can impact on the transmission of hospital-acquired infections, we believe that such life-saving procedures should be performed closer to the patient, in dedicated 24/7 laboratories of healthcare institutions, or ideally at point of care. While personalized medicine generally aims at interrogating the genomic information of a patient, drug metabolism polymorphisms, for example, to guide drug choice and dosage, personalized medicine concepts are applicable in infectious diseases for the (rapid) identification of a disease-causing microbe and determination of its antimicrobial resistance profile, to guide an appropriate antimicrobial treatment for the proper management of the patient. The implementation of point-of-care testing for infectious diseases will require acceptance by medical authorities, new technological and communication platforms, as well as reimbursement practices such that time- and life-saving procedures become available to the largest number of patients. Journal of Personalized Medicine 2012-05-02 2 2 Review 10.3390/jpm2020050 50 70 2075-4426 2012-05-02 doi: 10.3390/jpm2020050 Luc Bissonnette Michel G. Bergeron http://www.mdpi.com/2075-4426/2/2/35 The incorporation of individualized molecular therapeutics into routine clinical practice for both non-small cell lung cancer (NSCLC) and melanoma are amongst the most significant advances of the last decades in medical oncology. In NSCLC activating somatic mutations in exons encoding the tyrosine kinase domain of the Epidermal Growth Factor Receptor (EGFR) gene have been found to be predictive of a response to treatment with tyrosine kinase inhibitors (TKI), erlotinib or gefitinib. More recently the EML4-ALK fusion gene which occurs in 3–5% of NSCLC has been found to predict sensitivity to crizotinib an inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Similarly in melanoma, 50% of cases have BRAF mutations in exon 15 mostly V600E and these cases are sensitive to the BRAF inhibitors vemurafenib or dabrafenib. In a Phase III study of advanced melanoma cases with this mutation vemurafenib improved survival from 64% to 84% at 6 months, when compared with dacarbazine. In both NSCLC and melanoma clinical benefit is not obtained in patients without these genomic changes, and moreover in the case of vemurafenib the therapy may theoretically induce proliferation of cases of melanoma without BRAF mutations. An emerging clinical challenge is that of acquired resistance after initial responses to targeted therapeutics. Resistance to the TKI’s in NSCLC is most frequently due to acquisition of secondary mutations within the tyrosine kinase of the EGFR or alternatively activation of alternative tyrosine kinases such as C-MET. Mechanisms of drug resistance in melanoma to vemurafenib do not involve mutations in BRAF itself but are associated with a variety of molecular changes including RAF1 or COT gene over expression, activating mutations in RAS or increased activation of the receptor tyrosine kinase PDGFRβ. Importantly these data support introducing re-biopsy of tumors at progression to continue to personalize the choice of therapy throughout the patient’s disease course. Journal of Personalized Medicine 2012-04-10 2 2 Review 10.3390/jpm2020035 35 49 2075-4426 2012-04-10 doi: 10.3390/jpm2020035 Fergal C. Kelleher Benjamin Solomon Grant A. McArthur http://www.mdpi.com/2075-4426/2/1/15 Oncology is one of the most important fields of personalized medicine as a majority of efforts in this field have recently centered on targeted cancer drug development. New tools are continuously being developed that promise to make cancer treatment more efficacious while causing fewer side effects. Like most industries, the biopharmaceutical industry is also following certain global trends and these are analyzed in this article. As academia and industry are mutually dependent on each other, researchers in the field should be aware of those trends and the immediate consequences for their research. It is important for the future of this field that there is a healthy relationship among all interested parties as the challenges of personalized medicine are becoming ever more complex. Journal of Personalized Medicine 2012-03-07 2 1 Opinion 10.3390/jpm2010015 15 34 2075-4426 2012-03-07 doi: 10.3390/jpm2010015 Roman Fleck Daniel Bach http://www.mdpi.com/2075-4426/2/1/1 Cancer is one of the leading causes of death in the United States, and more than 1.5 million new cases and more than 0.5 million deaths were reported during 2010 in the United States alone. Following completion of the sequencing of the human genome, substantial progress has been made in characterizing the human epigenome, proteome, and metabolome; a better understanding of pharmacogenomics has been developed, and the potential for customizing health care for the individual has grown tremendously. Recently, personalized medicine has mainly involved the systematic use of genetic or other information about an individual patient to select or optimize that patient’s preventative and therapeutic care. Molecular profiling in healthy and cancer patient samples may allow for a greater degree of personalized medicine than is currently available. Information about a patient’s proteinaceous, genetic, and metabolic profile could be used to tailor medical care to that individual’s needs. A key attribute of this medical model is the development of companion diagnostics, whereby molecular assays that measure levels of proteins, genes, or specific mutations are used to provide a specific therapy for an individual’s condition by stratifying disease status, selecting the proper medication, and tailoring dosages to that patient’s specific needs. Additionally, such methods can be used to assess a patient’s risk factors for a number of conditions and to tailor individual preventative treatments. Recent advances, challenges, and future perspectives of personalized medicine in cancer are discussed. Journal of Personalized Medicine 2012-01-30 2 1 Review 10.3390/jpm2010001 1 14 2075-4426 2012-01-30 doi: 10.3390/jpm2010001 Mukesh Verma http://www.mdpi.com/2075-4426/1/1/5 Nowadays the adjustment of medication for each patient is at the center of health strategy. Children can be considered as specific targets with their own specificities. In the oral route field some examples of drugs especially adapted to children can be found. Design is introduced in drug formulation to offer a better choice of products and now, children can be considered as partners in their own treatment. Enhanced comprehension of children's requirements can also lead to creation of drugs that improve compliance. Journal of Personalized Medicine 2011-12-06 1 1 Communication 10.3390/jpm1010005 5 16 2075-4426 2011-12-06 doi: 10.3390/jpm1010005 Pascale Gauthier Jean-Michel Cardot http://www.mdpi.com/2075-4426/1/1/1 A new vision of personalized medicine or personalized healthcare has evolved as a consequence of remarkable recent advances in technologies that allow to look at individual variation across the entire human genome and to identify personal risk factors behind many diseases and responses to therapy. These advances have greatly increased our understanding of how interactions between the entire genome and nongenomic factors result in health and disease and in therapeutic response. The challenge is now to translate this knowledge into benefits for the individual patient. I expect the Journal of Personalized Medicine to become the premier venue for the rapid and freely accessible publication of high quality manuscripts dealing with this vision for scientists around the world. Journal of Personalized Medicine 2011-03-28 1 1 Editorial 10.3390/jpm1010001 1 4 2075-4426 2011-03-28 doi: 10.3390/jpm1010001 Urs A. Meyer