Open AccessReview
Development of the Precision Link Biobank at Boston Children’s Hospital: Challenges and Opportunities
J. Pers. Med. 2017, 7(4), 21; doi:10.3390/jpm7040021 -
Abstract
Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from
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Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from electronic health records (EHR). The Biobank was launched after multiple stakeholders’ input and implemented initially in a pilot phase before hospital-wide expansion in 2016. In-person informed consent is obtained from all participants enrolling in the Biobank and provides permission to: (1) access EHR data for research; (2) collect and use residual specimens produced as by-products of routine care; and (3) share de-identified data and specimens outside of the institution. Participants are recruited throughout the hospital, across diverse clinical settings. We have enrolled 4900 patients to date, and 41% of these have an associated blood sample for DNA processing. Current efforts are focused on aligning the Biobank with other ongoing research efforts at our institution and extending our electronic consenting system to support remote enrollment. A number of pediatric-specific challenges and opportunities is reviewed, including the need to re-consent patients when they reach 18 years of age, the ability to enroll family members accompanying patients and alignment with disease-specific research efforts at our institution and other pediatric centers to increase cohort sizes, particularly for rare diseases. Full article
Open AccessFeature PaperReview
Pharmacogenomics Guided-Personalization of Warfarin and Tamoxifen
J. Pers. Med. 2017, 7(4), 20; doi:10.3390/jpm7040020 -
Abstract
The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date
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The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxifen therapy. Further, highlighting the clinical experiences that we have gained over the past ten years of running a personalized medicine program, we will offer our perspectives on the utility and the limitations of pharmacogenomics-guided care for warfarin and tamoxifen therapy. Full article
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Open AccessArticle
Fixed and Adaptive Parallel Subgroup-Specific Design for Survival Outcomes: Power and Sample Size
J. Pers. Med. 2017, 7(4), 19; doi:10.3390/jpm7040019 -
Abstract
Biomarker-guided clinical trial designs, which focus on testing the effectiveness of a biomarker-guided approach to treatment in improving patient health, have drawn considerable attention in the era of stratified medicine with many different designs being proposed in the literature. However, planning such trials
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Biomarker-guided clinical trial designs, which focus on testing the effectiveness of a biomarker-guided approach to treatment in improving patient health, have drawn considerable attention in the era of stratified medicine with many different designs being proposed in the literature. However, planning such trials to ensure they have sufficient power to test the relevant hypotheses can be challenging and the literature often lacks guidance in this regard. In this study, we focus on the parallel subgroup-specific design, which allows the evaluation of separate treatment effects in the biomarker-positive subgroup and biomarker-negative subgroup simultaneously. We also explore an adaptive version of the design, where an interim analysis is undertaken based on a fixed percentage of target events, with the option to stop each biomarker-defined subgroup early for futility or efficacy. We calculate the number of events and patients required to ensure sufficient power in each of the biomarker-defined subgroups under different scenarios when the primary outcome is time-to-event. For the adaptive version, stopping probabilities are also explored. Since multiple hypotheses are being tested simultaneously, and multiple interim analyses are undertaken, we also focus on controlling the overall type I error rate by way of multiplicity adjustment. Full article
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Open AccessFeature PaperReview
Variation in CYP2A6 Activity and Personalized Medicine
J. Pers. Med. 2017, 7(4), 18; doi:10.3390/jpm7040018 -
Abstract
The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant substrates, including nicotine—the primary psychoactive component in cigarette smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting in extensive interindividual variation in CYP2A6 enzyme activity and the rate of metabolism
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The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant substrates, including nicotine—the primary psychoactive component in cigarette smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting in extensive interindividual variation in CYP2A6 enzyme activity and the rate of metabolism of nicotine and other CYP2A6 substrates including cotinine, tegafur, letrozole, efavirenz, valproic acid, pilocarpine, artemisinin, artesunate, SM-12502, caffeine, and tyrosol. CYP2A6 expression and activity are also impacted by non-genetic factors, including induction or inhibition by pharmacological, endogenous, and dietary substances, as well as age-related changes, or interactions with other hepatic enzymes, co-enzymes, and co-factors. As variation in CYP2A6 activity is associated with smoking behavior, smoking cessation, tobacco-related lung cancer risk, and with altered metabolism and resulting clinical responses for several therapeutics, CYP2A6 expression and enzyme activity is an important clinical consideration. This review will discuss sources of variation in CYP2A6 enzyme activity, with a focus on the impact of CYP2A6 genetic variation on metabolism of the CYP2A6 substrates. Full article
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Open AccessArticle
Access to Guideline-Recommended Pharmacogenomic Tests for Cancer Treatments: Experience of Providers and Patients
J. Pers. Med. 2017, 7(4), 17; doi:10.3390/jpm7040017 -
Abstract
Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers’ and patients’ experiences and views on test access
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Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers’ and patients’ experiences and views on test access as well as strategies used for gaining access. We interviewed clinicians who prescribed medications that should be guided by pharmacogenomic testing and patients who received those prescriptions. We organized the themes into the four dimensions suggested by the World Health Organization framework on access to medications and health technologies. Guideline-recommended pharmacogenomic tests for cancer care are generally available, although the timeliness of return of test results is sometimes suboptimal. Accessibility of pharmacogenomic tests is made challenging by the process of ordering pharmacogenomic tests, which is time-consuming. Affordability is a barrier to some patients as expressed by both providers and patients, who noted that the cost of pharmacogenomic tests and medications is high. Acceptability of the tests is high as both providers and patients view the tests positively. Understanding challenges to accessing pharmacogenomic tests will allow policymakers to develop policies that streamline access to genomics-based technologies to improve population health. Full article
Open AccessArticle
Psychiatric Disorders Differently Correlate with Physical Self-Rated Health across Ethnic Groups
J. Pers. Med. 2017, 7(4), 6; doi:10.3390/jpm7040006 -
Abstract
In this study, we compared 10 ethnic groups for associations between psychiatric disorders and physical self-rated health (SRH) in the United States. Data came from the Collaborative Psychiatric Epidemiology Surveys (CPES), 2001–2003. The study included 7587 non-Latino White, 4746 African American, 1442 Mexican,
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In this study, we compared 10 ethnic groups for associations between psychiatric disorders and physical self-rated health (SRH) in the United States. Data came from the Collaborative Psychiatric Epidemiology Surveys (CPES), 2001–2003. The study included 7587 non-Latino White, 4746 African American, 1442 Mexican, 1106 other Hispanic, 656 other Asian, 600 Chinese, 577 Cuban, 520 Vietnamese, 508 Filipino, and 495 Puerto Rican individuals. The Composite International Diagnostic Interview (CIDI) was used to measure psychiatric disorders, including major depressive disorder (MDD), general anxiety disorder (GAD), social phobia, panic disorder, post-traumatic stress disorder (PTSD), alcohol abuse, and binge eating disorders. A single-item measure was used to estimate physical SRH. Demographic (age and gender) and socioeconomic (education and income) factors were also measured. Unadjusted and adjusted correlations between psychiatric disorders and physical SRH were calculated. Major ethnic variations were found in the correlation between psychiatric disorders and physical SRH; as well as the role of demographic and socioeconomic status (SES) factors in explaining these associations. non-Hispanic Whites, Cubans, and African Americans showed more correlations between psychiatric disorders and physical SRH than other ethnic groups. In non-Hispanic Whites, the associations between psychiatric disorders and physical SRH were explained by demographic factors. In African Americans, the link between psychiatric disorders and poor physical SRH were explained by SES indicators. In conclusion, although single-item physical SRH measures are traditionally assumed to reflect the physical health needs of populations, they may also indicate psychiatric disorders in some ethnic groups, such as non-Hispanic Whites, Cubans, and African Americans. Demographic and socioeconomic factors also have differential roles in explaining the link between psychiatric disorders and physical SRH. Physical SRH does not exclusively reflect physical health, and it may be more biased by mental health across some ethnic groups. Full article
Open AccessArticle
Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms
J. Pers. Med. 2017, 7(4), 16; doi:10.3390/jpm7040016 -
Abstract
Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable
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Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern. Full article
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Open AccessArticle
Polymorphisms in FFAR4 (GPR120) Gene Modulate Insulin Levels and Sensitivity after Fish Oil Supplementation
J. Pers. Med. 2017, 7(4), 15; doi:10.3390/jpm7040015 -
Abstract
The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9–2.2 g of eicosapentaenoic acid
[...] Read more.
The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9–2.2 g of eicosapentaenoic acid (EPA) and 1.1 g of docosahexaenoic acid (DHA)) during six weeks. Biochemical parameters were taken before and after the supplementation. Using the HapMap database and the tagger procedure in Haploview, 12 tagging SNPs in FFAR4 were selected and then genotyped using TaqMan technology. Transcript expression levels were measured for 30 participants in peripheral mononuclear blood cells. DNA methylation levels were measured for 35 participants in leukocytes. In silico analyses were also performed. Four gene–diet interactions on fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) index values were found. rs17108973 explained a significant proportion of the variance of insulin levels (3.0%) and HOMA-IR (2.03%) index values. Splice site prediction was different depending on the allele for rs11187527. rs17108973 and rs17484310 had different affinity for transcription factors depending on the allele. n-3 FAs effectively improve insulin-related traits for major allele homozygotes of four FFAR4 SNPs as opposed to carriers of the minor alleles. Full article
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Open AccessFeature PaperArticle
Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
J. Pers. Med. 2017, 7(4), 14; doi:10.3390/jpm7040014 -
Abstract
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In
[...] Read more.
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug–CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs. Subsequently, we performed a focused literature review for drugs commonly used in pediatrics, defined as more than 5000 pediatric patients exposed in the decade-long EHR cohort. There were 48 drug–CYP interactions with a high level of evidence in the CPIC database. Of those, only 10 drugs were commonly used in children (ondansetron, oxycodone, codeine, omeprazole, lansoprazole, sertraline, amitriptyline, citalopram, escitalopram, and risperidone). For these drugs, reports of the drug–CYP interaction in cohorts including children were sparse. There are adequate data for implementation of genotype-guided therapy for children for three of the 10 commonly used drugs (codeine, omeprazole and lansoprazole). For the majority of commonly used drugs with known CYP interactions, more data are required to support pharmacogenomic implementation in children. Full article
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Open AccessCommentary
Personomics: The Missing Link in the Evolution from Precision Medicine to Personalized Medicine
J. Pers. Med. 2017, 7(4), 11; doi:10.3390/jpm7040011 -
Abstract
Clinical practice guidelines have been developed for many common conditions based on data from randomized controlled trials. When medicine is informed solely by clinical practice guidelines, however, the patient is not treated as an individual, but rather a member of a group. Precision
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Clinical practice guidelines have been developed for many common conditions based on data from randomized controlled trials. When medicine is informed solely by clinical practice guidelines, however, the patient is not treated as an individual, but rather a member of a group. Precision medicine, as defined herein, characterizes unique biological characteristics of the individual or of specimens obtained from an individual to tailor diagnostics and therapeutics to a specific patient. These unique biological characteristics are defined by the tools of precision medicine: genomics, proteomics, metabolomics, epigenomics, pharmacogenomics, and other “-omics.” Personalized medicine, as defined herein, uses additional information about the individual derived from knowing the patient as a person. These unique personal characteristics are defined by tools known as personomics which takes into account an individual’s personality, preferences, values, goals, health beliefs, social support network, financial resources, and unique life circumstances that affect how and when a given health condition will manifest in that person and how that condition will respond to treatment. In this paradigm, precision medicine may be considered a necessary step in the evolution of medical care to personalized medicine, with personomics as the missing link. Full article
Open AccessReview
Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy
J. Pers. Med. 2017, 7(4), 13; doi:10.3390/jpm7040013 -
Abstract
Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising
[...] Read more.
Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising strategies. This strategy aims to restore the reading frame, thus producing a truncated, yet functioning dystrophin protein. In 2016, the Food and Drug Administration (FDA) conditionally approved the first AO-based drug, eteplirsen (Exondys 51), developed for DMD exon 51 skipping. An accurate and reproducible method to quantify exon skipping efficacy is essential for evaluating the therapeutic potential of different AOs sequences. However, previous in vitro screening studies have been hampered by the limited proliferative capacity and insufficient amounts of dystrophin expressed by primary muscle cell lines that have been the main system used to evaluate AOs sequences. In this paper, we illustrate the challenges associated with primary muscle cell lines and describe a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies. Full article
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Open AccessReview
Personalized Nanomedicine: A Revolution at the Nanoscale
J. Pers. Med. 2017, 7(4), 12; doi:10.3390/jpm7040012 -
Abstract
Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near
[...] Read more.
Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near future due to its multiple advantages, namely its versatility to adapt a drug to a cohort of patients. In the present review, the properties and requirements of pharmaceutical dosage forms at the nanoscale, so-called nanomedicines, are been highlighted. An overview of the main current nanomedicines in pre-clinical and clinical development is presented, detailing the challenges to the personalization of these therapies. Next, the process of development of novel nanomedicines is described, from their design in research labs to their arrival on the market, including considerations for the design of nanomedicines adapted to the requirements of the market to achieve safe, effective, and quality products. Finally, attention is given to the point of view of the pharmaceutical industry, including regulation issues applied to the specific case of personalized medicine. The authors expect this review to be a useful overview of the current state of the art of nanomedicine research and industrial production, and the future opportunities of personalized medicine in the upcoming years. The authors encourage the development and marketing of novel personalized nanomedicines. Full article
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Open AccessReview
Value-Based Pricing and Reimbursement in Personalised Healthcare: Introduction to the Basic Health Economics
J. Pers. Med. 2017, 7(3), 10; doi:10.3390/jpm7030010 -
Abstract
‘Value-based’ outcomes, pricing, and reimbursement are widely discussed as health sector reforms these days. In this paper, we discuss their meaning and relationship in the context of personalized healthcare, defined as receipt of care conditional on the results of a biomarker-based diagnostic test.
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‘Value-based’ outcomes, pricing, and reimbursement are widely discussed as health sector reforms these days. In this paper, we discuss their meaning and relationship in the context of personalized healthcare, defined as receipt of care conditional on the results of a biomarker-based diagnostic test. We address the question: “What kinds of pricing and reimbursement models should be applied in personalized healthcare?” The simple answer is that competing innovators and technology adopters should have incentives that promote long-term dynamic efficiency. We argue that—to meet this social objective of optimal innovation in personalized healthcare—payers, as agents of their plan participants, should aim to send clear signals to their suppliers about what they value. We begin by revisiting the concept of value from an economic perspective, and argue that a broader concept of value is needed in the context of personalized healthcare. We discuss the market for personalized healthcare and the interplay between price and reimbursement. We close by emphasizing the potential barrier posed by inflexible or cost-based reimbursement systems, especially for biomarker-based predictive tests, and how these personalized technologies have global public goods characteristics that require global value-based differential pricing to achieve dynamic efficiency in terms of the optimal rate of innovation and adoption. Full article
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Open AccessCommentary
Personalized Computational Models as Biomarkers
J. Pers. Med. 2017, 7(3), 9; doi:10.3390/jpm7030009 -
Abstract
Biomarkers are cornerstones of clinical medicine, and personalized medicine, in particular, is highly dependent on reliable and highly accurate biomarkers for individualized diagnosis and treatment choice. Modern omics technologies, such as genome sequencing, allow molecular profiling of individual patients with unprecedented resolution, but
[...] Read more.
Biomarkers are cornerstones of clinical medicine, and personalized medicine, in particular, is highly dependent on reliable and highly accurate biomarkers for individualized diagnosis and treatment choice. Modern omics technologies, such as genome sequencing, allow molecular profiling of individual patients with unprecedented resolution, but biomarkers based on these technologies often lack the dynamic element to follow the progression of a disease or response to therapy. Here, we discuss computational models as a new conceptual approach to biomarker discovery and design. Being able to integrate a large amount of information, including dynamic information, computational models can simulate disease evolution and response to therapy with high sensitivity and specificity. By populating these models with personal data, they can be highly individualized and will provide a powerful new tool in the armory of personalized medicine. Full article
Open AccessArticle
Dairy Product Consumption Interacts with Glucokinase (GCK) Gene Polymorphisms Associated with Insulin Resistance
J. Pers. Med. 2017, 7(3), 8; doi:10.3390/jpm7030008 -
Abstract
Dairy product intake and a person’s genetic background have been reported to be associated with the risk of type 2 diabetes (T2D). The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis
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Dairy product intake and a person’s genetic background have been reported to be associated with the risk of type 2 diabetes (T2D). The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis parameters. A validated food frequency questionnaire, fasting blood samples, and glucokinase (GCK) genotypes were analyzed in 210 healthy participants. An interaction between rs1799884 in GCK and dairy intake on the homeostasis model assessment of insulin resistance was identified. Secondly, human hepatocellular carcinoma cells (HepG2) were grown in a high-glucose medium and incubated with either 1-dairy proteins: whey, caseins, and a mixture of whey and casein; and 2-four amino acids (AA) or mixtures of AA. The expression of GCK-related genes insulin receptor substrate-1 (IRS-1) and fatty acid synthase (FASN) was increased with whey protein isolate or hydrolysate. Individually, leucine increased IRS-1 expression, whereas isoleucine and valine decreased FASN expression. A branched-chain AA mixture decreased IRS-1 and FASN expression. In conclusion, carriers of the A allele for rs1799884 in the GCK gene may benefit from a higher intake of dairy products to maintain optimal insulin sensitivity. Moreover, the results show that whey proteins affect the expression of genes related to glucose metabolism. Full article
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Open AccessReview
Empowering Mayo Clinic Individualized Medicine with Genomic Data Warehousing
J. Pers. Med. 2017, 7(3), 7; doi:10.3390/jpm7030007 -
Abstract
Individualized medicine enables better diagnoses and treatment decisions for patients and promotes research in understanding the molecular underpinnings of disease. Linking individual patient’s genomic and molecular information with their clinical phenotypes is crucial to these efforts. To address this need, the Center for
[...] Read more.
Individualized medicine enables better diagnoses and treatment decisions for patients and promotes research in understanding the molecular underpinnings of disease. Linking individual patient’s genomic and molecular information with their clinical phenotypes is crucial to these efforts. To address this need, the Center for Individualized Medicine at Mayo Clinic has implemented a genomic data warehouse and a workflow management system to bring data from institutional electronic health records and genomic sequencing data from both clinical and research bioinformatics sources into the warehouse. The system is the foundation for Mayo Clinic to build a suite of tools and interfaces to support various clinical and research use cases. The genomic data warehouse is positioned to play a key role in enhancing the research capabilities and advancing individualized patient care at Mayo Clinic. Full article
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Open AccessArticle
The Clinical and Economic Impact of Inaccurate EGFR Mutation Tests in the Treatment of Metastatic Non-Small Cell Lung Cancer
J. Pers. Med. 2017, 7(3), 5; doi:10.3390/jpm7030005 -
Abstract
Advances in personalized medicine are supported by companion diagnostic molecular tests. Testing accuracy is critical for selecting patients for optimal therapy and reducing treatment-related toxicity. We assessed the clinical and economic impact of inaccurate test results between laboratory developed tests (LDTs) and a
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Advances in personalized medicine are supported by companion diagnostic molecular tests. Testing accuracy is critical for selecting patients for optimal therapy and reducing treatment-related toxicity. We assessed the clinical and economic impact of inaccurate test results between laboratory developed tests (LDTs) and a US Food and Drug Administration (FDA)-approved test for detection of epidermal growth factor receptor (EGFR) mutations. Using a hypothetical US cohort of newly diagnosed metastatic non-small cell lung cancer (NSCLC) patients and EURTAC (erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) clinical trial data, we developed a decision analytic model to estimate the probability of misclassification with LDTs compared to a FDA-approved test. We estimated the clinical and economic impact of inaccurate test results by quantifying progression-free and quality-adjusted progression-free life years (PFLYs, QAPFLYs) lost, and costs due to incorrect treatment. The base-case analysis estimated 2.3% (n = 1422) of 60,502 newly diagnosed metastatic NSCLC patients would be misclassified with LDTs compared to 1% (n = 577) with a FDA-approved test. An average of 477 and 194 PFLYs were lost among the misclassified patients tested with LDTs compared to the FDA-approved test, respectively. Aggregate treatment costs for patients tested with LDTs were approximately $7.3 million more than with the FDA-approved test, due to higher drug and adverse event costs among patients incorrectly treated with targeted therapy or chemotherapy, respectively. Invalid tests contributed to greater probability of patient misclassification and incorrect therapy. In conclusion, risks associated with inaccurate EGFR mutation tests pose marked clinical and economic consequences to society. Utilization of molecular diagnostic tests with demonstrated accuracy could help to maximize the potential of personalized medicine. Full article
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Open AccessArticle
Development and Initial Assessment of a Patient Education Video about Pharmacogenetics
J. Pers. Med. 2017, 7(2), 4; doi:10.3390/jpm7020004 -
Abstract
As few patient-friendly resources about pharmacogenetics are currently available, we aimed to create and assess a patient educational video on pharmacogenetic testing. A primary literature and resources review was conducted to inform the content and the format of the video. The educational video
[...] Read more.
As few patient-friendly resources about pharmacogenetics are currently available, we aimed to create and assess a patient educational video on pharmacogenetic testing. A primary literature and resources review was conducted to inform the content and the format of the video. The educational video was then created using a commercially available animation program and pilot tested in focus groups of the general public and by an online survey of pharmacists. Emerging themes from the focus groups and survey indicate a desire for appropriate risk contextualization and specific examples when pharmacogenetic testing may be beneficial. Focus group participants also expressed a preference for a video with live action, and more text to reinforce concepts. Pharmacists generally felt that the video was understandable for patients and relevant for decision-making regarding testing. Using this initial feedback and the identification of important concepts to include in pharmacogenetics educational tools, we plan to revise the video, perform additional evaluations, and publish the video for public use in the future. Full article
Open AccessArticle
Accuracy in Wrist-Worn, Sensor-Based Measurements of Heart Rate and Energy Expenditure in a Diverse Cohort
J. Pers. Med. 2017, 7(2), 3; doi:10.3390/jpm7020003 -
Abstract
The ability to measure physical activity through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. The aim of this work is to assess the accuracy of seven commercially available wrist-worn devices in estimating heart
[...] Read more.
The ability to measure physical activity through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. The aim of this work is to assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework. We evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 ± 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination. Devices reported the lowest error for cycling and the highest for walking. Device error was higher for males, greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest. In conclusion, most wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/). Full article
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Open AccessReview
Methods for the In Vitro Characterization of Nanomedicines—Biological Component Interaction
J. Pers. Med. 2017, 7(1), 2; doi:10.3390/jpm7010002 -
Abstract
The design of colloidal nanosystems intended for biomedical applications, specifically in the field of personalized medicine, has increased notably in the last years. Consequently, a variety of characterization techniques devoted to studying nanomedicine interactions with proteins and cells have been developed, since a
[...] Read more.
The design of colloidal nanosystems intended for biomedical applications, specifically in the field of personalized medicine, has increased notably in the last years. Consequently, a variety of characterization techniques devoted to studying nanomedicine interactions with proteins and cells have been developed, since a deep characterization of nanosystems is required before starting preclinical and clinical studies. In this context, this review aims to summarize the main techniques used to assess the interaction of nanomedicines with biological systems, highlighting their advantages and disadvantages. Testing designed nanomaterials with these techniques is required in order to have more information about their behavior on a physiological environment. Moreover, techniques used to study the interaction of nanomedicines with proteins, such as albumin and fibrinogen, are summarized. These interactions are not desired, since they usually are the first signal to the body for the activation of the immune system, which leads to the clearance of the exogenous components. On the other hand, techniques for studying the cell toxicity of nanosystems are also summarized, since this information is required before starting preclinical steps. The translation of knowledge from novel designed nanosystems at a research laboratory scale to real human therapies is usually a limiting or even a final point due to the lack of systematic studies regarding these two aspects: nanoparticle interaction with biological components and nanoparticle cytotoxicity. In conclusion, this review will be a useful support for those scientists aiming to develop nanosystems for nanomedicine purposes. Full article
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