Research

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10 pages, 875 KiB

Open AccessArticle

The Potential Benefit of Expedited Development and Approval Programs in Precision Medicine

by Ariel Kantor and Susanne B. Haga

J. Pers. Med. 2021, 11(1), 45; https://doi.org/10.3390/jpm11010045 - 14 Jan 2021

Cited by 7 | Viewed by 3533

Background: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued [...] Read more.

Background: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued growth of precision medicine drugs and devices. To facilitate the development and approval process of drugs for serious unmet needs, four expedited approval programs have been developed in the US: priority review, accelerated approval, fast track, and breakthrough therapy programs. Methods: To determine if expedited approval programs are fulfilling the intended goals, we reviewed drug approvals by the US Food and Drug Administration (FDA) between 2011 and 2017 for new molecular entities (NMEs). Results: From 2011 through 2017, the FDA approved 250 NMEs, ranging from 27 approvals in 2013 to 46 in 2017. The NME approvals spanned 22 different disease classes; almost one-third of all NMEs were for oncology treatments. Conclusions: As these pathways are utilized more, additional legislative changes may be needed to re-align incentives to promote continued development of innovative drugs for serious unmet needs in a safe, efficacious, and affordable manner. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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10 pages, 282 KiB

Open AccessArticle

Definition of Personalized Medicine and Targeted Therapies: Does Medical Familiarity Matter?

by Valentyn Fournier, Thomas Prebet, Alexandra Dormal, Maïté Brunel, Robin Cremer and Loris Schiaratura

J. Pers. Med. 2021, 11(1), 26; https://doi.org/10.3390/jpm11010026 - 04 Jan 2021

Cited by 4 | Viewed by 2743

Abstract

Personalized medicine (PM) is increasingly becoming a topic of discussion in public health policies and media. However, there is no consensus among definitions of PM in the scientific literature and the terms used to designate it, with some definitions emphasizing patient-centered aspects and [...] Read more.

Personalized medicine (PM) is increasingly becoming a topic of discussion in public health policies and media. However, there is no consensus among definitions of PM in the scientific literature and the terms used to designate it, with some definitions emphasizing patient-centered aspects and others emphasizing biomedical aspects. Furthermore, terms used to refer to PM (e.g., “pharmacogenomics” or, more often, “targeted therapies”) are diverse and differently used. To our knowledge, no study has apprehended the differences of definition and attitudes toward personalized medicine and targeted therapies according to level of familiarity with the medical field. Our cohort included 349 French students from three different academic fields, which modulated their familiarity level with the medical field. They were asked to associate words either to “personalized medicine” or “target therapies”. Then, they were asked to give an emotional valence to their associations. Results showed that nonfamiliar students perceived PM as more positive than targeted therapies (TT), whereas familiar students showed no difference. Only familiar students defined PM and TT with technical aspects such as genetics or immunology. Further studies are needed in the field in order to determine which other factors could influence the definitions of PM and TT and determine how these definitions could have an impact in a clinical setting. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

21 pages, 3901 KiB

Open AccessArticle

Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients

by Adrián Montaño, Jesús Hernández-Sánchez, Maribel Forero-Castro, María Matorra-Miguel, Eva Lumbreras, Cristina Miguel, Sandra Santos, Valentina Ramírez-Maldonado, José Luís Fuster, Natalia de Las Heras, Alfonso García-de Coca, Magdalena Sierra, Julio Dávila, Ignacio de la Fuente, Carmen Olivier, Juan Olazabal, Joaquín Martínez, Nerea Vega-García, Teresa González, Jesús María Hernández-Rivas and Rocío Benito Show full author list Hide full author list

J. Pers. Med. 2020, 10(3), 137; https://doi.org/10.3390/jpm10030137 - 21 Sep 2020

Cited by 4 | Viewed by 4471

Abstract

Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as [...] Read more.

Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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14 pages, 381 KiB

Open AccessFeature PaperArticle

Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

by John A. Lynch, Richard R. Sharp, Sharon A. Aufox, Sarah T. Bland, Carrie Blout, Deborah J. Bowen, Adam H. Buchanan, Colin Halverson, Margaret Harr, Scott J. Hebbring, Nora Henrikson, Christin Hoell, Ingrid A. Holm, Gail Jarvik, Iftikhar J. Kullo, David C. Kochan, Eric B. Larson, Amanda Lazzeri, Kathleen A. Leppig, Jill Madden, Maddalena Marasa, Melanie F. Myers, Josh Peterson, Cynthia A. Prows, Alanna Kulchak Rahm, James Ralston, Hila Milo Rasouly, Aaron Scrol, Maureen E. Smith, Amy Sturm, Kelsey Stuttgen, Georgia Wiesner, Marc S. Williams, Julia Wynn and Janet L. Williams Show full author list Hide full author list

J. Pers. Med. 2020, 10(2), 38; https://doi.org/10.3390/jpm10020038 - 13 May 2020

Cited by 12 | Viewed by 5815

Abstract

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine [...] Read more.

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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12 pages, 1469 KiB

Open AccessArticle

Application of Machine Learning Technique to Distinguish Parkinson’s Disease Dementia and Alzheimer’s Dementia: Predictive Power of Parkinson’s Disease-Related Non-Motor Symptoms and Neuropsychological Profile

by Haewon Byeon

J. Pers. Med. 2020, 10(2), 31; https://doi.org/10.3390/jpm10020031 - 28 Apr 2020

Cited by 11 | Viewed by 4317

Abstract

In order to develop a predictive model that can distinguish Parkinson’s disease dementia (PDD) from other dementia types, such as Alzheimer’s dementia (AD), it is necessary to evaluate and identify the predictive accuracy of the cognitive profile while considering the non-motor symptoms, such [...] Read more.

In order to develop a predictive model that can distinguish Parkinson’s disease dementia (PDD) from other dementia types, such as Alzheimer’s dementia (AD), it is necessary to evaluate and identify the predictive accuracy of the cognitive profile while considering the non-motor symptoms, such as depression and rapid eye movement (REM) sleep behavior disorders. This study compared Parkinson’s disease (PD)’s non-motor symptoms and the diagnostic predictive power of cognitive profiles that distinguish AD and PD using machine learning. This study analyzed 118 patients with AD and 110 patients with PDD, and all subjects were 60 years or older. In order to develop the PDD prediction model, the dataset was divided into training data (70%) and test data (30%). The prediction accuracy of the model was calculated by the recognition rate. The results of this study show that Parkinson-related non-motor symptoms, such as REM sleep behavior disorders, and cognitive screening tests, such as Korean version of Montreal Cognitive Assessment, were highly accurate factors for predicting PDD. It is required to develop customized screening tests that can detect PDD in the early stage based on these results. Furthermore, it is believed that including biomarkers such as brain images or cerebrospinal fluid as input variables will be more useful for developing PDD prediction models in the future. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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Review

Jump to: Research

34 pages, 1450 KiB

Open AccessReview

Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring

by Vivian Garzón, Rosa-Helena Bustos and Daniel G. Pinacho

J. Pers. Med. 2020, 10(4), 147; https://doi.org/10.3390/jpm10040147 - 25 Sep 2020

Cited by 14 | Viewed by 9770

Abstract

Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited [...] Read more.

Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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8 pages, 362 KiB

Open AccessReview

Stickler Syndrome: A Review of Clinical Manifestations and the Genetics Evaluation

by Megan Boothe, Robert Morris and Nathaniel Robin

J. Pers. Med. 2020, 10(3), 105; https://doi.org/10.3390/jpm10030105 - 27 Aug 2020

Cited by 41 | Viewed by 10584

Abstract

Stickler Syndrome (SS) is a multisystem collagenopathy frequently encountered by ophthalmologists due to the high rate of ocular complications. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes for [...] Read more.

Stickler Syndrome (SS) is a multisystem collagenopathy frequently encountered by ophthalmologists due to the high rate of ocular complications. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes for these patients. Systemic findings are also common, with craniofacial, skeletal, and auditory systems often involved. SS is genotypically and phenotypically heterogenous, which can make recognizing and correctly diagnosing individuals difficult. Molecular genetic testing should be considered in all individuals with suspected SS, as diagnosis not only assists in treatment and management of the patient but may also help identify other at-risk family members. Here we review common clinical manifestation of SS and genetic tests frequently ordered as part of the SS evaluation. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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19 pages, 2143 KiB

Open AccessReview

Nursing Personnel in the Era of Personalized Healthcare in Clinical Practice

by Marios Spanakis, Athina E. Patelarou and Evridiki Patelarou

J. Pers. Med. 2020, 10(3), 56; https://doi.org/10.3390/jpm10030056 - 29 Jun 2020

Cited by 11 | Viewed by 6644

Abstract

Personalized, stratified, or precision medicine (PM) introduces a new era in healthcare that tries to identify and predict optimum treatment outcomes for a patient or a cohort. It also introduces new scientific terminologies regarding therapeutic approaches and the need of their adoption from [...] Read more.

Personalized, stratified, or precision medicine (PM) introduces a new era in healthcare that tries to identify and predict optimum treatment outcomes for a patient or a cohort. It also introduces new scientific terminologies regarding therapeutic approaches and the need of their adoption from healthcare providers. Till today, evidence-based practice (EBP) was focusing on population averages and their variances among cohorts for clinical values that are essential for optimizing healthcare outcome. It can be stated that EBP and PM are complementary approaches for a modern healthcare system. Healthcare providers through EBP often see the forest (population averages) but miss the trees (individual patients), whereas utilization of PM may not see the forest for the trees. Nursing personnel (NP) play an important role in modern healthcare since they are consulting, educating, and providing care to patients whose needs often needs to be individualized (personalized nursing care, PNC). Based on the clinical issues earlier addressed from clinical pharmacology, EBP, and now encompassed in PM, this review tries to describe the challenges that NP have to face in order to meet the requisites of the new era in healthcare. It presents the demands that should be met for upgrading the provided education and expertise of NP toward an updated role in a modern healthcare system. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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20 pages, 296 KiB

Open AccessReview

Wise Management of Ovarian Cancer: On the Cutting Edge

by Stergios Boussios, Christos Mikropoulos, Eleftherios Samartzis, Peeter Karihtala, Michele Moschetta, Matin Sheriff, Afroditi Karathanasi, Agne Sadauskaite, Elie Rassy and Nicholas Pavlidis

J. Pers. Med. 2020, 10(2), 41; https://doi.org/10.3390/jpm10020041 - 21 May 2020

Cited by 53 | Viewed by 7500

Abstract

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. [...] Read more.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

14 pages, 455 KiB

Open AccessReview

A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia

by Rachele M. Hendricks-Sturrup, Jodi Clark-LoCascio and Christine Y. Lu

J. Pers. Med. 2020, 10(2), 23; https://doi.org/10.3390/jpm10020023 - 14 Apr 2020

Cited by 10 | Viewed by 5348

Abstract

Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism that affects an estimated 1/250 persons in the United States and abroad. FH is hallmarked by high low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. This review summarizes [...] Read more.

Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism that affects an estimated 1/250 persons in the United States and abroad. FH is hallmarked by high low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. This review summarizes recent global evidence showing the utility of FH genetic testing across diverse populations. Clinical and other qualitative outcomes following FH genetic testing were improved FH diagnosis, treatment initiation or continued treatment, treatment modification, improved total or LDL cholesterol levels, education on lifestyle management, and genetic counseling. This summary of evidence should be considered by those seeking overall evidence and knowledge gaps on the utility of FH genetic testing from a global perspective and for certain ethnic and age populations. These findings can be used to inform insurance policies and coverage decisions for FH genetic testing, policy recommendations to reduce the clinical and public health burden of FH, clinical practice and guidelines to improve the management of FH populations, and ongoing research involving FH genetic testing. We conclude that further investigations are needed to examine: (1) non-clinical outcomes following FH genetic testing; (2) patient-reported outcomes following FH genetic testing to convey patient experiences, values, and goals; and (3) clinical outcomes following FH genetic testing in non-Caucasian and pediatric populations in the United States and abroad. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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17 pages, 740 KiB

Open AccessReview

Promotion of Healthy Nutrition and Physical Activity Lifestyles for Teenagers: A Systematic Literature Review of The Current Methodologies

by María Vanessa Villasana, Ivan Miguel Pires, Juliana Sá, Nuno M. Garcia, Eftim Zdravevski, Ivan Chorbev, Petre Lameski and Francisco Flórez-Revuelta

J. Pers. Med. 2020, 10(1), 12; https://doi.org/10.3390/jpm10010012 - 01 Mar 2020

Cited by 15 | Viewed by 6714

Abstract

Amid obesity problems in the young population and apparent trends of spending a significant amount of time in a stationary position, promoting healthy nutrition and physical activities to teenagers is becoming increasingly important. It can rely on different methodologies, including a paper diary [...] Read more.

Amid obesity problems in the young population and apparent trends of spending a significant amount of time in a stationary position, promoting healthy nutrition and physical activities to teenagers is becoming increasingly important. It can rely on different methodologies, including a paper diary and mobile applications. However, the widespread use of mobile applications by teenagers suggests that they could be a more suitable tool for this purpose. This paper reviews the methodologies for promoting physical activities to healthy teenagers explored in different studies, excluding the analysis of different diseases. We found only nine studies working with teenagers and mobile applications to promote active lifestyles, including the focus on nutrition and physical activity. Studies report using different techniques to captivate the teenagers, including questionnaires and gamification techniques. We identified the common features used in different studies, which are: paper diary, diet diary, exercise diary, notifications, diet plan, physical activity registration, gamification, smoking cessation, pictures, game, and SMS, among others. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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