Journal of Personalized Medicine

13 pages, 995 KiB

Open AccessArticle

Impacts of Sex Differences in Pulse Pressure among Patients with Chronic Kidney Disease

by Hiroshi Kataoka, Yukako Sawara, Keiko Kawachi, Shun Manabe, Toshio Mochizuki and Kosaku Nitta

J. Pers. Med. 2019, 9(4), 52; https://doi.org/10.3390/jpm9040052 - 9 Dec 2019

Cited by 8 | Viewed by 4956

Abstract

Introduction: Though disease-related differences between the sexes have increasingly attracted attention, the renal impact of pulse pressure (PP) in patients with chronic kidney disease (CKD) has never been investigated comprehensively in relation to differences associated with sex. We aimed to examine sex [...] Read more.

Introduction: Though disease-related differences between the sexes have increasingly attracted attention, the renal impact of pulse pressure (PP) in patients with chronic kidney disease (CKD) has never been investigated comprehensively in relation to differences associated with sex. We aimed to examine sex differences in PP as a related factor of CKD progression from the perspective of atherosclerosis. Methods: A total of 156 patients with CKD matched according to age and estimated glomerular filtration rate (eGFR) were separated into sex-based cohorts. Multivariate Cox proportional hazards analyses were performed to identify factors associated with renal outcomes. Kaplan–Meier analyses were performed to assess disease progression, which was defined as a ≥50% estimated glomerular filtration rate (eGFR) decline or end-stage renal disease. Results: The mean age of the study participants was 58.9 ± 13.1 years, and the median follow-up period was 114.0 months. A multivariate Cox regression analysis showed that PP was significantly associated with disease progression among the entire cohort (p = 0.007). In the sex-based sub-cohort analyses, PP was significantly associated with disease progression in men (p = 0.0004) but not in women. Among the entire cohort, PP was correlated positively with age (p = 0.03) and negatively with high-density lipoprotein-cholesterol (HDL-C) level (p = 0.003). PP was significantly correlated with visceral fat area (VFA) (p = 0.04) and hemoglobin level (p = 0.04) in men and with HDL-C level (p = 0.003) in women. Conclusion: A high PP is a significant related factor of CKD progression, especially in men, in whom it is significantly associated with greater VFA and lower hemoglobin level. Full article

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18 pages, 1632 KiB

Open AccessReview

Potential Impact of MicroRNA Gene Polymorphisms in the Pathogenesis of Diabetes and Atherosclerotic Cardiovascular Disease

by Imadeldin Elfaki, Rashid Mir, Mohammad Muzaffar Mir, Faisel M AbuDuhier, Abdullatif Taha Babakr and Jameel Barnawi

J. Pers. Med. 2019, 9(4), 51; https://doi.org/10.3390/jpm9040051 - 25 Nov 2019

Cited by 40 | Viewed by 7298

Abstract

MicroRNAs (miRNAs) are endogenous, small (18–23 nucleotides), non-coding RNA molecules. They regulate the posttranscriptional expression of their target genes. MiRNAs control vital physiological processes such as metabolism, development, differentiation, cell cycle and apoptosis. The control of the gene expression by miRNAs requires efficient [...] Read more.

MicroRNAs (miRNAs) are endogenous, small (18–23 nucleotides), non-coding RNA molecules. They regulate the posttranscriptional expression of their target genes. MiRNAs control vital physiological processes such as metabolism, development, differentiation, cell cycle and apoptosis. The control of the gene expression by miRNAs requires efficient binding between the miRNA and their target mRNAs. Genome-wide association studies (GWASs) have suggested the association of single-nucleotide polymorphisms (SNPs) with certain diseases in various populations. Gene polymorphisms of miRNA target sites have been implicated in diseases such as cancers, diabetes, cardiovascular and Parkinson’s disease. Likewise, gene polymorphisms of miRNAs have been reported to be associated with diseases. In this review, we discuss the SNPs in miRNA genes that have been associated with diabetes and atherosclerotic cardiovascular disease in different populations. We also discuss briefly the potential underlining mechanisms through which these SNPs increase the risk of developing these diseases. Full article

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13 pages, 1146 KiB

Open AccessArticle

Feasibility of a mHealth Approach to Nutrition Counseling in an Appalachian State

by Melissa D. Olfert, Makenzie L. Barr, Rebecca L. Hagedorn, Dustin M. Long, Treah S. Haggerty, Mathew Weimer, Joseph Golden, Mary Ann Maurer, Jill D. Cochran, Tracy Hendershot, Stacey L. Whanger, Jay D. Mason and Sally L. Hodder

J. Pers. Med. 2019, 9(4), 50; https://doi.org/10.3390/jpm9040050 - 20 Nov 2019

Cited by 6 | Viewed by 5915

Abstract

West Virginia is a rural state with an aging population that may experience barriers to accessing nutritional and lifestyle counseling. This study examined feasibility of an online personalized nutrition tracking application, Good Measures (GM), with patients at seven health care clinics throughout the [...] Read more.

West Virginia is a rural state with an aging population that may experience barriers to accessing nutritional and lifestyle counseling. This study examined feasibility of an online personalized nutrition tracking application, Good Measures (GM), with patients at seven health care clinics throughout the state. Fourteen healthcare providers and 64 patients 18 years or older with a Body Mass Index (BMI) greater than or equal to 30 and access to the Internet were recruited for this 12-week feasibility study. Patient participants logged meals and exercise into the GM application via smart phone, tablet, or computer and virtually engaged with a Registered Dietitian Nutritionist (RDN) in one-on-one sessions. The primary endpoint was to examine feasibility of the program by usage of the application and feedback questions regarding the benefits and challenges of the application. Participants were predominately white (92%) and female (76%). Minimal improvements in weight and systolic blood pressure were found. Participant attitude survey data declined from 4-weeks to 12-weeks of the intervention. Interestingly though, patients in a rural clinic had lesser declines in attitudes than peri-urban participants. Qualitative feedback data identified participants predominately had a positive overall feeling toward the approach. Participants expressed favorability of RDN access, the variety of foods, but did give suggestions for in-person meetings and more updating of the application. Implementing a technology approach to nutrition in rural areas of West Virginia using a mobile application with RDN access may be one strategy to address public health issues such as obesity. Full article

(This article belongs to the Special Issue Personalized Nutrition and Diagnostic Criteria, including Serum Biomarkers, for Osteosarcopenic Obesity as a Model for Body Composition Assessment and Improvement)

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8 pages, 1309 KiB

Open AccessPerspective

A Perspective on Microneedle-Based Drug Delivery and Diagnostics in Paediatrics

by Liliana R Pires, KB Vinayakumar, Maria Turos, Verónica Miguel and João Gaspar

J. Pers. Med. 2019, 9(4), 49; https://doi.org/10.3390/jpm9040049 - 15 Nov 2019

Cited by 31 | Viewed by 7959

Abstract

Microneedles (MNs) have been extensively explored in the literature as a means to deliver drugs in the skin, surpassing the stratum corneum permeability barrier. MNs are potentially easy to produce and may allow the self-administration of drugs without causing pain or bleeding. More [...] Read more.

Microneedles (MNs) have been extensively explored in the literature as a means to deliver drugs in the skin, surpassing the stratum corneum permeability barrier. MNs are potentially easy to produce and may allow the self-administration of drugs without causing pain or bleeding. More recently, MNs have been investigated to collect/assess the interstitial fluid in order to monitor or detect specific biomarkers. The integration of these two concepts in closed-loop devices holds the promise of automated and minimally invasive disease detection/monitoring and therapy. These assure low invasiveness and, importantly, open a window of opportunity for the application of population-specific and personalised therapies. Full article

(This article belongs to the Special Issue Emerging Technologies for the Next Generation Personalized and Precision Medicine)

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10 pages, 1386 KiB

Open AccessCase Report

Role of Receptor Profiling for Personalized Therapy in a Patient with a Growth Hormone-Secreting Macroadenoma Resistant to First-Generation Somatostatin Analogues

by Krystallenia I. Alexandraki, Eirini Papadimitriou, Vasiliki Mavroeidi, Georgios Kyriakopoulos, Antonios Xydakis, Theodoros G. Papaioannou, Denise Kolomodi, Gregory A. Kaltsas and Ashley B. Grossman

J. Pers. Med. 2019, 9(4), 48; https://doi.org/10.3390/jpm9040048 - 15 Nov 2019

Cited by 6 | Viewed by 4949

Abstract

Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who [...] Read more.

Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. Methods: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. Results: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. Conclusion: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes. Full article

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13 pages, 217 KiB

Open AccessArticle

Physician Experience with Direct-To-Consumer Genetic Testing in Kaiser Permanente

by M. Cabell Jonas, Pim Suwannarat, Andrea Burnett-Hartman, Nikki Carroll, Michelle Turner, Kristen Janes, Christine Truong, Erica Blum-Barnett, Nazneen Aziz and Elizabeth A. McGlynn

J. Pers. Med. 2019, 9(4), 47; https://doi.org/10.3390/jpm9040047 - 1 Nov 2019

Cited by 16 | Viewed by 6191

Abstract

Health systems and physicians nationwide aspire to consistently and reliably apply genetic and genomic information to guide disease prevention, management, and treatment. However, clinical information, including genetics/genomics data from within and outside of the care delivery system, is expanding rapidly. Between November 2017 [...] Read more.

Health systems and physicians nationwide aspire to consistently and reliably apply genetic and genomic information to guide disease prevention, management, and treatment. However, clinical information, including genetics/genomics data from within and outside of the care delivery system, is expanding rapidly. Between November 2017 and April 2018, we surveyed 1502 Permanente Medical Group primary care and specialist physicians to assess the degree to which direct-to-consumer genetic test results were being presented to physicians and identify genetics educational needs among physicians (response rate 15%). Adjusted logistic regression (according to respondent characteristics) was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing responses within groups. Results showed 35% and 12% of respondents reported receiving at least one direct-to-consumer health risk genetic result (DTC-health risk) or direct-to-consumer pharmacogenomic test result (DTC-PGx), respectively, from a patient in the past year. Of those receiving at least one test result, 40% (DTC-health risk) and 39% (DTC-PGx) of physicians reported 1+ referral(s); 78% (DTC-health risk) and 42% (DTC-PGx) of referrals were to clinical genetics. In total, 85% of physicians would spend ≥2 h/year on genetics/genomics education. Full article

(This article belongs to the Collection Genomic Medicine and Policy)

15 pages, 616 KiB

Open AccessReview

Using the Immunophenotype to Predict Response to Biologic Drugs in Rheumatoid Arthritis

by Ben Mulhearn, Anne Barton and Sebastien Viatte

J. Pers. Med. 2019, 9(4), 46; https://doi.org/10.3390/jpm9040046 - 2 Oct 2019

Cited by 15 | Viewed by 7409

Abstract

Tumour necrosis factor (TNF)-α is a key mediator of inflammation in rheumatoid arthritis, and its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, [...] Read more.

Tumour necrosis factor (TNF)-α is a key mediator of inflammation in rheumatoid arthritis, and its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, have been developed. Not all patients respond to a biologic drug, leading to a knowledge gap between biologic therapies available and the confident prediction of response. So far, genetic studies have failed to uncover clinically informative biomarkers to predict response. Given that the targets of biologics are immune pathways, immunological study has become all the more pertinent. Furthermore, advances in single-cell technology have enabled the characterization of many leucocyte subsets. Studying the blood immunophenotype may therefore, define biomarker profiles relevant to each individual patient’s disease and treatment outcome. This review summarises our current understanding of how immune biomarkers might be able to predict treatment response to biologic drugs. Full article

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8 pages, 943 KiB

Open AccessArticle

Interaction between Fexofenadine and CYP Phenotyping Probe Drugs in Geneva Cocktail

by Marija Bosilkovska, Gaelle Magliocco, Jules Desmeules, Caroline Samer and Youssef Daali

J. Pers. Med. 2019, 9(4), 45; https://doi.org/10.3390/jpm9040045 - 2 Oct 2019

Cited by 7 | Viewed by 6404

Abstract

Drug metabolic enzymes and transporters are responsible for an important variability in drug disposition. The cocktail approach is a sound strategy for the simultaneous evaluation of several enzyme and transporter activities for a personalized dosage of medications. Recently, we have demonstrated the reliability [...] Read more.

Drug metabolic enzymes and transporters are responsible for an important variability in drug disposition. The cocktail approach is a sound strategy for the simultaneous evaluation of several enzyme and transporter activities for a personalized dosage of medications. Recently, we have demonstrated the reliability of the Geneva cocktail, combining the use of dried blood spots (DBS) and reduced dose of phenotyping drugs for the evaluation of the activity of six cytochromes and P-glycoprotein (P-gp). As part of a study evaluating potential drug–drug interactions between probe drugs of the Geneva cocktail, the present paper focuses on the impact of cytochromes (CYP) probe drugs on the disposition of fexofenadine, a P-gp test drug. In a randomized four-way Latin-square crossover study, 30 healthy volunteers (15 men and 15 women) received caffeine 50 mg, bupropion 20 mg, flurbiprofen 10 mg, omeprazole 10 mg, dextromethorphan 10 mg, midazolam 1 mg, and fexofenadine 25 mg alone (or as part of a previously validated combination) and all together (Geneva cocktail). The determination of drug concentrations was performed in DBS samples and pharmacokinetic parameters were calculated. Fexofenadine AUC_{0–8 h} and C_max decreased by 43% (geometric mean ratio: 0.57; CI 90: 0.50–0.65; p < 0.001) and 49% (geometric mean ratio: 0.51; CI 90: 0.44–0.59; p < 0.001), respectively, when fexofenadine was administered as part of the Geneva cocktail in comparison to fexofenadine alone. Consequently, the apparent oral clearance (Cl/F) increased 1.7-fold (CI 90: 1.49–1.93; p < 0.001). There was no interaction between the remaining probes. In conclusion, an unexpected interaction occurred between fexofenadine and one or several of the following substances: caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam. Further studies are necessary to elucidate the mechanism of this interaction. Full article

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J. Pers. Med., Volume 9, Issue 4 (December 2019) – 8 articles

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