scholarly journals Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 160
Author(s):  
María Celsa Peña-Martín ◽  
Belén García-Berrocal ◽  
Almudena Sánchez-Martín ◽  
Elena Marcos-Vadillo ◽  
María Jesús García-Salgado ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Adverse Events ◽  
Precision Medicine ◽  
Drug Efficacy ◽  
Response To Treatment ◽  
Individual Response ◽  
Test Results ◽  
Individualized Drug Therapy ◽  
The Individual ◽  
Multimorbid Patients

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment. Precision medicine can increase drug safety in many scenarios, including polypharmacy. In this report, we share our experience utilizing precision medicine over the past ten years. Based on our experience using pharmacogenetic (PGx)-informed prescribing, we implemented a five-step precision medicine protocol (5SPM) that includes the assessment of the biological–clinical characteristics of the patient, current and past prescription history, and the patient’s PGx test results. To illustrate our approach, we present cases highlighting the clinical relevance of precision medicine with a focus on patients with a complex history and polypharmacy.

scholarly journals Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 129 ◽  
Author(s):  
Richard D. Beger ◽  
Michael A Schmidt ◽  
Rima Kaddurah-Daouk
Keyword(s):  
Clinical Trials ◽  
Drug Treatment ◽  
Precision Medicine ◽  
Metabolic Profile ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Individual Response ◽  
Patient Response ◽  
Drug Mechanism ◽  
The Individual

Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual’s metabolic profile has been referred to as his or her “metabotype.” As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual’s pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.

scholarly journals Personalised approaches to pharmacotherapy for schizophrenia

2016 ◽  
Vol 22 (2) ◽  
pp. 78-86 ◽  
Author(s):  
John Lally ◽  
James H. MacCabe
Keyword(s):  
Medical Treatment ◽  
Antipsychotic Medication ◽  
Traditional Approach ◽  
Personalised Medicine ◽  
Individual Characteristics ◽  
Response To Treatment ◽  
Individual Response ◽  
Trial And Error ◽  
Recent Advances ◽  
The Individual

SummaryThe traditional approach to selecting antipsychotic medication involves little more than trial and error. Recent advances in genetics and molecular science offer the hope of a ‘personalised medicine’ approach to antipsychotic development and prescribing in schizophrenia. Personalised medicine is the practice of tailoring medical treatment to the individual characteristics of each patient. In schizophrenia, this will involve the identification of more homogeneous subsets of patients through the application of genetics, epigenetics, proteomics and metabolomics, neuroimaging and other biomarkers, and the use of these findings to stratify patients according to their response to treatment. In this article, we focus on the emerging evidence in pharmacogenetics and biomarkers for assessing individual response and tolerability of antipsychotic medication in schizophrenia.

scholarly journals The Host Genetic Diversity in Malaria Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Vitor R. R. de Mendonça ◽  
Marilda Souza Goncalves ◽  
Manoel Barral-Netto
Keyword(s):  
Genetic Factors ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Genetic Alterations ◽  
Response To Treatment ◽  
Individual Response ◽  
Genetic Mechanisms ◽  
Host Genetic ◽  
Different Populations ◽  
The Individual

Populations exposed toPlasmodiuminfection develop genetic mechanisms of protection against severe disease. The clinical manifestation of malaria results primarily from the lysis of infected erythrocytes and subsequent immune and inflammatory responses. Herein, we review the genetic alterations associated with erythrocytes or mediators of the immune system, which might influence malaria outcome. Moreover, polymorphisms in genes related to molecules involved in mechanisms of cytoadherence and their influence on malaria pathology are also discussed. The results of some studies have suggested that the combinatorial effects of a set of genetic factors in the erythrocyte-immunology pathway might be relevant to host resistance or susceptibility againstPlasmodiuminfection. However, these results must be interpreted with caution because of the differences observed in the functionality and frequency of polymorphisms within different populations. With the recent advances in molecular biology techniques, more robust studies with reliable data have been reported, and the results of these studies have identified individual genetic factors for consideration in preventing severe disease and the individual response to treatment.

Chronic Stress May Not Be a Factor in the Behavioral Response to Chronic Lithium in ICR Mice

Pharmacology ◽  
2018 ◽  
Vol 102 (5-6) ◽  
pp. 281-286 ◽  
Author(s):  
Gil Shemesh ◽  
Nirit Kara ◽  
Haim Einat ◽  
Keyword(s):  
Forced Swim Test ◽  
Individual Response ◽  
Test Results ◽  
Stress Control ◽  
Icr Mice ◽  
Sweet Solution ◽  
Plus Maze ◽  
Chronic Stressors ◽  
Stress Intervention ◽  
The Individual

Background: Lithium (Li) is the prototypic mood-stabilizing drug, but the individual response to Li is highly heterogeneous. Some evidence suggest interactions between Li and stress, and it is possible to hypothesize that lithium’s effects are modified by stress conditions. The current study examines the interaction between 2 chronic stressors, constant light (CL) and restrain and the behavioral responses to chronic Li in female and male mice. Methods: Female and male ICR mice were exposed to 3 weeks of either (1) CL; (2) daily restrain or (3) no stress control. One week after the start of the stress intervention, mice started chronic oral Li treatment or control. After 2 weeks of stress and Li, mice were tested in a number of behavioral tests including spontaneous activity, sweet solution preference, plus-maze and forced swim test. Results: There were no effects of stressors on behavior. Effects of Li were demonstrated in males but not females with no interactions between stress and Li. Conclusions: The behavioral effects of Li in this study were not affected by stress. The lack of effects of the stressors themselves on behavior suggests that the application of more intrusive stressors might be needed to further explore the issue.

scholarly journals Metabolomics, Microbiota, and In Vivo and In Vitro Biomarkers in Type 2 Severe Asthma: A Perspective Review

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 647
Author(s):  
Cristiano Caruso ◽  
Stefania Colantuono ◽  
Alberto Nicoletti ◽  
Stefania Arasi ◽  
Davide Firinu ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Severe Asthma ◽  
Biomarker Discovery ◽  
Drug Efficacy ◽  
Individual Variability ◽  
Individual Characteristics ◽  
Point Of View ◽  
The Individual

Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient; thus, it could be a new approach for the management of severe asthma that considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. Metabolomics is the systematic study of low molecular weight (bio)chemicals in a given biological system and offers a powerful approach to biomarker discovery and elucidating disease mechanisms. In this point of view, metabolomics could play a key role in targeting precision medicine.

scholarly journals Molecular genetic methods in biomedical research. Part III: human gene diagnostics in clinical practice

2021 ◽  
Vol 6 (3) ◽  
pp. 100-109
Author(s):  
A. N. Volkov ◽  
L. V. Nacheva
Keyword(s):  
Low Cost ◽  
Molecular Genetic ◽  
Real Life ◽  
High Sensitivity ◽  
Response To Treatment ◽  
Individual Response ◽  
Technical Simplicity ◽  
The Individual ◽  
Gene Diagnostics ◽  
Pcr Diagnostics

Application of molecular genetic methods in the diagnosis and treatment of human diseases is extremely wide due to a huge amount of hereditary information contained in the human genome. Gene diagnostics allows establishing predisposition to diseases, identification of genetic abnormalities and prediction of pathological outcomes. In addition, gene diagnostics also enables prediction of the individual response to treatment in order to achieve the maximum therapeutic effect. Among all molecular genetic methods, polymerase chain reaction (PCR) diagnostics is a leading approach. Technical simplicity, low cost, high sensitivity and reliability of the method have made PCR diagnostics a routine modality for the risk assessment, diagnostics, and monitoring of the treatment efficiency. Here, we consider the application of PCR diagnostics for the abovementioned tasks and talk about the real-life examples of detecting mutations and chromosomal aberrations which may cause a disease. Further, we discuss the prospects of using a semi-quantitative PCR in medical practice and focus on pharmacogenetics as a key component of a personalised therapy. The lecture is aimed primarily at biomedical students and physicians and represents a continuation of the previous lectures published in Fundamental and Clinical Medicin.

Effect of amiodarone on heart rate variability in patients with newly diagnosed atrial fibrillation (clinical observation)

2020 ◽  
pp. 81-85
Author(s):  
E. P. Popova ◽  
O. T. Bogova ◽  
S. N. Puzin ◽  
D. A. Sychyov ◽  
V. P. Fisenko
Keyword(s):  
Atrial Fibrillation ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Drug Therapy ◽  
Heart Function ◽  
Newly Diagnosed ◽  
Class Iii ◽  
Spectral Parameters ◽  
Patient Will ◽  
The Individual

Spectral analysis of heart rate variability gives an idea of the role of the autonomic nervous system in the regulation of chronotropic heart function. This method can be used to evaluate the effectiveness of drug therapy. Drug therapy should be carried out taking into account the individual clinical form of atrial fibrillation. Information about the vegetative status of the patient will undoubtedly increase the effectiveness of treatment. In this study, spectral parameters were studied in patients with newly diagnosed atrial fibrillation. The effect of antiarrhythmic drug class III amiodarone on the spectral parameters of heart rate variability was studied.

Is it Worth CANVASing for CREDENCE? A Benefit-risk Analysis

2020 ◽  
Vol 16 (5) ◽  
pp. 509-514
Author(s):  
Binayak Sinha ◽  
Samit Ghosal
Keyword(s):  
Adverse Events ◽  
Fungal Infections ◽  
Absolute Risk ◽  
Pooled Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Pooled Data ◽  
The Individual ◽  
Fracture Risks ◽  
Number Needed To Harm

Background and Aims: A number of significant positive and negative signals emerged from the CANVAS Program and CREDENCE trial with the use of canagliflozin. These signals are confusing. A Likelihood of being Helped of Harmed (LHH) analysis was conducted to determine the risk, benefit ratio associated with canagliflozin use and address the signals as a continuum. Materials &Methods: LHH was calculated from the number needed to treat (NNT) and number needed to harm (NNH) available from the absolute risk reductions reported with the outcomes of interest, in these two trials. Results: In the CANVAS Program, LHH for major adverse cardiovascular events (MACE) points at a significant benefit with canagliflozin use in comparison to amputation (1.65), fractures (1.65) and euglycaemic diabetic ketoacidosis (euDKA) (16.67) risks. Only genital fungal infections were significant more in both sexes (0.21-M and 0.1-F) when LHH was matched against the positive outcomes. In contrast, the hHF benefits were outweighed by amputation (0.95) and fracture risks (0.95). : In CREDENCE trial, the LHH for Primary composite, Renal composite and MACE, all supported the benefits in comparison to any adverse events encountered in the trial. : The LHH from pooled data (CANVAS Program and CREDENCE trial) was in favour of all the benefits (hHF and renal composites) except for MACE matched against amputation (0.66). Conclusion: The outcome benefits were in favour of canagliflozin in comparison to all reported adverse events, when hHF and renal composite were under consideration, in both the individual and pooled LHH analysis. However, the MACE benefits were overwhelmed by amputation risk in the pooled analysis.

scholarly journals Children’s Astronomy. Development of the Shape of the Earth Concept in Polish Children between 5 and 10 Years of Age

2021 ◽  
Vol 11 (2) ◽  
pp. 75
Author(s):  
Jan Amos Jelinek
Keyword(s):  
Mental Model ◽  
Cultural Influences ◽  
Test Results ◽  
The Earth ◽  
Spherical Earth ◽  
The Individual ◽  
High Level ◽  
Cognitive Problems ◽  
Teaching Situations ◽  
Model Approach

The Earth’s shape concept develops as consecutive cognitive problems (e.g., the location of people and trees on the spherical Earth) are gradually resolved. Establishing the order of problem solving may be important for the organisation of teaching situations. This study attempted to determine the sequence of problems to be resolved based on tasks included in the EARTH2 test. The study covered a group of 444 children between 5 and 10 years of age. It captured the order in which children solve cognitive problems on the way to constructing a science-like concept. The test results were compared with previous studies. The importance of cultural influences connected to significant differences (24%) in test results was emphasised. Attention was drawn to the problem of the consistency of the mental model approach highlighted in the literature. The analysis of the individual sets of answers provided a high level of consistency of indications referring to the same model (36%), emphasising the importance of the concept of mental models.

P2Y12 inhibitors in neuroendovascular surgery: An opportunity for precision medicine

2021 ◽  
pp. 159101992199139
Author(s):  
Axel Rosengart ◽  
Malie K Collins ◽  
Philipp Hendrix ◽  
Ryley Uber ◽  
Melissa Sartori ◽  
...  
Keyword(s):  
Adverse Events ◽  
Precision Medicine ◽  
Point Of Care ◽  
Indirect Evidence ◽  
Cost Benefit ◽  
Interventional Cardiology ◽  
Platelet Inhibition ◽  
Response Monitoring ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors

Introduction Dual antiplatelet therapy (DAPT), primarily the combination of aspirin with a P2Y12 inhibitor, in patients undergoing intravascular stent or flow diverter placement remains the primary strategy to reduce device-related thromboembolic complications. However, selection, timing, and dosing of DAPT is critical and can be challenging given the existing significant inter- and intraindividual response variations to P2Y12 inhibitors. Methods Assessment of indexed, peer-reviewed literature from 2000 to 2020 in interventional cardiology and neuroendovascular therapeutics with critical, peer-reviewed appraisal and extraction of evidence and strategies to utilize DAPT in cardio- and neurovascular patients with endoluminal devices. Results Both geno- and phenotyping for DAPT are rapidly and conveniently available as point-of-care testing at a favorable cost-benefit ratio. Furthermore, systematic inclusion of a quantifying clinical risk score combined with an operator-linked, technical risk assessment for potential adverse events allows a more precise and individualized approach to new P2Y12 inhibitor therapy. Conclusions The latest evidence, primarily obtained from cardiovascular intervention trials, supports that combining patient pharmacogenetics with drug response monitoring, as part of an individually tailored, precision medicine approach, is both predictive and cost-effective in achieving and maintaining individual target platelet inhibition levels. Indirect evidence supports that this gain in optimizing drug responses translates to reducing main adverse events and overall treatment costs in patients undergoing DAPT after intracranial stent or flow diverting treatment.

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