BioDWH2: an automated graph-based data warehouse and mapping tool.

J Integr Bioinform. 2021 Feb 22;:

Authors: Friedrichs M

Abstract
Data integration plays a vital role in scientific research. In biomedical research, the OMICS fields have shown the need for larger datasets, like proteomics, pharmacogenomics, and newer fields like foodomics. As research projects require multiple data sources, mapping between these sources becomes necessary. Utilized workflow systems and integration tools therefore need to process large amounts of heterogeneous data formats, check for data source updates, and find suitable mapping methods to cross-reference entities from different databases. This article presents BioDWH2, an open-source, graph-based data warehouse and mapping tool, capable of helping researchers with these issues. A workspace centered approach allows project-specific data source selections and Neo4j or GraphQL server tools enable quick access to the database for analysis. The BioDWH2 tools are available to the scientific community at https://github.com/BioDWH2.

PMID: 33618440 [PubMed - as supplied by publisher]

ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine.

Mol Biol Rep. 2021 Feb 22;:

Authors: Juan-Carlos PM, Perla-Lidia PP, Stephanie-Talia MM, Mónica-Griselda AM, Luz-María TE

Abstract
The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.

PMID: 33616835 [PubMed - as supplied by publisher]

Corrigendum: Bevacizumab Plus FOLFOX-4 Combined With Deep Electro-Hyperthermia as First-line Therapy in Metastatic Colon Cancer: A Pilot Study.

Front Oncol. 2020;10:637880

Authors: Ranieri G, Laface C, Laforgia M, De Summa S, Porcelli M, Macina F, Ammendola M, Molinari P, Lauletta G, Di Palo A, Rubini G, Ferrari C, Gadaleta CD

Abstract
[This corrects the article .].

PMID: 33614511 [PubMed]

Pharmacogenetics of sulfonylurea: Presence of CYP2C9*2, CYP2C9*3 and a novel allele, CYP2C9*61, in Type 2 diabetes patients under sulfonylurea therapy.

Pak J Pharm Sci. 2020 Jul;33(4(Supplementary)):1771-1777

Authors: Muhammad SD, Khan H, Hussain M, Zeb TF, Kumar D, Rahi R, Asif M, Balooch AA

Abstract
CYP2C9 is an important member of the cytochrome P450 gene family involved in the metabolism of 15% of the drugs including an oral antidiabetic agent sulfonylurea. This study aims to investigate the frequency of CYP2C9*2 and CYP2C9*3 alleles of the gene in the sulfonylurea treated diabetic subjects in Pakistan. Briefly, total 105 patients were included in the study and segregated as control (24) and test (81) based on the clinical manifestations after taking sulfonylurea. Genomic DNA was extracted from blood of the subjects and amplified using CYP2C9 specific primers for exon 3 and exon 7 and then subjected to DNA sequencing. Alignment of the sequences with the reference sequence shows presence of CYP2C9*3/*3, CYP2C9*1/*3 and CYP2C9*1/*2 genotypes in the test cases but only the latter two were found in the control cases. In addition a novel allele, CYP2C9*61 in the heterozygous state, was also identified frequently in the test cases. Molecular structure comparison also showed variations in the structural features of protein encoded by the allelic variants. To the best of our knowledge, the present data is the first report for CYP2C9 allelic variations in the indigenous diabetic subjects and also report the existence of novel allelic variant of CYP2C9, CYP2C9*61.

PMID: 33612460 [PubMed - in process]

Drug Saf. 2021 Feb 23. doi: 10.1007/s40264-021-01050-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Medication-related harm represents a significant issue for patient safety and quality of care. One strategy to avoid preventable adverse drug events is to utilize patient-specific factors such as pharmacogenomics (PGx) to individualize therapy.

OBJECTIVE: We measured the number of patients enrolled in a health-system biobank with actionable PGx results who received relevant medications and assessed the incidence of adverse drug events (ADEs) that might have been prevented had the PGx results been used to inform prescribing.

METHODS: Patients with actionable PGx results in the following four genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines were identified: HLA-A*31:01, HLA-B*15:02, TPMT, and VKORC1. The patients who received interacting medications (carbamazepine, oxcarbazepine, thiopurines, or warfarin) were identified, and electronic health records were reviewed to determine the incidence of potentially preventable ADEs.

RESULTS: Of 36,424 patients with PGx results, 2327 (6.4%) were HLA-A*31:01 positive; 3543 (9.7%) were HLA-B*15:02 positive; 2893 (7.9%) were TPMT intermediate metabolizers; and 4249 (11.7%) were homozygous for the VKORC1 c.1639 G>A variant. Among patients positive for one of the HLA variants who received carbamazepine or oxcarbazepine (n = 92), four (4.3%) experienced a rash that warranted drug discontinuation. Among the TPMT intermediate metabolizers who received a thiopurine (n = 56), 11 (19.6%) experienced severe myelosuppression that warranted drug discontinuation. Among patients homozygous for the VKORC1 c.1639 G>A variant who received warfarin (n = 379), 85 (22.4%) experienced active bleeding and/or international normalized ratio (INR) > 5 that warranted drug discontinuation or dose reduction.

CONCLUSION: Patients with actionable PGx results from a health-system biobank who received relevant medications experienced predictable ADEs. These ADEs may have been prevented if the patients' PGx results were available in the electronic health record with clinical decision support prior to prescribing.

PMID:33620701 | DOI:10.1007/s40264-021-01050-6

Clin Transl Sci. 2021 Feb 23. doi: 10.1111/cts.12981. Online ahead of print.

ABSTRACT

Consensus guidelines exist for genotype-guided fluoropyrimidine dosing based on variation in the gene dihydropyrimidine dehydrogenase (DPYD). However, these guidelines have not been widely implemented in North America and most studies of pretreatment DPYD screening have been conducted in Europe. Given regional differences in treatment practices and rates of adverse events (AEs), we investigated the impact of pretreatment DPYD genotyping on AEs in a Canadian context. Patients referred for DPYD genotyping prior to fluoropyrimidine treatment were enrolled from December 2013 through November 2019 and followed until completion of fluoropyrimidine treatment. Patients were genotyped for DPYD c.1905+1G>A, c.2846A>T, c.1679T>G, and c.1236G>A. Genotype-guided dosing recommendations were informed by Clinical Pharmacogenetics Implementation Consortium guidelines. The primary outcome was the proportion of patients who experienced a severe fluoropyrimidine-related AE (grade ≥3, Common Terminology Criteria for Adverse Events version 5.0). Secondary outcomes included early severe AEs, severe AEs by toxicity category, discontinuation of fluoropyrimidine treatment due to AEs, and fluoropyrimidine-related death. Among 1394 patients, mean (SD) age was 64 (12) years, 764 (54.8%) were men, and 47 (3.4%) were DPYD variant carriers treated with dose reduction. Eleven variant carriers (23%) and 418 (31.0%) noncarriers experienced a severe fluoropyrimidine-related AE (p = 0.265). Six carriers (15%) and 284 noncarriers (21.1%) experienced early severe fluoropyrimidine-related AEs (p = 0.167). DPYD variant carriers treated with genotype-guided dosing did not experience an increased risk for severe AEs. Our data support a role for DPYD genotyping in the use of fluoropyrimidines in North America.

PMID:33620159 | DOI:10.1111/cts.12981

Pharmacogenomics. 2021 Feb 23. doi: 10.2217/pgs-2021-0011. Online ahead of print.

NO ABSTRACT

PMID:33619995 | DOI:10.2217/pgs-2021-0011

NPJ Vaccines. 2021 Feb 22;6(1):28. doi: 10.1038/s41541-021-00292-w.

ABSTRACT

The new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

PMID:33619260 | DOI:10.1038/s41541-021-00292-w

Cancer Res. 2021 Feb 22:canres.2297.2020. doi: 10.1158/0008-5472.CAN-20-2297. Online ahead of print.

ABSTRACT

Fusion genes including NPM-ALK can promote T cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM-ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T cell effector programs, re-emergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM-ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Lastly, TCR-generated signals were required to achieve T cell transformation, explaining how healthy individuals can harbor T cells with NPM-ALK translocations. These findings describe the fundamental mechanisms of NPM-ALK-mediated oncogenesis, and may serve as a model to better understand factors that regulate tumor formation.

PMID:33619116 | DOI:10.1158/0008-5472.CAN-20-2297

Clin Mol Hepatol. 2021 Feb 23. doi: 10.3350/cmh.2020.0162. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients.

METHODS: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded.

RESULTS: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P < 0.05). During a mean follow-up of 89 months, 32 (19.4%) patients experienced at least one clinical outcome (cardiovascular events, n = 22; liver-related complications, n = 6; extra-hepatic malignancy, n = 5; and mortality, n = 6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR] = 0.004, 95% confidence interval [CI]: 0.00-0.64, P = 0.033 and HR = 0.01, 95% CI: 0.00-0.97, P = 0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese.

CONCLUSION: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

PMID:33618508 | DOI:10.3350/cmh.2020.0162

CYP2C19 Loss-of-Function Associated with First-Time Ischemic Stroke in Non-surgical Asymptomatic Carotid Artery Stenosis During Clopidogrel Therapy.

Transl Stroke Res. 2021 Feb 21;:

Authors: Patel PD, Niu X, Shannon CN, Denny JC, Peterson JF, Fusco MR, Chitale RV

Abstract
This study measures effect of CYP2C19 genotype on ischemic stroke risk during clopidogrel therapy for asymptomatic, extracranial carotid stenosis patients. Using deidentified electronic health records, patients were selected for retrospective cohort using administrative code for carotid stenosis, availability of CYP2C19 genotype result, clopidogrel exposure, and established patient care. Patients with intracranial atherosclerosis, aneurysm, arteriovenous malformation, prior ischemic stroke, or observation time <1 month were excluded. Dual antiplatelet therapy patients were included. Patients with carotid endarterectomy or stenting were analyzed in a separate subgroup. Time-to-event analysis using Cox regression was conducted to model ischemic stroke events based on CYP2C19 loss-of-function allele and adjusted with the most predictive covariates from univariate analysis. Covariates included age, gender, race, length of aspirin, length of concurrent antiplatelet/anticoagulant treatment, diabetes, coagulopathy, hypertension, heart disease, atrial fibrillation, and lipid disorder. A total of 1110 patients met selection criteria for medical therapy cohort (median age 68 [interquartile range (IQR) 60-75] years, 64.9% male, 91.9% Caucasian). Median study period was 2.8 [0.8-5.3] years. A total of 47 patients (4.2%) had an ischemic stroke event during study period. CYP2C19 loss-of-function allele was strongly associated with ischemic stroke events (one allele: HR 2.3, 95% CI 1.1-4.7, p=0.020; two alleles: HR 10.2, 95% CI 2.8-36.8, p<0.001) after adjustment. For asymptomatic carotid stenosis patients receiving clopidogrel to prevent ischemic stroke, CYP2C19 loss-of-function allele is associated with 2- to 10-fold increased risk of ischemic stroke. CYP2C19 genotype may be considered when selecting antiplatelet therapy for stroke prophylaxis in non-procedural, asymptomatic carotid stenosis.

PMID: 33611730 [PubMed - as supplied by publisher]

Tissue adhesives for peripheral intravenous catheter securement: A prospective randomized controlled pilot trial.

Am J Emerg Med. 2021 Feb 01;44:128-131

Authors: Lešnik A, Gorenjak M, Žumer S, Zorčič V, Mišanović Ž, Majhenič M, Podstenšek A, Toplak M, Fekonja U, Markota A

Abstract
BACKGROUND: In some patients securing the peripheral intravenous cannula (PIVC) with a standard adhesive dressing can be difficult because of sweat or other body fluids. The aim of our study was to evaluate the use of tissue adhesives alone as a means to secure PIVCs inserted in the emergency department.
METHODS: We performed a prospective interventional pilot study from November 2019 to May 2020 in a medical emergency department of an urban tertiary hospital. Patients were randomized to two groups: tissue adhesives (TA) or adhesive dressing (AD) group. After randomization we followed them until day 4.
RESULTS: There were no significant differences between TA and AD groups in the rate of unplanned removal of PIVCs in the first 72 h (57.1% vs. 45.8%, p = 0.29), the rate of unplanned removal of PIVCs in the ED (0% vs. 2.1%, p = 1.00), the rate of unplanned removal of PIVC in the first 24 h (42.8% vs. 35.4%, p = 0.52), as well as in the rate of phlebitis (7.1% vs. 14.6%, p = 0.34) and the rate of any blood-stream infection (0% vs. 0%, p = 1.00).
CONCLUSION: We did not observe any significant differences when PIVCs inserted in the emergency department were secured with tissue adhesives alone, compared to standard adhesive dressings. We observed a high rate of unplanned removal of PIVCs, necessitating further research to determine more reliable ways of securing PIVCs.

PMID: 33610080 [PubMed - as supplied by publisher]

A systematic review and meta-analysis of genotype-based and individualized data analysis of SLCO1B1 gene and statin-induced myopathy.

Pharmacogenomics J. 2021 Feb 19;:

Authors: Turongkaravee S, Jittikoon J, Lukkunaprasit T, Sangroongruangsri S, Chaikledkaew U, Thakkinstian A

Abstract
This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.

PMID: 33608664 [PubMed - as supplied by publisher]

Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder.

Pharmacogenomics J. 2021 Feb 19;:

Authors: Zastrozhin MS, Skryabin VY, Petukhov AE, Torrado MV, Pankratenko EP, Zastrozhina AK, Grishina EA, Ryzhikova KA, Shipitsyn VV, Bryun EA, Sychev DA

Abstract
Citalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681G>A polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age-38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p < 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p < 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p < 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.

PMID: 33608663 [PubMed - as supplied by publisher]

The prevalence and clinical relevance of 2R/2R TYMS genotype in patients with gastrointestinal malignancies treated with fluoropyrimidine-based chemotherapy regimens.

Pharmacogenomics J. 2021 Feb 19;:

Authors: Khushman M, Patel GK, Maharjan AS, McMillin GA, Nelson C, Hosein P, Singh AP

Abstract
INTRODUCTION: The prevalence of 2R/2R TYMS genotype is variable but estimated to be around 20-30% in Caucasians. The clinical relevance of TYMS 2R/2R genotype in predicting severe fluoropyrimidine-related adverse events (FrAE) is controversial. Here, we explored the prevalence and clinical relevance of 2R/2R TYMS genotype.
METHODS: Between 2011 and 2018, 126 patients were genotyped for TYMS. FrAEs were graded according to CTCAE version 5.0. Fisher's exact test was used for statistical analysis.
RESULTS: The prevalence of TYMS 2R/2R genotype was 24.6%. Among patients with TYMS genotypes (N = 71) that predict decreased TS expression, 2R/2R TYMS genotype was the most common TYMS genotype seen in female (57%) and African American (60%) patients. Among patients with genotypes that predict increased TS expression (N = 55), 12 patients had grade 3-4 FrAEs (22%), while among patients with genotypes that predict decreased TS expression (N = 71), 30 patients had grade 3-4 FrAEs (42%) (p = 0.0219). Compared to patients with genotypes predicting increased TS expression, 17 out of 31 patients (55%) with TYMS 2R/2R genotype had grade 3-4 FrAEs (p = 0.0039) and 15 out 40 patients (38%) with TYMS 2R/3RC and TYMS 3RC/3RC genotype had grade 3-4 FrAEs (p = 0.1108).
CONCLUSION: The prevalence of TYMS 2R/2R genotype was 24.6%, and it had a unique sex and ethnic distribution. Polymorphism in the promoter region of TYMS gene that predicts decreased TS expression due to 2R/2R variant was associated with grade 3-4 FrAEs. These data suggest that genotyping patients who are not DPD deficient for TYMS might identify patients at risk of severe FrAEs.

PMID: 33608662 [PubMed - as supplied by publisher]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2021/02/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Clin Res Hepatol Gastroenterol. 2021 Feb 16;45(2):101589. doi: 10.1016/j.clinre.2020.101589. Online ahead of print.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) incidence and related-deaths are increasing worldwide. PDAC is characterized by poor prognosis due to late diagnosis, high metastatic capacity and resistance to therapy. This is partially due to its specific microenvironment, where the stroma is prominent over tumor cells. Besides the oral and gut microbiota, the intratumor microbiome, i.e. the bacterial and fungal microorganisms present within the tumor, was recently introduced as a new partner of the tumor microenvironment of PDAC modulating pancreatic carcinogenesis, intratumor immune infiltrates, and response to chemotherapy. In this review, we propose an overview of current knowledge about the roles of bacteria and fungi in PDAC development and biology, and discuss potential therapeutic implications.

PMID:33607375 | DOI:10.1016/j.clinre.2020.101589

Cancer Med. 2021 Feb 19. doi: 10.1002/cam4.3788. Online ahead of print.

ABSTRACT

BACKGROUND: The long-term consequences of chemotherapy and radiotherapy result in a high prevalence and early onset of age-related chronic diseases in survivors. We aimed to examine whether childhood and adolescent cancer survivors (CS) demonstrate biomarkers of accelerated aging.

METHODS: We evaluated 50 young adult CS at 11 [8-15] years after cancer diagnosis, and 30 healthy, age and sex-matched controls, who were unexposed to cancer therapy. Using a machine-learning approach, we assessed factors discriminating CS from controls and compared selected biomarkers and lymphocyte subpopulations with data from the Framingham Heart Study (FHS) cohort and the Genotype Tissue Expression (GTEx) project.

RESULTS: Survivors compared with controls had higher levels of C-reactive protein and fibrinogen. The surface expression of CD38 on T cells was increased, and there was an increase in the percentage of memory T cells in survivors, compared with the unexposed group. The relationships between above cell subpopulations and age were consistent in CS, FHS, and GTEx cohorts, but not in controls.

CONCLUSIONS: Young pediatric cancer survivors differ from age-related controls in terms of activation of the adaptive immune system and chronic, low-grade inflammation. These changes resemble aging phenotype observed in older population. Further research in biomarkers of aging in young, adult childhood cancer survivors is warranted, as it may facilitate screening and prevention of comorbidities in this population.

PMID:33605556 | DOI:10.1002/cam4.3788

Saudi Pharm J. 2021 Jan;29(1):53-58. doi: 10.1016/j.jsps.2020.12.006. Epub 2020 Dec 30.

ABSTRACT

BACKGROUND: Integrating pharmacogenetics (PGx) testing into clinical practice leads to personalized medicine, which improves treatments' efficacy and safety. Successful implementation of such a service requires sufficient knowledge, perception, and self-confidence among healthcare providers, especially pharmacists.

OBJECTIVES: To evaluate governmental hospital pharmacists' knowledge, perception, and self-confidence toward PGx testing in Jeddah, Kingdom of Saudi Arabia.

METHOD: This cross-sectional study was conducted using previously validated questionnaire. Pharmacists working in five randomly selected general governmental hospitals in Jeddah between August and October 2019 were interviewed. Comparative and descriptive analyses were used to analyze the data, and the significance level was at P-value < 0.05.

RESULTS: A total of 119 pharmacists with a mean (±SD) age of 31.2 (±5.05) years were included with a response rate of 79.3%. The average total mean (±SD) score for PGx knowledge-based questions was low (2.4 ± 1.09 out of 5). Most of the participants, with a total mean score of (10.1 ± 1.6 out of 12), revealed a positive perception toward PGx testing and its implications. A moderate self-confidence score for utilizing PGx testing (4.3 ± 2.3 out of 8) was observed among the participants. Pharmacists who had completed postgraduate studies had a statistically higher mean knowledge score (P = 0.006) compared with pharmacists with undergraduate degrees.

CONCLUSION: Governmental hospital pharmacists have limited knowledge and understanding about PGx testing; however, the majority expressed a high level of awareness and agreed that PGx testing is a valuable tool for enhancing drug efficacy and safety. The study also highlighted the importance of improving pharmacists' knowledge about PGx testing, which will help them in implementing such a valuable service into their clinical practice in Saudi hospitals.

PMID:33603539 | PMC:PMC7873749 | DOI:10.1016/j.jsps.2020.12.006

Pharmgenomics Pers Med. 2021 Feb 11;14:229-237. doi: 10.2147/PGPM.S281645. eCollection 2021.

ABSTRACT

BACKGROUND: The use of pharmacogenomics data is increasing in clinical practice. However, it is unknown if pharmacogenomics data can be used more broadly to predict outcomes like hospitalization or emergency department (ED) visit. We aim to determine the association between selected pharmacogenomics phenotypes and hospital utilization outcomes (hospitalization and ED visits).

METHODS: This cohort study utilized 10,078 patients from the Mayo Clinic Biobank in the RIGHT protocol with sequence and interpreted phenotypes for 10 selected pharmacogenes including CYP2D6, CYP2C9, CYP2C19, CYP3A5, HLA B 5701, HLA B 5702, HLA B 5801, TPMT, SLCO1B1, and DPYD. The primary outcome was hospitalization with ED visits as a secondary outcome. We used Cox proportional hazards model to test the association between each pharmacogenomics phenotype and the risk of the outcomes.

RESULTS: During the follow-up period (median [in years] = 7.3), 13% (n=1354) and 8% (n=813) of the subjects experienced hospitalization and ED visits, respectively. Compared to subjects who did not experience hospitalization, hospitalized patients were older (median age [in years]: 67 vs 65), poorer self-rated health (15% vs 4.7% for fair/poor), and higher disease burden (median number of chronic conditions: 7 vs 4) at baseline. There was no association of hospitalization with any of the pharmacogenomics phenotypes. The pharmacogenomics phenotypes were not associated with disease burden, a well-established risk factor for hospital utilization outcomes. Similar findings were observed for patients with ED visits during the follow-up period.

CONCLUSION: We found no association of 10 well-established pharmacogenomics phenotypes with either hospitalization or ED visits in this relatively large biobank population and outside the context of specific drug use related to these genes. Traditional risk factors for hospitalization like age and self-rated health were much more likely to predict hospitalization and/or ED visits than this pharmacogenomics information.

PMID:33603442 | PMC:PMC7886254 | DOI:10.2147/PGPM.S281645