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Genetic Determinants of Drug Response

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1. Energy metabolism is co-determined by genetic variants in chronic lymphocytic leukemia and influences drug sensitivity. (PubMed)

Energy metabolism is co-determined by genetic variants in chronic lymphocytic leukemia and influences drug sensitivity. Chronic lymphocytic leukemia cells have an altered energy metabolism compared to normal B cells. While there is growing understanding of the molecular heterogeneity of the disease, the extent of metabolic heterogeneity and its relation to molecular heterogeneity has not been systematically studied. Here, we assessed 11 bioenergetic features, primarily reflecting cell's (...) oxidative phosphorylation and glycolytic activity, in leukemic cells from 140 chronic lymphocytic leukemia patients using metabolic flux analysis. We surveyed these bioenergetic features for relationships with molecular profiles (including genetic aberrations, transcriptome and methylome profiles) of the tumors, their ex vivo responses to a panel of 63 compounds, and with clinical data. We observed that leukemic cells with mutated immunoglobulin variable heavy-chain show significantly lower glycolytic

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2019 Haematologica

2. Genetic Determinants of Drug Response

Genetic Determinants of Drug Response Genetic Determinants of Drug Response Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Genetic (...) Determinants of Drug Response Genetic Determinants of Drug Response Aka: Genetic Determinants of Drug Response , Pharmacogenomics , Pharmacogenetics II. Definition as it relates to medication response III. Examples: Cytochrome P450 genetic variants Variants Poor metabolizers (5-10%) No response (or reduced response) to , and risk of toxicity , , risk of toxicity (reduce starting dose by 50%) ( ) risk of toxicity (reduce starting dose) ( ) risk of toxicity (reduce starting dose) Ultra-metabolizers (1-2

2018 FP Notebook

3. Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study.

Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study. Recent research suggests that genetic variants in the tumor necrosis factor receptor 2 (TNFRSF1B) gene may have an impact on susceptibility to rheumatoid arthritis (RA) and drug response. The present population-based case-control study was carried out to evaluate whether 5 tagging single-nucleotide polymorphisms (SNPs) within the TNFRSF1B gene are associated (...) the risk of RA, but does not provide strong evidence of an impact of TNFRSF1B variants in determining response to anti-TNF drugs.

2018 Pharmacogenetics and genomics

4. Genome-wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy. (PubMed)

Genome-wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy. With the exception of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDTs) are unknown. We aimed to determine whether common variation across the genome influences the response to KDT for epilepsy.We genotyped individuals who were negative for glucose transporter type 1 deficiency syndrome or other metabolic disorders (...) , who received KDT for epilepsy. Genotyping was performed with the Infinium HumanOmniExpressExome Beadchip. Hospital records were used to obtain demographic and clinical data. KDT response (≥50% seizure reduction) at 3-month follow-up was used to dissect out nonresponders and responders. We then performed a genome-wide association study (GWAS) in nonresponders vs responders, using a linear mixed model and correcting for population stratification. Variants with minor allele frequency <0.05 and those

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2018 Epilepsia

5. Genetic and Epigenetic Determinants of Response to Fluorouracil-based Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer

Genetic and Epigenetic Determinants of Response to Fluorouracil-based Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer Genetic and Epigenetic Determinants of Response to Fluorouracil-based Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study (...) Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Genetic and Epigenetic Determinants of Response to Fluorouracil-based Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care

2017 Clinical Trials

6. Genetic and epigenetic determinants of inter-individual variability in responses to toxicants (PubMed)

Genetic and epigenetic determinants of inter-individual variability in responses to toxicants It is well established that genetic variability has a major impact on susceptibility to common diseases, responses to drugs and toxicants, and influences disease-related outcomes. The appreciation that epigenetic marks also vary across the population is growing with more data becoming available from studies in humans and model organisms. In addition, the links between genetic variability, toxicity (...) that can be feasibly performed to interrogate multiple individuals, exposures, tissue types and toxicity phenotypes. We propose that among the many possible epigenetic experimental methodologies, assessment of chromatin accessibility coupled with total RNA levels provides a cost-effective and comprehensive option to sufficiently characterize the complexity of epigenetic and regulatory activity in the context of understanding the inter-individual variability in responses to toxicants.

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2017 Current opinion in toxicology

7. Developing a genetic signature to predict drug response in ovarian cancer (PubMed)

Developing a genetic signature to predict drug response in ovarian cancer There is a lack of personalized treatment options for women with recurrent platinum-resistant ovarian cancer. Outside of bevacizumab and a group of poly ADP-ribose polymerase inhibitors, few options are available to women that relapse. We propose that efficacious drug combinations can be determined via molecular characterization of ovarian tumors along with pre-established pharmacogenomic profiles of repurposed compounds (...) . To that end, we selectively performed multiple two-drug combination treatments in ovarian cancer cell lines that included reactive oxygen species inducers and HSP90 inhibitors. This allowed us to select cell lines that exhibit disparate phenotypes of proliferative inhibition to a specific drug combination of auranofin and AUY922. We profiled altered mechanistic responses from these agents in both reactive oxygen species and HSP90 pathways, as well as investigated PRKCI and lncRNA expression in ovarian

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2017 Oncotarget

8. A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension

A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more (...) . A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension (GENRES) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our for details. ClinicalTrials.gov Identifier: NCT03276598 Recruitment Status : Completed First Posted : September 8, 2017 Last Update Posted : September 11, 2017 Sponsor: Helsinki University Central Hospital

2017 Clinical Trials

9. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity (PubMed)

and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual (...) Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed

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2017 PLoS neglected tropical diseases

10. Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria (PubMed)

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer (...) of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed

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2016 Genetics

11. Guidelines on the public health response to pretreatment HIV drug resistance

12 2 METHODS 14 2.1 Methods of developing the guidelines 15 2.2 Evidence assessment 16 2.3 Interpretation of the certainty of the evidence 19 2.4 Determining the direction and strength of a recommendation 20 2.5 Information sources 21 2.6 Process of formulating recommendations and consensus statement 22 2.7 External review 23 2.8 Declaration of interests 24GUIDELINES ON THE PUBLIC HEALTH RESPONSE TO PRETREATMENT HIV DRUG RESISTANCE iv 3 PUBLIC HEALTH RESPONSE TO PRETREATMENT HIV DRUG RESISTANCE (...) of HIV PrEP pre-exposure prophylaxis QALY quality-adjusted life-year RAL raltegravir RTV ritonavir TB tuberculosis TDF tenofovir disoproxil fumarate UNAIDS Joint United Nations Programme on HIV/AIDS XTC 3TC (lamivudine) or FTC (emtricitabine)GUIDELINES ON THE PUBLIC HEALTH RESPONSE TO PRETREATMENT HIV DRUG RESISTANCE vi DEFINITIONS HIV drug resistance (HIVDR) is caused by a change (mutation) in the genetic structure of HIV that affects the ability of a particular drug or combination of drugs to block

2017 World Health Organisation HIV Guidelines

12. What is the effectiveness of genetic testing in determining the aetiology of epilepsy?

What is the effectiveness of genetic testing in determining the aetiology of epilepsy? Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites (...) or drug class or dose) and effect size. They should be considered hypothesis-generating. Ideally, a threshold describing the number of studies per subgroup required for analysis should be specified. For further guidance please refer to the and to pre-clinical meta-analysis. Example: The following study characteristics will be examined as potential source of heterogeneity: species (stratified per species); sex (stratified per sex); duration of index ischemia (linear); stem cell dose (linear); blinding

2019 PROSPERO

13. Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models (PubMed)

Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants (...) have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., 'treated-only design', statistical power) and we will discuss how specifically drug-gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression.

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2016 Pharmacogenomics

14. Impact of Genetic Polymorphism on Drug-Drug Interactions Involving CYP2D6

of Genetic Polymorphism on Drug-Drug Interactions Involving CYP2D6 The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our for details. ClinicalTrials.gov Identifier: NCT03054220 Recruitment Status : Unknown Verified February 2017 by Jules Desmeules, University Hospital, Geneva. Recruitment status was: Active, not recruiting First Posted : February 15, 2017 (...) Last Update Posted : February 15, 2017 Sponsor: Jules Desmeules Information provided by (Responsible Party): Jules Desmeules, University Hospital, Geneva Study Details Study Description Go to Brief Summary: CYP2D6 is characterized by a huge variability in the general population, mainly because of genetic polymorphism and drug-drug interactions (DDIs). CYP2D6 genotype is known to have an impact on the extent of DDIs. Indeed several studies have pointed out differential DDIs extent according

2017 Clinical Trials

15. Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review

Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review Comparative Effectiveness Review Number 218 RComparative Effectiveness Review Number 218 Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 (...) . Timothy J. Wilt, M.D., M.P.H. AHRQ Publication No. 19-EHC016-EF April 2019 ii Key Messages Purpose of Review To summarize the effects of long-term osteoporosis drug treatment and of osteoporosis drug treatment discontinuation and holidays. Key Messages • Evidence on the effects of long-term osteoporosis drug treatment and drug continuation versus discontinuation is mostly limited to white, healthy, postmenopausal women. • Long-term alendronate reduces radiographic vertebral and nonvertebral fractures

2019 Effective Health Care Program (AHRQ)

16. Genomic Determinants and Shared Genetic Pathways of Periodontal Disease

Determinants and Shared Genetic Pathways of Periodontal Disease The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT03437798 Recruitment Status : Recruiting First Posted : February 19, 2018 Last Update Posted : September 14, 2018 (...) Genomic Determinants and Shared Genetic Pathways of Periodontal Disease Genomic Determinants and Shared Genetic Pathways of Periodontal Disease - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Genomic

2018 Clinical Trials

17. Genetic Factors and Immunological Determinism of Persistent Consequences of Chikungunya

before adding more. Genetic Factors and Immunological Determinism of Persistent Consequences of Chikungunya (CHIKGENE) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT03690648 Recruitment Status : Recruiting First Posted (...) of global research on this disease. The idea of genetic determinism of the clinical expression of infectious diseases has been supported by many epidemiological arguments over the past fifty years. The identification of genetic variants, associated with a disease, often allows a better understanding of the molecular mechanisms involved with consequent significant benefits such as the development of specific biomarkers for new preventive (vaccination) and / or therapeutic (drug design) approaches

2018 Clinical Trials

18. Genetic determinants of penicillin tolerance in <i>Vibrio cholerae</i>. (PubMed)

Genetic determinants of penicillin tolerance in Vibrio cholerae. Many bacteria are resistant to killing (tolerant) by typically bactericidal antibiotics due to their ability to counteract drug-induced cell damage. Vibrio cholerae, the cholera agent, displays an unusually high tolerance to diverse inhibitors of cell wall synthesis. Exposure to these agents, which in other bacteria leads to lysis and death, results in a breakdown of the cell wall and subsequent sphere formation in V (...) . cholerae Spheres readily recover to rod-shaped cells upon antibiotic removal, but the mechanisms mediating the recovery process are not well characterized. Here, we found that the mechanisms of recovery are dependent on environmental conditions. Interestingly, on agarose pads, spheres undergo characteristic stages during the restoration of rod shape. Drug inhibition and microscopy experiments suggest that class A penicillin binding proteins (aPBPs) play a more active role than the Rod system

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2018 Antimicrobial Agents and Chemotherapy

19. Molecular Genetic, Host-derived and Clinical Determinants of Long-term Survival in Glioblastoma

or more studies before adding more. Molecular Genetic, Host-derived and Clinical Determinants of Long-term Survival in Glioblastoma The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT03770468 Recruitment Status : Recruiting (...) First Posted : December 10, 2018 Last Update Posted : December 12, 2018 See Sponsor: European Organisation for Research and Treatment of Cancer - EORTC Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC Study Details Study Description Go to Brief Summary: This pro - and retrospective multicenter clinical epidemiological study studies the molecular genetic, host-derived and clinical determinants of glioblastoma patients with an overall

2018 Clinical Trials

20. A GENETIC VARIANT IN THE BCL2 GENE ASSOCIATES WITH ADALIMUMAB RESPONSE IN HIDRADENITIS SUPPURATIVA CLINICAL TRIALS AND REGULATES EXPRESSION OF BCL2. (PubMed)

A GENETIC VARIANT IN THE BCL2 GENE ASSOCIATES WITH ADALIMUMAB RESPONSE IN HIDRADENITIS SUPPURATIVA CLINICAL TRIALS AND REGULATES EXPRESSION OF BCL2. Hidradenitis Suppurativa (HS) is a chronic skin disease with strong genetic component and prevalance from 0.5% to 4%. Adalimumab is the only treatment approved by either the European Medicines Agency (EMA) or the US Food or Drug Administration (FDA) for the management of moderate-to-severe HS. To identify genetic variants associated with adalimumab (...) response, we performed a genome-wide association study (GWAS) from the largest two Phase 3 HS clinical trials (PIONEER I and II) to date. Through direct genotyping and imputation, we tested almost 7 million genetic variants with MAF > 5% and identified one single linkage disequilibrium (LD) block, located in the intron of the BCL2 gene, which reached genome-wide significance (lead single-nucleotide polymorphism [SNP] rs 59532114; p=2.35E-08). Bioinformatic analysis and functional genomics experiments

2019 Journal of Investigative Dermatology

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