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AHRQ Research Studies
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Research Studies is a compilation of published research articles funded by AHRQ or authored by AHRQ researchers.
Results
1 to 25 of 32 Research Studies DisplayedDinan MA, Wilson LE, Reed SD
Association of 21-gene assay (OncotypeDX) testing and receipt of chemotherapy in the Medicare breast cancer patient population following initial adoption.
This study looked at trends in the association of 21-gene assay testing and receipt of chemotherapy in the Medicare breast cancer patient population following initial adoption from 2001 to 2011. The investigators looked at updated SEER-Medicare data from 2004 and 2011. The cohort included 26,009 patients who met inclusion criteria. Assay use was associated with a decrease in absolute percentage use of chemotherapy by 4.5%, which became even more pronounced from 2008-2011 with a decrease of 6.8%.
AHRQ-funded; HS022189.
Citation: Dinan MA, Wilson LE, Reed SD .
Association of 21-gene assay (OncotypeDX) testing and receipt of chemotherapy in the Medicare breast cancer patient population following initial adoption.
Clin Breast Cancer 2020 Dec;20(6):487-94.e1. doi: 10.1016/j.clbc.2020.05.010..
Keywords: Cancer: Breast Cancer, Cancer, Treatments, Genetics, Medicare, Women, Healthcare Utilization
Chen Y, Liang KY, Tong P
A pseudolikelihood approach for assessing genetic association in case-control studies with unmeasured population structure.
In this paper, researchers propose a novel statistical method to estimate the association between genetic markers and diseases in case-control studies with unmeasured population substructure. The performance of the proposed method, relative to the existing methods, on bias, coverage probability, and computational time, is assessed through simulations. The method is applied to an end-stage renal disease study in African Americans population.
AHRQ-funded; HS022900.
Citation: Chen Y, Liang KY, Tong P .
A pseudolikelihood approach for assessing genetic association in case-control studies with unmeasured population structure.
Stat Methods Med Res 2020 Nov;29(11):3153-65. doi: 10.1177/0962280220921212..
Keywords: Genetics, Research Methodologies
Griesemer I, Staley BS, Lightfoot AF
Engaging community stakeholders in research on best practices for clinical genomic sequencing.
This paper describes the NCGENES2 study which explored the impact of engagement between clinicians and caregivers of children with undiagnosed conditions in the context of a diagnostic genomic sequencing study. A Community Consult Team (CCT) was formed with diverse parents and advocates for children with genetic and/or neurodevelopmental conditions. Early and consistent engagement with the CCT resulted in adaptations to study protocols relevant to this unique study population.
AHRQ-funded; HS000032.
Citation: Griesemer I, Staley BS, Lightfoot AF .
Engaging community stakeholders in research on best practices for clinical genomic sequencing.
Per Med 2020 Nov;16(6):435-44. doi: 10.2217/pme-2020-0074..
Keywords: Children/Adolescents, Patient and Family Engagement, Genetics
Knerr S, West KM, Angelo FA
Organizational readiness to implement population-based screening and genetic service delivery for hereditary cancer prevention and control.
Programs conducting population-based screening and genetic service delivery for hereditary cancer prevention and control are rare in practice. The authors interviewed individuals instrumental in implementing seven unique clinical programs conducting either universal tumor screening for Lynch Syndrome or routine family history screening and provision of genetic services for hereditary breast and ovarian cancer in the United States. Their findings suggest that developing interventions targeting change efficacy and cultivating practice change champions may be two promising ways to increase uptake of population-based hereditary cancer screening and genetic service delivery in clinical practice.
AHRQ-funded; HS022982.
Citation: Knerr S, West KM, Angelo FA .
Organizational readiness to implement population-based screening and genetic service delivery for hereditary cancer prevention and control.
J Genet Couns 2020 Oct;29(5):867-76. doi: 10.1002/jgc4.1216.
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Keywords: Cancer, Screening, Genetics, Prevention, Guidelines, Healthcare Delivery, Organizational Change, Implementation
Feldman AG, Parsons JA, Dutmer CM
Subacute liver failure following gene replacement therapy for spinal muscular atrophy type 1.
This paper reports on two cases of transient, drug-induced liver failure after gene replacement therapy using an adeno-associated virus vector containing the survival motor neuron 1 gene.
AHRQ-funded; HS026510.
Citation: Feldman AG, Parsons JA, Dutmer CM .
Subacute liver failure following gene replacement therapy for spinal muscular atrophy type 1.
J Pediatr 2020 Oct;225:252-58.e1. doi: 10.1016/j.jpeds.2020.05.044..
Keywords: Newborns/Infants, Neurological Disorders, Genetics, Treatments, Adverse Drug Events (ADE), Adverse Events, Medication, Medication: Safety, Patient Safety, Case Study
Edwards RL, Heueck I, Lee SG
Potent, specific MEPicides for treatment of zoonotic staphylococci.
In this study, researchers demonstrated that fosmidomycin (FSM) inhibited the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. They synthesized a series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM, and their data indicated that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci but also bypassed the need for GlpT-mediated cellular transport. They concluded that their data indicated that the prodrug MEPicides selectively and robustly inhibited DXR in zoonotic staphylococci, and, further, that DXR represented a promising, druggable target for future development.
AHRQ-funded; HS021736; HS024269.
Citation: Edwards RL, Heueck I, Lee SG .
Potent, specific MEPicides for treatment of zoonotic staphylococci.
PLoS Pathog 2020 Jun;16(6):e1007806. doi: 10.1371/journal.ppat.1007806..
Keywords: Infectious Diseases, Antibiotics, Medication, Genetics
Johnson A, Broughton S, Aponte-Soto L
Participatory genomic testing can effectively disseminate cardiovascular pharmacogenomics concepts within federally qualified health centers: a feasibility study.
Researchers assessed feasibility of an educational program designed to enhance stakeholder knowledge and perceptions of pharmacogenomics at a federally qualified health center. Twenty providers and 10 community members were recruited for a feasibility study via convenience sampling. The researchers determined that a pharmacogenomics educational program tailored for an underrepresented community was feasible and acceptable; outcomes will advise methodology for larger implementation studies.
AHRQ-funded; HS019461.
Citation: Johnson A, Broughton S, Aponte-Soto L .
Participatory genomic testing can effectively disseminate cardiovascular pharmacogenomics concepts within federally qualified health centers: a feasibility study.
Ethn Dis 2020 Apr;30(Suppl 1):167-76. doi: 10.18865/ed.30.S1.167..
Keywords: Genetics, Cardiovascular Conditions, Community Partnerships, Health Literacy, Education: Patient and Caregiver
Mills J, Fakolade A
AHRQ Author: Mills J
Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer.
In this case study, a 31-year-old woman presents for a well-woman examination. She indicates that her mother was diagnosed with tubal cancer at age 40, that her 42-year-old sister was recently diagnosed with breast cancer, and that her maternal aunt was diagnosed with breast cancer at age 45.
AHRQ-authored.
Citation: Mills J, Fakolade A .
Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer.
Am Fam Physician 2020 Feb 15;101(4):239-40..
Keywords: U.S. Preventive Services Task Force (USPSTF), Cancer: Breast Cancer, Cancer, Genetics, Screening, Women, Prevention, Case Study
Ruaño Ruaño, Robinson S, Holford T
Results of the CYP-GUIDES randomized controlled trial: total cohort and primary endpoints.
CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) was a randomized controlled trial (RCT) comparing 2 outcomes in hospitalized patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. This paper describes the results of that study. The primary outcome was hospital Length of Stay (LOS) and the secondary outcome was the Re-Admission Rate (RAR) 30 days after discharge.
AHRQ-funded; HS022304.
Citation: Ruaño Ruaño, Robinson S, Holford T .
Results of the CYP-GUIDES randomized controlled trial: total cohort and primary endpoints.
Contemp Clin Trials 2020 Feb;89:105910. doi: 10.1016/j.cct.2019.105910..
Keywords: Depression, Behavioral Health, Genetics, Medication
Liu Y, Chen Y, Scheet P
A meta-analytic framework for detection of genetic interactions.
The researchers propose a new procedure for detecting gene-by-gene interactions through heterogeneity in estimated low-order (e.g., marginal) effect sizes by leveraging population structure, or ancestral differences, among studies in which the same phenotypes were measured. They implement this approach in a meta-analytic framework, which offers numerous advantages, such as robustness and computational efficiency, and is necessary when data-sharing limitations restrict joint analysis.
AHRQ-funded; HS022900.
Citation: Liu Y, Chen Y, Scheet P .
A meta-analytic framework for detection of genetic interactions.
Genet Epidemiol 2016 Nov;40(7):534-43. doi: 10.1002/gepi.21996.
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Keywords: Genetics, Research Methodologies, Health Information Technology (HIT)
Biermacka JM, Chung SJ, Amasu SM
Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease.
The researchers performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease (PD). They concluded that although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk.
AHRQ-funded; HS024057.
Citation: Biermacka JM, Chung SJ, Amasu SM .
Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease.
Parkinsonism Relat Disord 2016 Nov;32:25-30. doi: 10.1016/j.parkreldis.2016.08.002.
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Keywords: Genetics, Risk, Neurological Disorders
Chuang LS, Villaverde N, Hui KY
A frameshift in CSF2RB predominant among Ashkenazi Jews increases risk for Crohn's disease and reduces monocyte signaling via GM-CSF.
The authors sought to identify rare, Crohn's disease-associated frameshift variants of high functional and statistical effects. They associated Crohn's disease with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor.
AHRQ-funded; HS021747.
Citation: Chuang LS, Villaverde N, Hui KY .
A frameshift in CSF2RB predominant among Ashkenazi Jews increases risk for Crohn's disease and reduces monocyte signaling via GM-CSF.
Gastroenterology 2016 Oct;151(4):710-23.e2. doi: 10.1053/j.gastro.2016.06.045.
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Keywords: Digestive Disease and Health, Genetics, Risk, Racial and Ethnic Minorities
Li D, Achkar JP, Haritunians T
A pleiotropic missense variant in SLC39A8 is associated with crohn's disease and human gut microbiome composition.
This study aimed to identify novel associations between inflammatory bowel disease (IBD) and functional genetic variants. The results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including Crohn's disease.
AHRQ-funded; HS021747.
Citation: Li D, Achkar JP, Haritunians T .
A pleiotropic missense variant in SLC39A8 is associated with crohn's disease and human gut microbiome composition.
Gastroenterology 2016 Oct;151(4):724-32. doi: 10.1053/j.gastro.2016.06.051.
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Keywords: Digestive Disease and Health, Genetics, Risk
Carmody D, Naylor RN, Bell CD
GCK-MODY in the US National Monogenic Diabetes Registry: frequently misdiagnosed and unnecessarily treated.
GCK-MODY (diabetes caused by mutations in the glucokinase (GCK) gene) leads to mildly elevated blood glucose typically not requiring therapy. It has been described in all ethnicities, but mainly in Caucasian Europeans. The researchers describe our US cohort of GCK-MODY. Their data show that a high detection rate of GCK-MODY is possible based on clinical phenotype and that prior to genetic diagnosis, a large percentage are inappropriately treated with glucose-lowering therapies.
AHRQ-funded; HS023007.
Citation: Carmody D, Naylor RN, Bell CD .
GCK-MODY in the US National Monogenic Diabetes Registry: frequently misdiagnosed and unnecessarily treated.
Acta Diabetol 2016 Oct;53(5):703-8. doi: 10.1007/s00592-016-0859-8.
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Keywords: Diabetes, Registries, Diagnostic Safety and Quality, Genetics
Kopylov U, Boucher G, Waterman M
Genetic predictors of benign course of ulcerative colitis - a North American inflammatory bowel disease genetics consortium study.
The aim of this project was to identify the genetic predictors of benign ulcerative colitis (UC) phenotype. No single-nucleotide polymorphisms from inflammatory bowel disease susceptibility loci were found to be associated with a benign UC disease course. These findings suggested on the exploratory analysis merit extension to larger discovery cohorts.
AHRQ-funded; HS021747.
Citation: Kopylov U, Boucher G, Waterman M .
Genetic predictors of benign course of ulcerative colitis - a North American inflammatory bowel disease genetics consortium study.
Inflamm Bowel Dis 2016 Oct;22(10):2311-6. doi: 10.1097/mib.0000000000000913.
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Keywords: Diabetes, Diagnostic Safety and Quality, Genetics
Cutting E, Banchero M, Beitelshees AL
User-centered design of multi-gene sequencing panel reports for clinicians.
The objective of this study was to develop a high-fidelity prototype for delivering multi-gene sequencing panel (GS) reports to clinicians that simulates the user experience of a final application. Findings illustrated a need to support customized notification approaches, user-specific information, and access to genetics specialists with GS reports. These design principles can be incorporated into software applications that deliver GS reports.
AHRQ-funded; R21 HS023390.
Citation: Cutting E, Banchero M, Beitelshees AL .
User-centered design of multi-gene sequencing panel reports for clinicians.
J Biomed Inform 2016 Oct;63:1-10. doi: 10.1016/j.jbi.2016.07.014.
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Keywords: Genetics, Health Information Technology (HIT), Healthcare Delivery
Guerrerio AL, Frischmeyer-Guerrerio PA, Huang C
Increased prevalence of inflammatory bowel disease in patients with mutations in genes encoding the receptor subunits for TGFbeta.
The researchers evaluated the potential genetic risk factors that could predict which patients with Loeys-Dietz syndrome (LDS) would develop inflammatory bowel disease (IBD). They reported a 10-fold increase in the prevalence of IBD in patients with LDS compared with the general population.
AHRQ-funded; HS021747.
Citation: Guerrerio AL, Frischmeyer-Guerrerio PA, Huang C .
Increased prevalence of inflammatory bowel disease in patients with mutations in genes encoding the receptor subunits for TGFbeta.
Inflamm Bowel Dis 2016 Sep;22(9):2058-62. doi: 10.1097/mib.0000000000000872.
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Keywords: Digestive Disease and Health, Genetics, Risk
Sieberts SK, Zhu F, Garcia-Garcia J
Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis.
A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of an open challenge framework which enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies.
AHRQ-funded; HS018517.
Citation: Sieberts SK, Zhu F, Garcia-Garcia J .
Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis.
Nat Commun 2016 Aug 23;7:12460. doi: 10.1038/ncomms12460..
Keywords: Genetics, Arthritis
Richesson RL, Sun J, Pathak J
Clinical phenotyping in selected national networks: demonstrating the need for high-throughput, portable, and computational methods.
The authors sought to use electronic health records data to advance understanding of disease risk and drug response, and to support the practice of precision medicine on a national scale. They found that machine learning approaches that generate phenotype definitions from patient features and clinical profiles will result in truly computational phenotypes, as it comes from data rather than experts. They suggested that research networks and phenotype developers cooperate to develop methods, collaboration platforms, and data standards that will enable computational phenotyping and modernize biomedical research.
AHRQ-funded; HS023921; HS023077.
Citation: Richesson RL, Sun J, Pathak J .
Clinical phenotyping in selected national networks: demonstrating the need for high-throughput, portable, and computational methods.
Artif Intell Med 2016 Jul;71:57-61. doi: 10.1016/j.artmed.2016.05.005.
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Keywords: Data, Electronic Health Records (EHRs), Genetics, Patient-Centered Healthcare
Roberts MC, Bryson A, Weinberger M
Patient-centered communication for discussing oncotype DX testing.
The researchers identified patient-centered communication strategies/gaps for discussing Oncotype DX testing (ODX) results. They applied a patient-centered communication framework to analyze qualitative interviews with oncologists about how they communicate about ODX with patients. Overall, providers discussed four patient-centered communication domains: exchanging information, assessing uncertainty, making decisions and cross-cutting themes.
AHRQ-funded; HS019468; HS022189.
Citation: Roberts MC, Bryson A, Weinberger M .
Patient-centered communication for discussing oncotype DX testing.
Cancer Invest 2016 May 27;34(5):205-12. doi: 10.3109/07357907.2016.1172637.
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Keywords: Cancer, Cancer: Breast Cancer, Communication, Clinician-Patient Communication, Shared Decision Making, Genetics, Patient and Family Engagement, Patient-Centered Healthcare, Women
Williams RC, Elston RC, Kumar P
Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).
The researchers studied individual genetic ancestry (IGA) in four samples in the Family Investigation of Nephropathy and Diabetes (FIND). They found that the identified set of ancestry informtive markers (AIMs) may be particularly useful for estimating genetic admixture in populations from the Americas. They concluded that odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.
AHRQ-funded; HS008365.
Citation: Williams RC, Elston RC, Kumar P .
Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).
BMC Genomics 2016 May 4;17:325. doi: 10.1186/s12864-016-2654-x.
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Keywords: Diabetes, Family Health and History, Genetics, Neurological Disorders, Racial and Ethnic Minorities
Mathur MB, Epel E, Kind S
Perceived stress and telomere length: a systematic review, meta-analysis, and methodologic considerations for advancing the field.
The researchers conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL). They found that increased PS was associated with a very small decrease in TL and that this relationship was similar between sexes. They concluded that the association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. The authors recommended that futre research assess for potential confounders and use longitudinal, multidimensional models of stress.
AHRQ-funded; HS019816.
Citation: Mathur MB, Epel E, Kind S .
Perceived stress and telomere length: a systematic review, meta-analysis, and methodologic considerations for advancing the field.
Brain Behav Immun 2016 May;54:158-69. doi: 10.1016/j.bbi.2016.02.002.
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Keywords: Evidence-Based Practice, Genetics, Stress
Ali M, Yopp A, Gopal P
A variant in PNPLA3 associated with fibrosis progression but not hepatocellular carcinoma in patients with hepatitis C virus infection.
This study evaluated the association between single nucleotide polymorphism (SNP) in PNPLA3 and fibrosis progression and development of hepatocellular carcinoma (HCC) among HCV-infected patients. The authors performed a secondary analysis of data from participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. They concluded that, based on data from the HALT-C trial, the PNPLA3 CG/GG SNP at rs738409 is associated with fibrosis progression but not development of HCC in patients with HCV infection.
AHRQ-funded; HS022418.
Citation: Ali M, Yopp A, Gopal P .
A variant in PNPLA3 associated with fibrosis progression but not hepatocellular carcinoma in patients with hepatitis C virus infection.
Clin Gastroenterol Hepatol 2016 Feb;14(2):295-300. doi: 10.1016/j.cgh.2015.08.018.
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Keywords: Cancer, Hepatitis, Genetics
Reynolds RJ, Vazquez AI, Srinivasasainagendra V
Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.
The researchers hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. They measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. They demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease.
AHRQ-funded; HS021110.
Citation: Reynolds RJ, Vazquez AI, Srinivasasainagendra V .
Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.
Rheumatol Int 2016 Feb;36(2):263-70. doi: 10.1007/s00296-015-3364-4.
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Keywords: Centers for Education and Research on Therapeutics (CERTs), Evidence-Based Practice, Genetics, Risk, Obesity
Cleynen I, Boucher G, Jostins L
Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.
The researchers undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between between Crohn's disease and ulcerative colitis. Their data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined.
AHRQ-funded; HS021747.
Citation: Cleynen I, Boucher G, Jostins L .
Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.
Lancet 2016 Jan 9;387(10014):156-67. doi: 10.1016/s0140-6736(15)00465-1.
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Keywords: Genetics, Digestive Disease and Health, Chronic Conditions