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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 27 Research Studies DisplayedWing SE, Hu H, Lopez L
Recall of genomic testing results among patients with cancer.
Genomic testing of somatic and germline DNA has transformed cancer care. However, low genetic knowledge among patients may compromise care and health outcomes. Given the rise in genomic testing, we sought to understand patients' knowledge of their genetic test results. The investigators conducted a survey-based study with 85 patients at a comprehensive cancer center and compared self-reported recall of (a) having had somatic/germline testing and (b) their specific somatic/germline results to the genomic test results documented in the medical record.
AHRQ-funded; HS024984.
Citation: Wing SE, Hu H, Lopez L .
Recall of genomic testing results among patients with cancer.
Oncologist 2021 Dec;26(12):e2302-e05. doi: 10.1002/onco.13928..
Keywords: Cancer, Genetics, Health Literacy
Golob JL, Rao K
Signal versus noise: how to analyze the microbiome and make progress on antimicrobial resistance.
This paper’s objective is to: 1) review the current thought on risk from antibiotic-resistant organization (ARO) acquisition; 2) review the current understanding on the gut microbiome’s ability to resist colonization with AROs; 3) describe how experimental model systems can test these global initial, global insights to arrive at more granular, mechanistic ones; and 4) suggest a path forward to make further progress in the field. This review is informed from experiences and successes with understanding of the role of the microbiome in mediating risk of Clostridioides difficile infection.
AHRQ-funded; HS027431.
Citation: Golob JL, Rao K .
Signal versus noise: how to analyze the microbiome and make progress on antimicrobial resistance.
J Infect Dis 2021 Jun 16;223(Suppl 3):S214-S21. doi: 10.1093/infdis/jiab184..
Keywords: Clostridium difficile Infections, Healthcare-Associated Infections (HAIs), Genetics
Arkhipova-Jenkins I, Helfand M, Armstrong C
Antibody response after SARS-CoV-2 infection and implications for immunity : a rapid living review.
This rapid literature review synthesizes evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether the antibodies confer natural immunity. Seven databases were searched from January 1 to December 15, 2020, limited to peer-reviewed publications in English. Two investigators extracted study data and rated quality. Moderate-strength evidence suggested that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and IgG levels peak approximately 25 days after symptom onset and can remain detectable for at least 120 days. Moderate-strength evidence suggested that IgM levels peak at approximately 20 days and then decline. There is low-strength evidence that most adults generate neutralizing antibodies. Reasons why some adults do not develop antibodies after SARS-CoV-2 are unclear.
AHRQ-funded; 290201700003C.
Citation: Arkhipova-Jenkins I, Helfand M, Armstrong C .
Antibody response after SARS-CoV-2 infection and implications for immunity : a rapid living review.
Ann Intern Med 2021 Jun;174(6):811-21. doi: 10.7326/m20-7547..
Keywords: COVID-19, Infectious Diseases, Genetics, Evidence-Based Practice
Staley BS, Milko LV, Waltz M
Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial.
Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report described the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey.
AHRQ-funded; HS000032.
Citation: Staley BS, Milko LV, Waltz M .
Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial.
Trials 2021 Jun 14;22(1):395. doi: 10.1186/s13063-021-05341-2..
Keywords: Children/Adolescents, Genetics, Ambulatory Care and Surgery
Asti L, Hopley C, Avelis C
The potential clinical and economic value of a human papillomavirus primary screening test that additionally identifies genotypes 31, 45, 51, and 52 individually.
This study looked at the potential clinical and economic value of a human papillomavirus (HPV) primary screening test that additionally identified genotypes 31,45,51, and 52 along with genotypes 16 and 18. The authors developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity. Currently HPV primary screening results in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping and later screening women with certain genotypes averted 903 to 3163 invasive procedures and results in 0 to 3 more ICC cases compared with current primary screening tests. Extended genotyping was cost effective when costing $75 and cost saving when costing $43. When the probabilities of disease progression increased 2-4 times, it was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life-years.
AHRQ-funded; HS023317.
Citation: Asti L, Hopley C, Avelis C .
The potential clinical and economic value of a human papillomavirus primary screening test that additionally identifies genotypes 31, 45, 51, and 52 individually.
Sex Transm Dis 2021 May;48(5):370-80. doi: 10.1097/olq.0000000000001327.
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Keywords: Sexual Health, Infectious Diseases, Screening, Diagnostic Safety and Quality, Genetics, Cancer: Cervical Cancer, Cancer, Women
Richardson JS, Kemper AR, Grosse SD
Health and economic outcomes of newborn screening for infantile-onset Pompe disease.
The authors sought to estimate health and economic outcomes associated with newborn screening for infantile-onset Pompe disease in the United States. They found that newborn screening for Pompe disease resulted in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.
AHRQ-funded; HS020644.
Citation: Richardson JS, Kemper AR, Grosse SD .
Health and economic outcomes of newborn screening for infantile-onset Pompe disease.
Genet Med 2021 Apr;23(4):758-66. doi: 10.1038/s41436-020-01038-0..
Keywords: Newborns/Infants, Screening, Genetics
Lusczek ER, Ingraham NE, Karam BS
Characterizing COVID-19 clinical phenotypes and associated comorbidities and complication profiles.
The purpose of this retrospective analysis of COVID-19 patients was to identify specific clinical phenotypes across COVID-19 patients and to compare admission characteristics and outcomes. Investigators identified three clinical COVID-19 phenotypes, reflecting patient populations with different comorbidities, complications, and clinical outcomes. They recommended future research to determine the utility of these phenotypes in clinical practice and trial design.
AHRQ-funded; HS026379.
Citation: Lusczek ER, Ingraham NE, Karam BS .
Characterizing COVID-19 clinical phenotypes and associated comorbidities and complication profiles.
PLoS One 2021 Mar 31;16(3):e0248956. doi: 10.1371/journal.pone.0248956..
Keywords: COVID-19, Genetics
Ruaño G, Tortora J, Robinson S
Subanalysis of the CYP-GUIDES trial: CYP2D6 functional stratification and operational timeline selection.
CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) was a Randomized Controlled Trial comparing 2 outcomes in hospitalized patients with major depressive disorder treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. In this paper, the authors described a subanalysis of the CYP-GUIDES trial. They concluded that there was an effect of pharmacogenetic clinical decision support that reduced length of stay in patients with CYP2D6 subfunctional status and reduced prescribing of CYP2D6 substrate dependent drugs.
AHRQ-funded; HS022304
Citation: Ruaño G, Tortora J, Robinson S .
Subanalysis of the CYP-GUIDES trial: CYP2D6 functional stratification and operational timeline selection.
Psychiatry Res 2021 Mar;297:113571. doi: 10.1016/j.psychres.2020.113571..
Keywords: Clinical Decision Support (CDS), Depression, Genetics, Medication, Behavioral Health
Hammad Mrig E
Integrating fundamental cause theory and Bourdieu to explain pathways between socioeconomic status and health: the case of health insurance denials for genetic testing.
This paper proposes that Pierre Bourdieu's theories of capital and symbolic power can be integrated with fundamental cause theory to address limitations in the latter theory, making it more useful in health disparities research. This work deepens appreciation for the durable relationship between socioeconomic status and health. Study results reveal the multiple and complex mechanisms that play a role in access to healthcare services, which has significant implications for how we think about the role of health policy in addressing health disparities.
AHRQ-funded; HS017589.
Citation: Hammad Mrig E .
Integrating fundamental cause theory and Bourdieu to explain pathways between socioeconomic status and health: the case of health insurance denials for genetic testing.
Sociol Health Illn 2021 Jan;43(1):133-48. doi: 10.1111/1467-9566.13195..
Keywords: Social Determinants of Health, Disparities, Health Insurance, Access to Care, Genetics, Policy
Fraiman YS, Wojcik MH
The influence of social determinants of health on the genetic diagnostic odyssey: who remains undiagnosed, why, and to what effect?
This review article synthesizes the available evidence regarding population disparities in genetic testing for pediatric rare disease diagnosis and identifies gaps in care. The influence of social determinants of health is known, but this study’s goal is to examine the prevalence and nature of disparities in diagnostic testing. It synthesizes the available evidence regarding disparities, defining the need for further, prospective studies.
AHRQ-funded; HS000063.
Citation: Fraiman YS, Wojcik MH .
The influence of social determinants of health on the genetic diagnostic odyssey: who remains undiagnosed, why, and to what effect?
Pediatr Res 2021 Jan;89(2):295-300. doi: 10.1038/s41390-020-01151-5..
Keywords: Children/Adolescents, Social Determinants of Health, Genetics, Diagnostic Safety and Quality, Screening, Disparities
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