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Topics
- Adverse Drug Events (ADE) (1)
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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 15 of 15 Research Studies DisplayedZhang K, Potter RF, Marino J
Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus.
The study explored resistance patterns in Staphylococcus saprophyticus, a common cause of UTIs in women. Genomic analysis linked antibiotic resistance genes to susceptibility, identifying associations with SCCmec configurations and phage elements. This database aids in resistance surveillance for precise diagnosis and treatment, potentially curbing resistance transmission.
AHRQ-funded; HS027621.
Citation: Zhang K, Potter RF, Marino J .
Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus.
mSystems 2023 Dec 21; 8(6):e0069723. doi: 10.1128/msystems.00697-23..
Keywords: Genetics, Antibiotics, Urinary Tract Infection (UTI), Medication
McNeil JC, Sommer LM, Vallejo JG
Reduced ceftaroline susceptibility among invasive mrsa infections in children: a clinical and genomic investigation.
The purpose of this study was to assess the frequency of reduced susceptibility (RS) to ceftaroline among pediatric methicillin-resistant Staphylococcus aureus (MRSA) infections. The researchers evaluated MRSA isolates at a tertiary children's hospital for ceftaroline RS. Ceftaroline RS occurred only among health care associated infections in 2.9% of isolates, and were more often clindamycin-resistant.
AHRQ-funded; HS026896.
Citation: McNeil JC, Sommer LM, Vallejo JG .
Reduced ceftaroline susceptibility among invasive mrsa infections in children: a clinical and genomic investigation.
Antimicrob Agents Chemother 2022 Oct 18;66(10):e0074522. doi: 10.1128/aac.00745-22..
Keywords: Children/Adolescents, Medication, Methicillin-Resistant Staphylococcus aureus (MRSA), Infectious Diseases, Genetics
Tuteja S, Salloum RG, Elchynski AL
Multisite evaluation of institutional processes and implementation determinants for pharmacogenetic testing to guide antidepressant therapy.
This paper looked at how sites implement or plan implementation of pharmacogenetic (PGx) testing to guide antidepressant therapy. The authors administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. The first survey (Survey 1) collected data on the process and logistics of testing, and the second survey (Survey 2) asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best-worst scaling choice experiments. Four of the sites were still in the planning stage, 13 offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatrists (92%) and primary care (69%) providers. Justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional and commercial laboratories were used for testing. Sites were consistent in ranking Consolidated Framework for Implementation Research (CFIR) constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Key drivers for implementation were similar across sites and may help guide other institutions interested in providing PGx-guided pharmacotherapy for antidepressant management.
AHRQ-funded; HS026379.
Citation: Tuteja S, Salloum RG, Elchynski AL .
Multisite evaluation of institutional processes and implementation determinants for pharmacogenetic testing to guide antidepressant therapy.
Clin Transl Sci 2022 Feb; 15(2):371-83. doi: 10.1111/cts.13154..
Keywords: Medication, Depression, Behavioral Health, 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
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
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
Roberts MC, Bryson A, Weinberger M
Oncologists' barriers and facilitators for oncotype DX use: qualitative study.
The purpose of this paper was to understand better the U.S. oncologists' oncotype DX (ODX) uptake and how they use ODX during adjuvant chemotherapy decision making. This study identified multi-level factors that influence ODX uptake, including organizational factors, interpersonal factors, and intrapersonal factors.
AHRQ-funded; HS022189.
Citation: Roberts MC, Bryson A, Weinberger M .
Oncologists' barriers and facilitators for oncotype DX use: qualitative study.
Int J Technol Assess Health Care 2016 Jan;32(5):355-61. doi: 10.1017/s026646231600060x.
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Keywords: Cancer: Breast Cancer, Treatments, Decision Making, Genetics, Medication
Cutting EM, Overby CL, Banchero M
Using workflow modeling to identify areas to improve genetic test processes in the University of Maryland Translational Pharmacogenomics Project.
The researchers used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. They proposed a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center. They found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. They demonstrated theiruse of BPMN to improve this important clinical process for CYP2C19 genetic testing.
AHRQ-funded; HS023390.
Citation: Cutting EM, Overby CL, Banchero M .
Using workflow modeling to identify areas to improve genetic test processes in the University of Maryland Translational Pharmacogenomics Project.
AMIA Annu Symp Proc 2015 Nov 5;2015:466-74.
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Keywords: Genetics, Diagnostic Safety and Quality, Medication, Workflow, Quality Improvement, Quality of Care, Organizational Change
Duconge J, Cadilla CL, Seip RL
Why admixture matters in genetically-guided therapy: missed targets in the COAG and EU-PACT trials.
It is now well recognized that these commonly used pharmacogenetic algorithms perform poorly when applied to people with substantial African heritage. The authors of this letter conclude that the best approach for global pharmacogenetics is to guide warfarin dosing by using a pharmacogenetic-based algorithm that also accounts for the effect of admixture or ancestry proportions.
AHRQ-funded; HS022304.
Citation: Duconge J, Cadilla CL, Seip RL .
Why admixture matters in genetically-guided therapy: missed targets in the COAG and EU-PACT trials.
P R Health Sci J 2015 Sep;34(3):175-7..
Keywords: Racial and Ethnic Minorities, Genetics, Blood Thinners, Medication
Carmody D, Lindauer KL, Naylor RN
Adolescent non-adherence reveals a genetic cause for diabetes.
Glucokinase related maturity-onset diabetes of the young (GCK-MODY) is frequently unrecognized or misdiagnosed as Type 1 or Type 2 diabetes, resulting in unnecessary pharmacologic therapy. The authors recommend considering a genetic cause when evaluating every person with new-onset hyperglycaemia or those with atypical diabetes. Testing costs for the most common MODY causing genes may be offset by savings made in therapeutic costs. They suggest that it is important that all clinicians supervising diabetes care recognize the cardinal features that distinguish GCK-MODY from other forms of diabetes.
AHRQ-funded; HS023007.
Citation: Carmody D, Lindauer KL, Naylor RN .
Adolescent non-adherence reveals a genetic cause for diabetes.
Diabet Med 2015 Jun;32(6):e20-3. doi: 10.1111/dme.12669.
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Keywords: Children/Adolescents, Diabetes, Diagnostic Safety and Quality, Genetics, Medication
Samwald M, Minarro Gimenez JA, Boyce RD
Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies.
The authors developed Web Ontology Language (OWL) ontologies and automated reasoning methodologies to meet various goals such as providing a simple and concise formalism for representing pharmacogenomic knowledge. Their ontology-based framework can be used to represent, organize and reason over the growing wealth of pharmacogenomic knowledge, as well as to identify errors, inconsistencies and insufficient definitions in source data sets or individual patient data.
AHRQ-funded; HS019461.
Citation: Samwald M, Minarro Gimenez JA, Boyce RD .
Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies.
BMC Med Inform Decis Mak 2015 Feb 22;15:12. doi: 10.1186/s12911-015-0130-1..
Keywords: Comparative Effectiveness, Health Information Technology (HIT), Decision Making, Medication, Genetics
Yang SK, Hong M, Baek J
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.
The researchers identified and replicated a variant associated with substantially elevated risk of thiopurine-associated leukopenia diverse populations. Their approach identified a nonsynonymous and potentially damaging polymorphism in a gene involved in purine metabolism that demonstrated clinical usefulness for patients at risk of this potentially life-threatening condition.
AHRQ-funded; HS021747
Citation: Yang SK, Hong M, Baek J .
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.
Nat Genet. 2014 Sep;46(9):1017-20. doi: 10.1038/ng.3060..
Keywords: Genetics, Medication, Racial and Ethnic Minorities
Jonas DE, Amick HR, Feltner C
Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis.
This review assessed whether response to medications for alcohol use disorders varies by genotype. It found that estimates of effect for return to heavy drinking suggest it is possible that patients with at least one G allele of A118G polymorphism of OPRM1 might be more likely to respond to naltrexone.
290201200008I; 29032002T
Citation: Jonas DE, Amick HR, Feltner C .
Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis.
Pharmacogenomics 2014 Sep;15(13):1687-700. doi: 10.2217/pgs.14.121..
Keywords: Medication, Alcohol Use, Substance Abuse, Genetics
Jonas DE, Amick HR, Feltner C
Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis.
This review assessed whether response to medications for alcohol use disorders varies by genotype. It found that estimates of effect for return to heavy drinking suggest it is possible that patients with at least one G allele of A118G polymorphism of OPRM1 might be more likely to respond to naltrexone.
290201200008I; 29032002T
Citation: Jonas DE, Amick HR, Feltner C .
Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis.
Pharmacogenomics 2014 Sep;15(13):1687-700. doi: 10.2217/pgs.14.121..
Keywords: Medication, Alcohol Use, Substance Abuse, Genetics