Publications by authors named "Kathleen Palmer"

8 Publications

  • Page 1 of 1

and Long QT Syndrome in 1/45 Amish: The Road From Identification to Implementation of Culturally Appropriate Precision Medicine.

Circ Genom Precis Med 2020 12 3;13(6):e003133. Epub 2020 Nov 3.

Regeneron Genetics Center LLC, Tarrytown, NY (C.V.H., N.G., C.G.-J., A.E., A.R.S.).

Background: In population-based research exome sequencing, the path from variant discovery to return of results is not well established. Variants discovered by research exome sequencing have the potential to improve population health.

Methods: Population-based exome sequencing and agnostic ExWAS were performed 5521 Amish individuals. Additional phenotyping and in vitro studies enabled reclassification of a variant from variant of unknown significance to pathogenic. Results were returned to participants in a community setting.

Results: A missense variant was identified in (c.671C>T, p.T224M), a gene associated with long QT syndrome type 1, which can cause syncope and sudden cardiac death. The p.T224M variant, present in 1/45 Amish individuals is rare in the general population (1/248 566 in gnomAD) and was highly associated with QTc on electro-cardiogram (=5.53E-24, β=20.2 ms/allele). Because of the potential importance of this variant to the health of the population, additional phenotyping was performed in 88 p.T224M carriers and 54 noncarriers. There was stronger clinical evidence of long QT syndrome in carriers (38.6% versus 5.5%, =0.0006), greater history of syncope (32% versus 17%, =0.020), and higher rate of sudden cardiac death in first degree relatives
Conclusions: This work provides a framework by which research exome sequencing can be rapidly translated in a culturally appropriate manner to directly benefit research participants and enable population precision health.
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http://dx.doi.org/10.1161/CIRCGEN.120.003133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748050PMC
December 2020

Ethical and Safety Concerns Regarding the Use of Mental Health-Related Apps in Counseling: Considerations for Counselors.

J Technol Behav Sci 2020 Aug 31:1-14. Epub 2020 Aug 31.

University of Detroit Mercy, 4001 W. McNichols Road, Detroit, MI 48221-3038 USA.

Mental health-related smartphone apps (MHapps) have the potential to greatly enhance and enrich the counseling relationship, and dramatically improve the lives of clients. However, a large portion of MHapps have not been empirically researched and found to be effective. An average of 2 million apps are available in the Apple and Android stores, and users average more than 80 apps on their phones. Many of the apps lack disclaimers about the collection of user information, and there is no governing body to oversee and regulate app development and availability. This is particularly problematic with mental health-related smartphone apps, because many developers are not affiliated with mental health professionals, and many apps do not provide emergency information should a mental health emergency occur while using the app. Moreover, users are left to haphazardly make decisions about health-related apps usage without assistance. Counselors who supplement counseling with mental health-related smartphone apps could unknowingly violate their Code of Ethics by integrating apps that may jeopardize their clients' safety. The authors review literature related to mental health-related app efficacy, safety, and ethics and provide a compilation of items to consider that can be used before supplementing counseling with mental health-related apps.
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http://dx.doi.org/10.1007/s41347-020-00160-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457894PMC
August 2020

Delineation of Novel Compound Heterozygous Variants in LTBP2 Associated with Juvenile Open Angle Glaucoma.

Genes (Basel) 2018 Oct 30;9(11). Epub 2018 Oct 30.

Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C>G, p.(Pro989Arg); c.5235T>G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 () segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles.
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http://dx.doi.org/10.3390/genes9110527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266624PMC
October 2018

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2018 01 1;11(2):181-191. Epub 2017 Nov 1.

Department of Medicine, University of Maryland, Baltimore, Maryland.

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).

Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.

Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.

Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).

Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
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http://dx.doi.org/10.1016/j.jcin.2017.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775044PMC
January 2018

Prioritizing Approaches to Engage Community Members and Build Trust in Biobanks: A Survey of Attitudes and Opinions of Adults within Outpatient Practices at the University of Maryland.

J Pers Med 2015 Jul 28;5(3):264-79. Epub 2015 Jul 28.

Program in Personalized & Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Background: Achieving high participation of communities representative of all sub-populations is needed in order to ensure broad applicability of biobank study findings. This study aimed to understand potentially mutable attitudes and opinions commonly correlated with biobank participation in order to inform approaches to promote participation in biobanks.

Methods: Adults from two University of Maryland (UMD) Faculty Physicians, Inc. outpatient practices were invited to watch a video and complete a survey about a new biobank initiative. We used: Chi-square to assess the relationship between willingness to join the biobank and participant characteristics, other potentially mutable attitudes and opinions, and trust in the UMD. We also used t-test to assess the relationship with trust in medical research. We also prioritize proposed actions to improve attitudes and opinions about joining biobanks according to perceived responsiveness.

Results: 169 participants completed the study, 51% of whom indicated a willingness to join the biobank. Willingness to join the biobank was not associated with age, gender, race, or education but was associated with respondent comfort sharing samples and clinical information, concerns related to confidentiality, potential for misuse of information, trust in UMD, and perceived health benefit. In ranked order, potential actions we surveyed that might alleviate some of these concerns include: increase chances to learn more about the biobank, increase opportunities to be updated, striving to put community concerns first, including involving community members as leaders of biobank research, and involving community members in decision making.

Conclusions: This study identified several attitudes and opinions that influence decisions to join a biobank, including many concerns that could potentially be addressed by engaging community members. We also demonstrate our method of prioritizing ways to improve attitudes and opinions about joining a biobank according to perceived responsiveness.
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http://dx.doi.org/10.3390/jpm5030264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600147PMC
July 2015

Implementation of pharmacogenetics: the University of Maryland Personalized Anti-platelet Pharmacogenetics Program.

Am J Med Genet C Semin Med Genet 2014 Mar 10;166C(1):76-84. Epub 2014 Mar 10.

Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients' are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within 5 hr along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine.
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http://dx.doi.org/10.1002/ajmg.c.31396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066997PMC
March 2014

Safety and immunogenicity of a recombinant multivalent group a streptococcal vaccine in healthy adults: phase 1 trial.

JAMA 2004 Aug;292(6):709-15

Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA.

Context: Group A streptococcal infections and their sequelae represent a global health problem. Recent advances have allowed previous obstacles associated with group A streptococcal vaccine development to be overcome.

Objective: To preliminarily evaluate the safety and immunogenicity of ascending doses of a recombinant fusion peptide group A streptococcal vaccine containing N-terminal M protein fragments from serotypes 1, 3, 5, 6, 19, and 24 in healthy volunteers.

Design, Setting, And Participants: An open-label, uncontrolled, dose-ascending phase 1 vaccine trial of 28 healthy adult volunteers aged 18 to 50 years recruited from the metropolitan area of Baltimore, Md, between October 5, 1999, and February 26, 2003, using newspaper advertisements and posted fliers, and evaluated in the outpatient facility of the Center for Vaccine Development.

Interventions: Each volunteer received 3 spaced intramuscular injections of 50 microg (n = 8), 100 micro g (n = 10), or 200 microg (n = 10) of hexavalent group A streptococcal vaccine formulated with aluminum hydroxide into the deltoid muscle of alternating arms.

Main Outcome Measures: Assessments of clinical safety, including elicitation of antibodies that cross-react with host tissues, and immunogenicity as measured by enzyme-linked immunosorbent assay (ELISA) and assays of opsonophagocytic- and bactericidal-antibody responses.

Results: One year of intensive follow-up revealed the vaccine to be well tolerated. There was no evidence of tissue cross-reactive antibodies or immunological complications. At the highest (200 microg) dose, vaccination elicited significant increases in geometric mean antibody levels to all 6 component M antigens by ELISA (all P<.01) and to 5 of 6 M types in the opsonophagocytosis assay (all P<.05). In addition, postvaccination increases in serum bactericidal activity of at least 30% were observed in 31 (55%) of 56 assays.

Conclusion: These results provide the first evidence in humans that a hybrid fusion protein is a feasible strategy for evoking type-specific opsonic antibodies against multiple serotypes of group A streptococcus without eliciting antibodies that cross-react with host tissues, which represents a critical step in the development of a vaccine.
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http://dx.doi.org/10.1001/jama.292.6.709DOI Listing
August 2004
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