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Article ; Online: Antibiotic Prophylaxis for Infective Endocarditis.

Peterson, Gail E / Crowley, Anna Lisa

2019 Volume 140, Issue 3, Page(s) 181–183

MeSH term(s)	American Heart Association ; Antibiotic Prophylaxis ; Endocarditis ; Endocarditis, Bacterial ; Hospitalization ; Humans
Language	English
Publishing date	2019-07-15
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.119.041085
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Article ; Online: Increasing the meaningful involvement of women in HIV cure-related research: a qualitative interview study in the United States.

HIV research & clinical practice

2024 Volume 24, Issue 1, Page(s) 2246717

Abstract: ... and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and ... procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women ...

Abstract	Background: Cisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery. Objective: We aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research. Materials and methods: We conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data. Results: We recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality. Conclusions: Our empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.
MeSH term(s)	Female ; Humans ; Male ; United States/epidemiology ; Qualitative Research ; Empirical Research ; Academies and Institutes ; Biopsy ; HIV Infections/drug therapy ; HIV Infections/epidemiology
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2578-7470
ISSN (online)	2578-7470
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Article ; Online: Maternal nutrient restriction and over-feeding during gestation alter expression of key factors involved in placental development and vascularization.

Reed, Sarah A / Ashley, Ryan / Silver, Gail / Splaine, Caitlyn / Jones, Amanda K / Pillai, Sambhu M / Peterson, Maria L / Zinn, Steven A / Govoni, Kristen E

Journal of animal science

2022 Volume 100, Issue 6

Abstract: Poor maternal nutrition can negatively affect fetal and placental growth and development. However, the mechanism(s) that contribute to altered placenta growth and function are not well understood. We hypothesized that poor maternal diet would impact ... ...

Abstract	Poor maternal nutrition can negatively affect fetal and placental growth and development. However, the mechanism(s) that contribute to altered placenta growth and function are not well understood. We hypothesized that poor maternal diet would impact signaling through the C-X-C motif chemokine ligand (CXCL) 12-CXCL4 axis and/or placental expression of the insulin-like growth factor (IGF) axis. Using our established sheep model of poor maternal nutrition, we examined the effects of restricted- and over-feeding on ewe placentome gene and protein expression. Specifically, ewes were fed a control (CON; 100%), restricted (RES; 60%), or over (OVER; 140%) diet beginning at day 30.2 ± 0.02 of gestation, and samples were collected at days 45, 90, and 135 of gestation, representing periods of active placentation, peak placental growth, and near term, respectively. Placentomes were separated into cotyledon and caruncle, and samples snap frozen. Protein was determined by western blot and mRNA expression by real-time PCR. Data were analyzed by ANOVA and significance determined at P ≤ 0.05. Ewes fed a RES diet had decreased CXCL12 and vascular endothelial growth factor (VEGF), and increased tumor necrosis factor (TNF)α protein compared with CON ewes in caruncle at day 45 (P ≤0.05). In day 45 cotyledon, CXCR7 protein was increased and mTOR was decreased in RES relative to CON (P ≤0.05). At day 90, CXCR4 and CXCR7 were reduced in RES caruncle compared with CON, whereas VEGF was reduced and mTOR increased in cotyledon of RES ewes relative to CON (P ≤0.05). In OVER caruncle, at day 45 CXCR4 and VEGF were reduced and at day 90 CXCR4, CXCR7, and TNFα were reduced in caruncle compared with CON (P ≤0.05). There was no observed effect of OVER diet on protein abundance in the cotyledon (P > 0.05). Expression of IGF-II mRNA was increased in OVER at day 45 and IGFBP-3 was reduced in RES at day 90 in caruncle relative to CON (P ≤0.05). Maternal diet did not alter placentome diameter or weight (P > 0.05). These findings suggest that restricted- and over-feeding negatively impact protein and mRNA expression of key chemokines and growth factors implicated in proper placenta development and function.
MeSH term(s)	Animals ; Female ; Nutrients ; Placenta/metabolism ; Placentation ; Pregnancy ; RNA, Messenger/metabolism ; Sheep ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	RNA, Messenger ; Vascular Endothelial Growth Factor A ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skac155
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Article ; Online: Structural modeling and functional analysis of the essential ribosomal processing protease Prp from Staphylococcus aureus.

Wall, Erin A / Johnson, Adam L / Peterson, Darrell L / Christie, Gail E

Molecular microbiology

2017 Volume 104, Issue 3, Page(s) 520–532

Abstract: In Firmicutes and related bacteria, ribosomal large subunit protein L27 is encoded with a conserved N-terminal extension that is removed to expose residues critical for ribosome function. Bacteria encoding L27 with this N-terminal extension also encode a ...

Abstract	In Firmicutes and related bacteria, ribosomal large subunit protein L27 is encoded with a conserved N-terminal extension that is removed to expose residues critical for ribosome function. Bacteria encoding L27 with this N-terminal extension also encode a sequence-specific cysteine protease, Prp, which carries out this cleavage. In this work, we demonstrate that L27 variants with an un-cleavable N-terminal extension, or lacking the extension (pre-cleaved), are unable to complement an L27 deletion in Staphylococcus aureus. This indicates that N-terminal processing of L27 is not only essential but possibly has a regulatory role. Prp represents a new clade of previously uncharacterized cysteine proteases, and the dependence of S. aureus on L27 cleavage by Prp validates the enzyme as a target for potential antibiotic development. To better understand the mechanism of Prp activity, we analyzed Prp enzyme kinetics and substrate preference using a fluorogenic peptide cleavage assay. Molecular modeling and site-directed mutagenesis implicate several residues around the active site in catalysis and substrate binding, and support a structural model in which rearrangement of a flexible loop upon binding of the correct peptide substrate is required for the active site to assume the proper conformation. These findings lay the foundation for the development of antimicrobials that target this novel, essential pathway.
MeSH term(s)	Amino Acid Sequence ; Cysteine Proteases/chemistry ; Cysteine Proteases/genetics ; Cysteine Proteases/metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Ribosomal Proteins/chemistry ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Ribosomes/metabolism ; Staphylococcus aureus/enzymology ; Staphylococcus aureus/genetics ; Staphylococcus aureus/metabolism
Chemical Substances	Ribosomal Proteins ; ribosomal proteins L27 ; Cysteine Proteases (EC 3.4.-)
Language	English
Publishing date	2017-05
Publishing country	England
Document type	Journal Article
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/mmi.13644
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Article ; Online: Saddle block anesthetic technique for benign outpatient anorectal surgery.

Peterson, Kent J / Dyrud, Paul / Johnson, Colin / Blank, Jacqueline J / Eastwood, Daniel C / Butterfield, Gail E / Stekiel, Thomas A / Peterson, Carrie Y / Ludwig, Kirk A / Ridolfi, Timothy J

Surgery

2021 Volume 171, Issue 3, Page(s) 615–620

Abstract: Background: Current American Society of Colorectal Surgery Clinical Practice Guidelines for Ambulatory Anorectal Surgery endorse use of monitored anesthesia care, general anesthesia, or spinal anesthesia based on physician and patient preference. ... ...

Abstract	Background: Current American Society of Colorectal Surgery Clinical Practice Guidelines for Ambulatory Anorectal Surgery endorse use of monitored anesthesia care, general anesthesia, or spinal anesthesia based on physician and patient preference. Although several studies support the use of monitored anesthesia care over general anesthesia, the literature regarding spinal anesthesia is limited and heterogenous due to small sample sizes and disparate spinal anesthesia techniques. Saddle block anesthesia is a form of spinal anesthesia that localizes to the lowermost sacral spinal segments allowing for preservation of lower extremity motor function and faster recovery. We accrued one of the largest reported cohort of anorectal procedures using saddle block anesthesia, as such, we sought to evaluate our institutional 12-year experience. Methods: Patients who underwent a benign anorectal procedure at our outpatient surgery center between July 2008-2020 were retrospectively reviewed. Demographics, surgical factors, perioperative times, and adverse events were collected from the electronic medical records. Saddle block anesthesia was generally performed in the preoperative area using a spinal needle (25-27 gauge) and a single injection technique of a 1:1 ratio local anesthetic mixed with 10% dextrose solution. Between 2.5-5 mg of hyperbaric anesthetic was injected intrathecally in the sitting position and the patient remained upright for 3-10 minutes. This technique of saddle block anesthesia provides analgesia for approximately 1-3 hours. Results: In the study, 859 saddle block anesthesia patients were identified, with a mean age of 44.6 years and American Society of Anesthesia score of 1.9; 609 (70.9%) were male. Surgical indications included lesion removal (27.1%), anal fistula (25.8%), hemorrhoidectomy (24.7%), pilonidal disease (6.3%), anal fissure (5.8%), and a combination of prior (10.2%). Prone jackknife positioning was used in 91.6% of procedures. Saddle block anesthesia most often was performed with bupivacaine (48.9%) or ropivacaine (41.7%). The median procedural saddle block anesthesia time was 11 minutes, surgery time was 17 minutes, anesthesia time was 42 minutes, and recovery time was 91 minutes. Patients spent a median of 3 hours and 53 minutes in the facility. Adverse events included urinary retention (1.9%), conversion to general anesthesia (1.8%), spinal headache (1.5%), hemodynamic instability (0.9%), and injection site reaction (0.3%). Conclusion: Demonstrated using the largest known cohort of anorectal patients with saddle block anesthesia, saddle block anesthesia provides an effective method of analgesia to avoid general anesthesia with a low rate of adverse events.
MeSH term(s)	Adult ; Ambulatory Surgical Procedures ; Anesthesia, Spinal/methods ; Anesthetics, Local/administration & dosage ; Bupivacaine/administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Operative Time ; Patient Positioning ; Rectal Diseases/pathology ; Rectal Diseases/surgery ; Retrospective Studies ; Ropivacaine/administration & dosage
Chemical Substances	Anesthetics, Local ; Ropivacaine (7IO5LYA57N) ; Bupivacaine (Y8335394RO)
Language	English
Publishing date	2021-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	202467-6
ISSN	1532-7361 ; 0039-6060
ISSN (online)	1532-7361
ISSN	0039-6060
DOI	10.1016/j.surg.2021.08.066
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Article ; Online: Descriptives and baseline ecological momentary assessed predictors of weight change over the course of psychological treatments for binge eating disorder.

Mason, Tyler B / Smith, Kathryn E / Williams-Kerver, Gail A / Crosby, Ross D / Engel, Scott G / Crow, Scott J / Wonderlich, Stephen A / Peterson, Carol B

Journal of psychosomatic research

2021 Volume 143, Page(s) 110373

Abstract: ... psychological treatments for binge-eating disorder (BED) and to examine baseline predictors (i.e., BED ...

Abstract	Objective: The objectives were to examine individual variability in weight change across psychological treatments for binge-eating disorder (BED) and to examine baseline predictors (i.e., BED symptoms, affect, and appetite) of weight change using ecological momentary assessment (EMA). Method: Adults with BED (N = 110) enrolled in a randomized clinical trial in which they received one of two psychological treatments for BED. At baseline, participants completed a 7-day EMA protocol measuring BED symptoms, affect, and appetite. Height and weight were measured at baseline, mid-treatment, end-of-treatment, and follow-up, and body mass index (BMI) was calculated. Results: On average, participants evidenced a 2% increase in BMI at end-of-treatment and a 1% increase between end-of-treatment and 6-month follow-up assessments. Although results showed that BMI increased over time, the quadratic term reflected a deceleration in this effect. There were interactions between positive affect and the linear trajectory across time predicting BMI, indicating that individuals reporting higher positive affect at baseline evidenced a flatter trajectory of weight gain. There was a main effect of overeating as assessed by EMA and interactions between overeating and linear and quadratic trajectories across time predicting BMI. Individuals who reported greater overeating at baseline had higher BMI across time. However, the BMI of individuals with lower overeating increased linearly, and increases in BMI among those with average or high rates of overeating appeared to stabilize over time. Conclusion: Despite the variability in weight change, baseline positive affect and overeating may be ecological targets for improving weight outcomes in psychological treatments for BED.
MeSH term(s)	Adult ; Binge-Eating Disorder/psychology ; Binge-Eating Disorder/therapy ; Body Mass Index ; Body Weight ; Ecological Momentary Assessment ; Humans ; Male ; Middle Aged
Language	English
Publishing date	2021-01-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80166-5
ISSN	1879-1360 ; 0022-3999
ISSN (online)	1879-1360
ISSN	0022-3999
DOI	10.1016/j.jpsychores.2021.110373
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Article: Differences in Affective Dynamics Among Eating Disorder Diagnostic Groups.

Williams-Kerver, Gail A / Wonderlich, Stephen A / Crosby, Ross D / Cao, Li / Smith, Kathryn E / Engel, Scott G / Crow, Scott J / Peterson, Carol B / Mitchell, James E / Le Grange, Daniel

Clinical psychological science : a journal of the Association for Psychological Science

2020 Volume 8, Issue 5, Page(s) 857–871

Abstract: Emotion regulation theories suggest that affect intensity is crucial in the development and maintenance of eating disorders. However, other aspects of emotional experience, such as lability, differentiation, and inertia, are not as well understood. This ... ...

Abstract	Emotion regulation theories suggest that affect intensity is crucial in the development and maintenance of eating disorders. However, other aspects of emotional experience, such as lability, differentiation, and inertia, are not as well understood. This study is the first to use ecological momentary assessment (EMA) to examine differences in several daily negative affect (NA) indicators among adults diagnosed with anorexia nervosa (AN), bulimia nervosa (BN), or binge eating disorder (BED). Using EMA data from three large studies, a series of linear mixed models showed that participants in the AN and BN groups experienced significantly greater NA intensity and better emotion differentiation than participants in the BED group. Alternatively, the BN group demonstrated significantly greater NA lability than the AN group and greater NA inertia than the BED group. These results suggest that several daily affective experiences differ among eating disorders diagnostic groups and have implications towards distinct conceptualizations and treatments.
Language	English
Publishing date	2020-06-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2682220-9
ISSN	2167-7034 ; 2167-7026
ISSN (online)	2167-7034
ISSN	2167-7026
DOI	10.1177/2167702620917196
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Article ; Online: Familial Hypercholesterolemia in the Electronic Medical Records and Genomics Network: Prevalence, Penetrance, Cardiovascular Risk, and Outcomes After Return of Results.

Dikilitas, Ozan / Sherafati, Alborz / Saadatagah, Seyedmohammad / Satterfield, Benjamin A / Kochan, David C / Anderson, Katherine C / Chung, Wendy K / Hebbring, Scott J / Salvati, Zachary M / Sharp, Richard R / Sturm, Amy C / Gibbs, Richard A / Rowley, Robb / Venner, Eric / Linder, Jodell E / Jones, Laney K / Perez, Emma F / Peterson, Josh F / Jarvik, Gail P /

Rehm, Heidi L / Zouk, Hana / Roden, Dan M / Williams, Marc S / Manolio, Teri A / Kullo, Iftikhar J

Circulation. Genomic and precision medicine

2023 Volume 16, Issue 2, Page(s) e003816

Abstract: Background: The implications of secondary findings detected in large-scale sequencing projects remain uncertain. We assessed prevalence and penetrance of pathogenic familial hypercholesterolemia (FH) variants, their association with coronary heart ... ...

Abstract	Background: The implications of secondary findings detected in large-scale sequencing projects remain uncertain. We assessed prevalence and penetrance of pathogenic familial hypercholesterolemia (FH) variants, their association with coronary heart disease (CHD), and 1-year outcomes following return of results in phase III of the electronic medical records and genomics network. Methods: Adult participants (n=18 544) at 7 sites were enrolled in a prospective cohort study to assess the clinical impact of returning results from targeted sequencing of 68 actionable genes, including Results: The prevalence of FH-associated pathogenic variants was 1 in 188 (69 of 13,019 unselected participants). Penetrance was 87.5%. The presence of an FH variant was associated with CHD (odds ratio, 3.02 [2.00-4.53]) and premature CHD (odds ratio, 3.68 [2.34-5.78]). At least 1 outcome occurred in 92% of participants; 44% received a new diagnosis of FH and 26% had treatment modified following return of results. Conclusions: In a multisite cohort of electronic health record-linked biobanks, monogenic FH was prevalent, penetrant, and associated with presence of CHD. Nearly half of participants with an FH-associated variant received a new diagnosis of FH and a quarter had treatment modified after return of results. These results highlight the potential utility of sequencing electronic health record-linked biobanks to detect FH.
MeSH term(s)	Adult ; Humans ; Proprotein Convertase 9/genetics ; Electronic Health Records ; Penetrance ; Cardiovascular Diseases ; Prevalence ; Prospective Studies ; Risk Factors ; Hyperlipoproteinemia Type II/diagnosis ; Hyperlipoproteinemia Type II/epidemiology ; Hyperlipoproteinemia Type II/genetics ; Coronary Artery Disease/genetics ; Heart Disease Risk Factors ; Genomics
Chemical Substances	PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Journal Article
ISSN	2574-8300
ISSN (online)	2574-8300
DOI	10.1161/CIRCGEN.122.003816
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Article ; Online: The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

Vom Saal, Frederick S / Antoniou, Michael / Belcher, Scott M / Bergman, Ake / Bhandari, Ramji K / Birnbaum, Linda S / Cohen, Aly / Collins, Terrence J / Demeneix, Barbara / Fine, Anne Marie / Flaws, Jodi A / Gayrard, Veronique / Goodson, William H / Gore, Andrea C / Heindel, Jerrold J / Hunt, Patricia A / Iguchi, Taisen / Kassotis, Christopher D / Kortenkamp, Andreas /

Environmental health perspectives

2024 Volume 132, Issue 4, Page(s) 45001

Abstract: Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to : Objectives: We identify the flaws in the assumptions that the German BfR, as well as the ... ...

Abstract	Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to Objectives: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government-academic program model. Discussion: We strongly endorse EFSA's revised TDI for BPA and support the European Commission's (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere. https://doi.org/10.1289/EHP13812.
MeSH term(s)	Humans ; Benzhydryl Compounds ; Food Safety ; No-Observed-Adverse-Effect Level ; Phenols ; Systematic Reviews as Topic
Chemical Substances	Benzhydryl Compounds ; bisphenol A (MLT3645I99) ; Phenols
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/EHP13812
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Article ; Online: Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing.

Linder, Jodell E / Tao, Ran / Chung, Wendy K / Kiryluk, Krzysztof / Liu, Cong / Weng, Chunhua / Connolly, John J / Hakonarson, Hakon / Harr, Margaret / Leppig, Kathleen A / Jarvik, Gail P / Veenstra, David L / Aufox, Sharon / Chisholm, Rex L / Gordon, Adam S / Hoell, Christin / Rasmussen-Torvik, Laura J / Smith, Maureen E / Holm, Ingrid A /

Miller, Erin M / Prows, Cynthia A / Elskeally, Omar / Kullo, Iftikhar J / Lee, Christopher / Jose, Sheethal / Manolio, Teri A / Rowley, Robb / Padi-Adjirackor, Nana Addo / Wilmayani, Ni Ketut / City, Brittany / Wei, Wei-Qi / Wiesner, Georgia L / Rahm, Alanna Kulchak / Williams, Janet L / Williams, Marc S / Peterson, Josh F

American journal of human genetics

2023 Volume 110, Issue 11, Page(s) 1950–1958

Abstract: As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for ... ...

Abstract	As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.
MeSH term(s)	Adult ; Humans ; Female ; Prospective Studies ; Patient Acceptance of Health Care ; Arrhythmias, Cardiac ; Breast Neoplasms/genetics ; Cardiomyopathies/genetics
Language	English
Publishing date	2023-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2023.10.006
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