Browsing by Author "Smith, Asa"
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Item Differential Gene Expression Among Patients With Heart Failure Experiencing Pain(Wolters kluwer Health, 2023-02-26) Smith, Asa; Jung, Miyeon; Pressler, Susan; Mocci, Evelina; Dorsey, SusanBackground: Chronic pain is frequently experienced by patients with heart failure (HF) and is associated with higher mortality, higher symptom burden, and worsened health-related quality of life. However, the genomic mechanisms underlying chronic pain in HF are understudied. Building an understanding of the mechanistic underpinnings of pain may inform novel interventions. Objective: The objective was to identify genes associated with pain from mRNA sequence data collected from patients with HF with and without pain. Methods: The current study analyzed data from 40 patients with HF previously enrolled in a clinical trial. Pain presence was measured using the Health Utilities Index Mark-3. Genes were tested for differential expression using DESeq2, and differentially expressed genes were analyzed for protein–protein interaction (PPI) and relevant ontological pathways using Metascape. Genes located within the core of the PPI network were considered key in disease-relevant biological pathways. Differentially expressed genes within this PPI network were reviewed in existing literature to narrow down candidate genes of interest. These target genes of interest were reanalyzed in a second sample of 24 patients with HF using validation quantitative polymerase chain reaction. Results: A total of 334 genes (279 upregulated, 55 downregulated) were differentially expressed between patients with and without pain in the primary sample of 40. These genes were largely aligned with neutrophil degranulation pathways. Seven genes of interest were identified from a core network of 15 co-expressed genes in the PPI network and existing literature. Three of these seven genes: matrix metallopeptidase 8 (MMP8), proprotein convertase subtilisin/kexin type 9 (PCSK9), and neutrophil defensin 3 (DEFA3) were upregulated in patients with pain versus without pain in both the primary and validation samples. All seven genes of interest are involved in immune, inflammatory, and atherosclerotic processes. Discussion: These results identify potential genes that may play a mechanistic role in chronic pain in HF. Further research is needed to evaluate these potential genes among clearly delineated pain phenotypes.Item Does pain at hospital discharge predict transition from hospital to home and 12-month mortality among patients with heart failure?(N/A, 2022-11) Smith, Asa; Jung, Miyeon; Pressler, SusanIntroduction: Pain is present in 37%-68.9% of hospitalized patients with heart failure (HF), but little is known about how pain at discharge influences transition from hospital to home or 12-month mortality. The aims were to examine if pain at discharge predicts 1) return to home status and 2) 12-monthmortality among hospitalized patients with HF. Methods: In this prospective study, data were obtained from a dataset of 1,475 patients with HF hospitalized at 3 tertiary-care hospitals from 2009-2017. Pain at discharge (yes/no) was obtained from medical records using ICD-9 or ICD-10 codes. Return to home status (yes/no) and all-cause 12-month mortality were obtained from medical records. Descriptive statistics, independent samples t-tests, and χ2 were used to describe the sample. Logistic regression was computed to address the aims. Results: The sample was 59.5% women and 40.5% men. The mean age was 68.6 (SD 13.6) years. Race was 53.6% Black and 46.4% White. Of 1,475 patients, 239 (16.2%) had pain documented at discharge. Patients with pain documented at discharge were younger compared to patients without pain (p<.001). One hundred sixty-five of 239 patients (69.0%) with pain and 831 of1,236 patients (67.2%) without pain returned to home (χ2=0.297, p=.585). At 12 months after discharge, 20 of 239 patients (8.4%) with pain had died compared to 134 of 1,236 patients (10.8%) without pain (χ2=1.31, p=.252). In logistic regressions, pain at hospital discharge was not a statistically significant predictor of return to home status or 12-month mortality (Table 1). Conclusions: Over 30% of patients with HF did not return to home after hospitalization. Patients with HF have significant transitional care needs, including pain management. Future studies are needed to determine the phenotypes of pain among patients with HF, evaluate associations between pain at discharge and transitional care needs, and design innovative strategies to ameliorate pain.Item Does the location of a primary pain complaint during transport by emergency medical services predict hospitalization status, length of stay, and mortality among patients with heart failure?(N/A, 2023-03) Smith, Asa; Jung, Miyeon; Pressler, SusanPurpose: The purpose was to examine which locations of pain (abdominal, back, chest, or generalized) predict hospitalization status, length of stay, and mortality among patients with heart failure (HF) transported by emergency medical services (EMS) to the emergency department (ED). Research Question: Does presenting to EMS with a primary complaint of abdominal, back, chest, or generalized pain predict 1) higher hospital admission rates 2) longer length of stay, or 3) higher mortality rates compared to patients presenting with other primary complaints? Rationale: About 22% of patients with HF are transported by EMS to the ED with a primary complaint of pain. Locations of pain vary among patients with HF, but whether different locations of pain can differentiate health outcomes are unknown. Methods: A retrospective comparative descriptive study was conducted using electronic health records from EMS and hospitals. A total of 2,592 patients with HF transported between 2009-2017 were included in the analysis. Pain complaints included abdominal, back, chest, and generalized. Outcomes were hospitalization status, in-hospital mortality, and inpatient length of stay. Binomial logistic and linear regressions were used to answer research questions. Results: Demographics were mean age 66.15 (SD=14.93); gender 59.7% women, 54.6% men; race 54.6% Black, 44.6% White, 0.8% Other. Of 2,592 patients, 581 (22.4%) presented with pain, 1,886 were hospitalized (72.8%), 127 died during hospitalization (4.9%), and median length of hospital stay was 4.63 days. Pain frequencies were: chest=404 (69.5%), abdominal=100 (17.2%), generalized=45 (7.7%), and back=32 (5.5%). Compared to patients without pain, no locations of pain were significantly associated with hospitalization. Surprisingly, patients with chest pain were less likely to die during hospitalization compared to patients without pain (OR=0.44, p=.024). Furthermore, patients with chest pain (β =-0.49, p<.001) and generalized pain (β =-0.57, p=.011) were associated with a shorter length of stay compared to patients without pain. Conclusion: No locations of pain predicted hospitalization status. Chest pain was associated with decreased odds of in-hospital mortality, and both chest and generalized pain were associated with a shorter length of stay. One explanation may be the higher illness severity among patients with other primary complaints. Prospective studies are needed to understand the impact chronic pain in HF.Item Genes linked with inflammatory processes are differentially expressed in patients with chronic heart failure and pain(N/A, 2022-09) Smith, Asa; Dorsey, Susan; Mocci, Evelina; Jung, Miyeon; Pressler, SusanBackground and Aims Pain is a significant problem among patients with chronic heart failure (HF). The mechanisms underlying pain in HF remain poorly understood. Gene expression analysis using mRNA sequencing can highlight mechanistic underpinnings of complex symptoms such as pain. The aim of this study was to identify differentially expressed genes linked with pain in patients with HF with pain compared with patients with HF but without pain. The research question was: what genes linked with pain are differentially expressed between patients with HF and pain compared to patients with HF without pain? Methods Data were collected as part of a parent randomized controlled trial to test the efficacy of a computerized cognitive intervention for memory among patients with chronic HF (R01 NR016116). Blood specimens, pain measures, and sociodemographic characteristics were collected during the baseline visit in the parent trial. Data from 40 patients with HF: 20 with pain and 20 without pain, were analyzed in the current study. Pain presence (yes/no) was assessed using 1 item of the Health Utilities Index Mark-3 questionnaire. Sociodemographic data collected were age, self-reported gender, race and ethnicity, years of education, marital status, depressive symptoms (Patient Health Questionnaire-8), and health-related quality of life (Minnesota Living with Heart Failure Questionnaire). Clinical characteristics included body mass index, left ventricular ejection fraction (LVEF), and New York Heart Association heart failure class. Differences in demographic and clinical variables between the pain and no pain groups were examined using independent samples t-tests and chi square. The mRNA was isolated from whole blood and sequenced using a 150bppaired-end read configuration. Genes were tested for differential expression between HF patients with pain and without pain using DESeq2. Genes were considered differentially expressed if the log fold change between groups was ≥ ± 0.58 with a false discovery p-value < 0.05. Differentially expressed genes were examined using protein-protein interactions analysis, disease-related biological pathways, and existing pain literature. Independent samples t-tests were used to identify statistically significant differences in gene expression between the pain and no pain groups. Target genes of interest were validated through real-time polymerase chain reaction in a different sample of 24 patients: 10 with pain and 14 without pain, selected from the parent study and matched to the discovery sample on age and gender. Results Among the patients with pain, the mean age was 66.45 ± 6.21 years compared to 62.65 ± 13.87 years in the patients with pain. Most patients were men (60% in the pain group vs. 70% in the no pain group) and White(75% vs. 60%, respectively). The sample was primarily New York Heart Association class II (42.5%), with an average LVEF of 42.56% ± 13.58%. There were no statistically significant differences in demographic or clinical status variables between patients with and without pain. A total of 334 differentially expressed genes were identified (279 upregulated and 55 downregulated); they were mostly involved in neutrophil degranulation pathways (n = 57, false discovery p-value = 7.9e-17), followed by extracellular matrix organization pathways (n = 19, false discovery p-value = 4.5e-03). The protein-protein interactions analysis produced a network of 288 nodes and 497 edges, compared to the expected number of 182 edges(enrichment p-value < 1.0e-16), with a core network consisting of 15 co-expressed genes. From this core network of 15 genes, 7 target genes of interest were identified: (1) cathepsin G (CTSG), (2) lactotransferrin(LTF), (3) lipocalin-2 (LCN2), (4) matrix metallopeptidase 8 (MMP8), (5) matrix metallopeptidase 9 (MMP9), (6)proprotein convertase subtilisin/kexin type 9 (PCSK9), and (7) neutrophil defensin 3 (DEFA3). All 7 genes were connected to inflammatory pathways and inflammatory pain conditions (e.g., arthritis) in existing pain literature. All 7 genes were upregulated in patients with HF and pain compared to those with HF and without pain. Three of these 7 genes (MMP8,PCSK9,andDEFA3) were also validated in the second sample of 24patients with HF. Conclusions This study identified 7 genes that were differentially expressed in patients with chronic HF and pain compared to patients with HF but no pain. Of these, 3 were validated in an additional sample which further strengthens the proposed connection of these genes with pain. The genes were significantly enriched in inflammatory and extracellular matrix organization and may play a role in development of chronic pain among patients with HF. This study is novel in that the biologic mechanisms underlying pain in this population have not been previously examined using gene expression analysis. Further research is needed with a more ethnically diverse sample and more robust pain measures, particularly regarding severity and locations of pain.Item Pain and heart failure during transport by emergency medical services and its associated outcomes: Hospitalization, mortality, and length of stay(SAGE Publications, 2024-01-17) Smith, Asa; Jung, Miyeon; Pressler, SusanBackground: Over 22% of patients with heart failure (HF) are transported by emergency medical services (EMSs) for a primary complaint of pain. The relationship between a primary complaint of pain on hospitalization status, mortality, or length of stay following transport by EMS is understudied. Objectives: The objective of this study was to determine whether a primary complaint of pain during EMS transport predicted hospitalization status, mortality, or inpatient length of stay. Methods: In this retrospective longitudinal cohort study, data were analyzed from electronic health records of 3539 patients with HF. Descriptive statistics and multivariate logistic and linear regression analyses were used to achieve study objectives. Results: Demographics were mean age 64.83 years (standard deviation [SD] = 14.58); gender 57.3% women, 42.7% men; self-reported race 56.2% black, 43.2% white, and 0.7% other. Of 3539 patients, 2346 (66.3%) were hospitalized, 149 (4.2%) died, and the mean length of stay was 6.02 (SD = 7.55) days. A primary complaint of pain did not predict increased odds of in-hospital mortality but did predict 39% lower odds of hospitalization (p < .001), and 26.7% shorter length of stay (p < .001). Chest pain predicted 49% lower odds of hospitalization (p < .001) and 34.1% (p < .001) shorter length of stay, whereas generalized pain predicted 45% lower odds of hospitalization (p = .044) following post-hoc analysis. Conclusions: A primary complaint of chest pain predicted lower odds of hospitalization and shorter length of stay, possibly due to established treatment regimens. Additional research is needed to examine chronic pain rather than a primary complaint of pain.Item Psychometric Evaluation of the Revised Collaboration for Leadership and Innovation in Mentoring Survey in a Diverse PhD Student Sample(N/A, 2024-02) Smith, Asa; Granner, Josephine; Shuman, Clayton; Umberfield, Elizabeth; Lavoie Smith, EllenPurpose The purpose of this study was to evaluate the internal consistency reliability and structural validity of the Collaboration for Leadership and Innovation in Mentoring (CLIM) survey, a measure of PhD mentor/mentee relationship quality. Learning Objective Participants will learn aspects of survey development and psychometric evaluation, including application of principal components analysis Questions/Hypothesis Is the CLIM survey reliable and valid when administered to a diverse sample of PhD students? Theoretical Framework/Rationale Quality mentorship plays a significant role in successful PhD education. Our previously developed 44-item CLIM survey showed preliminary evidence of reliability and validity among nursing PhD students but has not been evaluated using a heterogeneous PhD student population. Methods Of 5,539 PhD students at a large public university, 819 completed the 44-item CLIM survey (response rate 14.8%). Individual item and total scores were described using descriptive statistics (ranges, means, standard deviations). Principal components analysis was used to identify the underlying component structure and reduce the number of items. Internal consistency reliability was evaluated using Cronbach’s alpha. Results The sample was 58.2% male, representing 19 PhD programs with engineering being the most common. Total scores ranged from 15-110 (mean = 81.57; SD = 15.42) (higher scores indicate higher mentorship quality). The survey was reduced to 22 items across 6 components: 1) Working together, 2) Mentor availability, 3) Mentoring teams and goals, 4) Shared research interests, 5) Mutual respect, and 6) Mentor benefit. Internal consistency reliability of the reduced survey was 0.89. Conclusions The findings suggest that the revised 22-item CLIM survey (now called CLIM-22) is a reliable and valid standardized measure of PhD mentorship quality that can be used across heterogeneous PhD programs beyond nursing.