Publications by authors named "Karen Lyons"

198 Publications

Parents' Perceptions of Emerging Adults With Congenital Heart Disease: An Integrative Review of Qualitative Studies.

J Pediatr Health Care 2021 Feb 10. Epub 2021 Feb 10.

Background: As the primary caregivers for children with congenital heart disease (CHD), parents' perceptions are important for emerging adults to achieve independence. This integrative review of qualitative studies aimed to describe parents' perceptions of emerging adults with CHD.

Method: Seven electronic databases were searched. Data extraction and quality assessment were performed. A meta-synthesis was conducted to inductively develop essential themes from five included studies.

Results: Three essential themes encompassing the parents' perspective of emerging adults with CHD were: (1) concerns about emerging adults' ability to be independent; (2) concerns about emerging adults' future; and (3) impact of disease on family. The themes depicted parents' concerns and worries about their children's ability to successfully achieve independence, especially in disease self-management and life goals.

Discussion: This review highlights parents' concerns about their emerging adult children's independence. Understanding these concerns allows for developing interventions to facilitate emerging adults' independence and ease parents' worries.
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http://dx.doi.org/10.1016/j.pedhc.2020.11.009DOI Listing
February 2021

Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging.

Cell Stem Cell 2021 Feb 4. Epub 2021 Feb 4.

Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, CA 90095, USA. Electronic address:

Skeletal aging is a complex process, characterized by a decrease in bone formation, an increase in marrow fat, and stem cell exhaustion. Loss of H3K9me3, a heterochromatin mark, has been proposed to be associated with aging. Here, we report that loss of KDM4B in mesenchymal stromal cells (MSCs) exacerbated skeletal aging and osteoporosis by reducing bone formation and increasing marrow adiposity via increasing H3K9me3. KDM4B epigenetically coordinated β-catenin/Smad1-mediated transcription by removing repressive H3K9me3. Importantly, KDM4B ablation impaired MSC self-renewal and promoted MSC exhaustion by inducing senescence-associated heterochromatin foci formation, providing a mechanistic explanation for stem cell exhaustion with aging. Moreover, while KDM4B was required for parathyroid hormone-mediated bone anabolism, KDM4B depletion accelerated bone loss and marrow adiposity induced by a high-fat diet. Our results suggest that the epigenetic rejuvenation and reversing bone-fat imbalance might be new strategies for preventing and treating skeletal aging and osteoporosis by activating KDM4B in MSCs.
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http://dx.doi.org/10.1016/j.stem.2021.01.010DOI Listing
February 2021

Caregivers' Loss of the Dyadic Experience after Their Care Partners' Death.

West J Nurs Res 2021 Jan 29:193945921990426. Epub 2021 Jan 29.

University of South Florida, Tampa, FL, USA.

Little is known about the experience of family caregivers when their care partner dies and their dyadic relationship comes to an end. This study qualitatively examined and characterized the loss of the dyadic experience for the caregiver after the death of their care partner. Data was accrued as part of a randomized clinical trial in 29 older hospice caregivers. Iterative thematic analysis focused on dyadic processes before, during and post death. Using two relational parameters from Relational Turbulence Theory resulted in a preliminary characterization of a new concept-dyadic dissolution as a cognitive and affective process whereby a remaining member of a dyad experiences relational uncertainty and partner interference while adapting (or not) to the death of their care partner. Findings suggest that asking several open-ended questions about the dyadic relationship will enable assessment for any continuing impact of relational uncertainty and partner interference on bereaved caregivers.
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http://dx.doi.org/10.1177/0193945921990426DOI Listing
January 2021

Author Correction: NELL-1 in the treatment of osteoporotic bone loss.

Nat Commun 2021 Jan 13;12(1):453. Epub 2021 Jan 13.

Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California, 90095, USA.

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http://dx.doi.org/10.1038/s41467-021-20933-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806913PMC
January 2021

Feasibility and Acceptability of a Remotely Delivered, Web-Based Behavioral Intervention for Men With Prostate Cancer: Four-Arm Randomized Controlled Pilot Trial.

J Med Internet Res 2020 12 31;22(12):e19238. Epub 2020 Dec 31.

Oregon Health and Science University, Portland, OR, United States.

Background: Diet and exercise may be associated with quality of life and survival in men with prostate cancer.

Objective: This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer.

Methods: We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls-one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes.

Results: In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1.

Conclusions: A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations.

Trial Registration: ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013.
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http://dx.doi.org/10.2196/19238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808895PMC
December 2020

The Validity and Reliability of the Reflux Finding Score.

J Voice 2020 Dec 19. Epub 2020 Dec 19.

Department of Otolaryngology - Head and Neck Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania; Otolaryngology and Communication Sciences Research, Lankenau Institute for Medical Research, Pennsylvania. Electronic address:

Laryngopharyngeal reflux (LPR) disease is common. The incidence of newly diagnosed cases has increased substantially due to awareness and development of new diagnostic measurements. The reflux finding score (RFS) and reflux symptom index (RSI) are believed to be useful in the assessment process, including after the initiation of therapy. However, many authors have suggested concerns about the reliability and validity of the RFS.

Objective: To evaluate the validity and reliability of the RFS.

Methods: Ninety-two patients diagnosed with LPR who had undergone 24-hour pH-Impedance tests were included. All patients underwent stroboscopy and 24-Hour pH-Impedance monitoring within thirty days. Fifty-nine patients filled out a RSI prior to stroboscopic exam. The RFS was determined by four blinded observers: one otolaryngology resident, two laryngology fellows, and one laryngologist. Stroboscopic images were reviewed again one year later to assess intrarater reliability. RFS and RSI were correlated with 24-hour pH Impedance testing.

Results: The Kappa value between reviewers was 0.479. The percent agreement of the four observers for total RFS was 74.04%.The percent agreement between reviewers for subglottic edema was 78.77%; for ventricular obliteration was 65.55%; for erythema/hyperemia was 69.62%, for vocal fold edema was 68.32%; for diffuse laryngeal edema was 66.86%, for posterior commissure hypertrophy was 73.54%; for granuloma/granulation was 96.80%; for thick endolaryngeal mucus was 72.81%. The intrarater reliability of the four observers for total RFS was 67.5% with an intrarater reliability range of 50%-90%. The intrarater reliability for subglottic edema was 85% with a range of 70%-100%; for ventricular obliteration was 77.50% with a range of 70%-90%; for erythema/hyperemia was 65.00% with a range of 50%-90%; for vocal fold edema was 52.50% with a range of 30%-70%; for diffuse laryngeal edema was 62.50% with a range of 20%-80%; for posterior commissure hypertrophy was 52.50% with a range of 10%-80%; for granuloma/granulation was 100%; for thick endolaryngeal mucus was 55.00% with a range of 10%-90%. There was no correlation between RFS and any parameter of the 24-Hr pH-Impedance Test. RSI had a significant correlation with number of upright events (r value of 0.271, R of 0.0733 and P-value of 0.037), total symptoms experienced (r value of 0.0.267, R of 0.0715 and P-value of 0.041), and symptom correlation score (r value of -0.297, R of 0.0884 and P-value of 0.022).

Conclusion: Many authors have expressed concerns about the reliability and validity of the RFS. In our study we found a fair/substantial interrater reliability, and a modest intra-rater reliability. We found no correlation between the RFS and 24-Hr pH Impedance testing. This study suggests that the concerns about the validity and reliability of the RFS may be warranted. This widely used clinical score should be interpreted with caution and further research and refinement should be considered.
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http://dx.doi.org/10.1016/j.jvoice.2020.11.008DOI Listing
December 2020

Trends in integrative medicine and health consults: differences between cancer survivors and patients without cancer.

Support Care Cancer 2020 Oct 14. Epub 2020 Oct 14.

Oregon Health & Science University, School of Nursing, 3455 SW US Veterans Hospital Rd, OR, 97239, Portland, USA.

Objectives: The objectives were to compare patients with and without cancer who sought an integrative health (IH) consult and reasons for seeking a consult.

Design: Descriptive cross-sectional study that employed a secondary analysis of an integrative health database supplemented by a retrospective medical record review.

Setting/location: Integrative Medicine and Health program in a Southwestern United States academic medical center.

Subjects: Eight hundred thirty-nine adults over the age of 18 seeking IH consultation.

Results: The number of complementary therapies reported prior to consult were not significantly different between groups. The most reported complementary therapies used by cancer survivors were multivitamins, exercise, and turmeric. Patients without cancer reported significantly higher pain levels than cancer survivors. Cancer survivors reported significantly higher energy, sleep levels, overall health, spiritual wellbeing, and significantly better relationships compared to patients without cancer. Cancer survivors reported fatigue and cancer as the top reasons for IH consult.

Conclusion: Participants without cancer reported higher levels of pain and lower levels of energy, sleep, overall health, spiritual wellbeing, and relationships compared to cancer survivors. However, cancer survivors still reported levels of unmanaged symptoms. Complementary therapy use prior to IMH consult was similar between groups; however, IMH providers recommended more treatments for patients without cancer. Our results highlight that more evidence is needed to guide IMH recommendations, especially for cancer survivors who may still be in treatment. Additionally, our results support evidence-based recommendations that all cancer survivors should be assessed for complementary therapy use and provided counseling by qualified providers on their advantages and limitations.
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http://dx.doi.org/10.1007/s00520-020-05815-0DOI Listing
October 2020

A Multilevel Modeling Approach to Examine Incongruent Illness Appraisals in Family Care Dyads Over Time.

J Fam Nurs 2020 08 4;26(3):229-239. Epub 2020 Aug 4.

Boston College, Chestnut Hill, MA, USA.

Over the past two decades, there has been movement toward a dyadic perspective of the illness experience. Although multilevel models have led to great insights into how dyads are affected by illness as family units, these models are still underutilized for understanding incongruent illness appraisals. Such incongruent appraisals can have implications for how the dyad collaborates to manage illness, the health of the dyad, and clinical outcomes. The focus of this article is to describe and promote the application of multilevel models to longitudinal dyadic data to understand incongruent illness appraisals over time. In particular, we present a data exemplar so researchers can apply these models to their own data and clinical questions to understand the ways care dyads converge and diverge in their appraisals and determine factors associated with such variability. We comment on the implications and extensions of these models for family nursing research and practice.
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http://dx.doi.org/10.1177/1074840720944439DOI Listing
August 2020

Moderator Role of Mutuality on the Association Between Depression and Quality of Life in Stroke Survivor-Caregiver Dyads.

J Cardiovasc Nurs 2020 Jul 29. Epub 2020 Jul 29.

Gianluca Pucciarelli, PhD, FAHA Research Fellow, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy. Karen S. Lyons, PhD, FGSA Associate Professor, William F. Connell School of Nursing, Boston College, Massachusetts. Silvio Simeone, PhD Research Fellow, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy. Christopher S. Lee, PhD, FAAN, FAHA, FHFSA Professor, William F. Connell School of Nursing, Boston College, Massachusetts. Ercole Vellone, PhD, FESC Associate Professor, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy. Rosaria Alvaro, MSN, FESC, FAAN Professor, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy.

Background: Authors of previous research have not yet analyzed the role of potential moderators in the relationship between depressive symptoms and quality of life (QOL).

Aims: The aim of this study was to examine the moderating effect of mutuality between depressive symptoms and QOL in stroke survivor and caregiver dyads.

Methods: This study used a longitudinal design with 222 stroke survivor-caregiver dyads enrolled at survivor discharge from rehabilitation hospitals. Data collection was performed for 12 months. We examined survivor and caregiver QOL dimensions (physical, psychological, social, and environmental), depression, and mutuality at baseline and every 3 months. Hierarchical linear modeling was used to test 4 longitudinal dyadic moderation models (1 for each QOL domain).

Results: Survivors (50% male) and caregivers (65% female) were 70.8 (SD, 11.9) and 52.5 (SD, 13.1) years old, respectively. We observed no significant moderating effects of mutuality for survivors across the 4 dimensions of QOL over time. However, higher survivor mutuality was significantly associated with higher survivor psychological and social QOL at baseline. Regarding caregivers, caregiver mutuality significantly moderated the association between caregiver depressive symptoms and caregiver physical (B = 0.63, P < .05), psychological (B = 0.63, P < .01), and social (B = 0.95, P < .001) QOL at baseline, but not in environmental QOL. Higher caregiver mutuality was significantly associated with less improvement in caregiver physical QOL over time.

Conclusions: Mutuality is a positive variable on the association between depression and QOL for both members of the dyad at discharge but may lead to declines in physical health for caregivers over time. Further work is needed to understand the role of mutuality on long-term outcomes and associations with increased care strain.
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http://dx.doi.org/10.1097/JCN.0000000000000728DOI Listing
July 2020

Development of the Breast Cancer Stigma Scale for Arab Patients.

Asia Pac J Oncol Nurs 2020 Jul-Sep;7(3):295-300. Epub 2020 Jun 26.

School of Nursing Boston College, Chestnut Hill, MA, USA.

Objective: Health-related stigma is associated with depression, but there is a lack of studies examining the stigma of cancer in Arab patients. The purpose of this study was to establish the reliability and validity of a newly developed, culturally sensitive measure of stigma among Arab women with breast cancer.

Methods: The sample consisted of 59 Arab women with breast cancer who were Muslim, on active oncology treatment. The mean age of women was 49 years (standard deviation = 8.31). Content validity was assessed by calculating a Content Validity Index (CVI) based on ratings from seven oncology experts. Convergent validity was assessed by examining the association with a measure of depressive symptoms. Reliability was assessed by calculating Cronbach's alpha.

Results: The measure demonstrated strong content validity (item-CVIs ranged from 0.85 to 1.0 and the scale-CVI was 1.0) and good convergent validity (higher levels of stigma were significantly associated with higher levels of depressive symptoms). Finally, the reliability of the measure was also found to be adequate (alpha = 0.79).

Conclusions: The initial examination of the Breast Cancer Stigma Scale for Arab Patients indicated that the scale is both valid and reliable to be used in Arab women with breast cancer.
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http://dx.doi.org/10.4103/apjon.apjon_14_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325776PMC
June 2020

CCN1/Cyr61 Is Required in Osteoblasts for Responsiveness to the Anabolic Activity of PTH.

J Bone Miner Res 2020 11 17;35(11):2289-2300. Epub 2020 Aug 17.

Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

CCN1/Cyr61 is a dynamically expressed matricellular protein that serves regulatory functions in multiple tissues. Previous studies from our laboratory demonstrated that CCN1 regulates bone maintenance. Using an osteoblast and osteocyte conditional knockout mouse model (Ccn1 ), we found a significant decrease in trabecular and cortical bone mass in vivo, in part through suppression of Wnt signaling since the expression of the Wnt antagonist sclerostin (SOST) is increased in osteoblasts lacking CCN1. It has been established that parathyroid hormone (PTH) signaling also suppresses SOST expression in bone. We therefore investigated the interaction between CCN1 and PTH-mediated responses in this study. We find that loss of Ccn1 in osteoblasts leads to impaired responsiveness to anabolic intermittent PTH treatment in Ccn1 mice in vivo and in osteoblasts from these mice in vitro. Analysis of Ccn1 mice demonstrated a significant decrease in parathyroid hormone receptor-1 (PTH1R) expression in osteoblasts in vivo and in vitro. We investigated the regulatory role of a non-canonical integrin-binding domain of CCN1 because several studies indicate that specific integrins are critical to mechanotransduction, a PTH-dependent response, in bone. These data suggest that CCN1 regulates the expression of PTH1R through interaction with the αvβ3 and/or αvβ5 integrin complexes. Osteoblasts that express a mutant form of CCN1 that cannot interact with αvβ3/β5 integrin demonstrate a significant decrease in mRNA and protein expression of both PTH1R and αv integrin. Overall, these data suggest that the αvβ3/β5-binding domain of CCN1 is required to endow PTH signaling with anabolic activity in bone cells. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4128DOI Listing
November 2020

Patterns of Dyadic Appraisal of Decision-Making Involvement of African American Persons Living with Dementia.

Gerontologist 2020 Jul 1. Epub 2020 Jul 1.

Connell School of Nursing, Boston College, Chestnut Hill, MA.

Background And Objectives: Greater everyday decision-making involvement by persons living with dementia (PLWD) and congruent appraisal between PLWDs and their caregivers have been associated with better quality of life (QOL) for both members of the dyad. However, no study has examined the association between the appraisals of everyday decision-making involvement of PLWDs and their QOL among African Americans.

Research Design And Methods: A secondary analysis of cross-sectional data from 62 African American dementia dyads was conducted. Multilevel and latent class mixture modeling were used to characterize dyadic appraisal of the decision-making involvement of African American PLWDs and identify distinct patterns thereof.

Results: Three distinct patterns were observed. "Incongruent, PLWD Low Involvement" labeled in 19.4% of the sample, 53.2% were labeled "Incongruent, PLWD Moderate Involvement;" and 27.4% were labeled "Congruent, PLWD High Involvement." The Congruent, PLWD High Involvement pattern consisted of PLWDs who were significantly younger and had significantly less cognitive impairment than PLWDs in the other patterns. In the Incongruent, PLWD Moderate Involvement pattern, PLWDs had significantly better QOL than PLWDs in the Incongruent, PLWD Low Involvement pattern but QOL did not significantly differ from PLWDs in the Congruent, PLWD High Involvement pattern.

Discussion And Implications: There is a need to tailor strategies to optimize QOL in African American dementia dyads. While increasing everyday decision-making involvement for PLWDs in the Incongruent, PLWD Low Involvement pattern is an important goal, other strategies may be needed to improve QOL of PLWDs in the remaining patterns.
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http://dx.doi.org/10.1093/geront/gnaa086DOI Listing
July 2020

CTGF/CCN2 facilitates LRP4-mediated formation of the embryonic neuromuscular junction.

EMBO Rep 2020 08 17;21(8):e48462. Epub 2020 Jun 17.

Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.

At the neuromuscular junction (NMJ), lipoprotein-related receptor 4 (LRP4) mediates agrin-induced MuSK phosphorylation that leads to clustering of acetylcholine receptors (AChRs) in the postsynaptic region of the skeletal muscle. Additionally, the ectodomain of LRP4 is necessary for differentiation of the presynaptic nerve terminal. However, the molecules regulating LRP4 have not been fully elucidated yet. Here, we show that the CT domain of connective tissue growth factor (CTGF/CCN2) directly binds to the third beta-propeller domain of LRP4. CTGF/CCN2 enhances the binding of LRP4 to MuSK and facilitates the localization of LRP4 on the plasma membrane. CTGF/CCN2 enhances agrin-induced MuSK phosphorylation and AChR clustering in cultured myotubes. Ctgf-deficient mouse embryos (Ctgf ) have small AChR clusters and abnormal dispersion of synaptic vesicles along the motor axon. Ultrastructurally, the presynaptic nerve terminals have reduced numbers of active zones and mitochondria. Functionally, Ctgf embryos exhibit impaired NMJ signal transmission. These results indicate that CTGF/CCN2 interacts with LRP4 to facilitate clustering of AChRs at the motor endplate and the maturation of the nerve terminal.
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http://dx.doi.org/10.15252/embr.201948462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403661PMC
August 2020

Patterns of Heart Failure Dyadic Illness Management: The Important Role of Gender.

J Cardiovasc Nurs 2020 Sep/Oct;35(5):416-422

Background: The ways in which patients with heart failure (HF) and their care partners work together to manage HF are often overlooked.

Objective: The aim of this study was to identify and compare different patterns of HF dyadic illness management.

Methods: This was a secondary analysis of data on HF dyads. Heart failure management was measured using patient and care partner versions of the Self-Care of HF Index and European HF Self-care Behavior Scale. Latent class modeling was used to identify patterns of HF dyadic management.

Results: The mean age of the 62 patients and their care partners was 59.7 ± 11.8 and 58.1 ± 11.9 years, respectively. A majority of patients (71.0%) had class III/IV HF, and a majority of the couples (95.2%) were married. Two distinct dyadic patterns were observed, 1 collaborative management type (n = 42, 67.7%) and 1 autonomous management type (n = 20, 32.3%). Dyads in the autonomous pattern were mostly female patients with male care partners; patients in this pattern also were more anxious and depressed, and reported worse relationship quality compared with collaborative dyads.

Conclusion: There is an engendered spectrum of collaboration in how HF patient-care partner dyads work together to manage HF that needs to be considered in clinical care and research.
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http://dx.doi.org/10.1097/JCN.0000000000000695DOI Listing
June 2020

Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification.

JCI Insight 2020 07 9;5(13). Epub 2020 Jul 9.

Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.

Heterotopic ossification (HO) is defined as abnormal differentiation of local stromal cells of mesenchymal origin, resulting in pathologic cartilage and bone matrix deposition. Cyr61, CTGF, Nov (CCN) family members are matricellular proteins that have diverse regulatory functions on cell proliferation and differentiation, including the regulation of chondrogenesis. However, little is known regarding CCN family member expression or function in HO. Here, a combination of bulk and single-cell RNA sequencing defined the dynamic temporospatial pattern of CCN family member induction within a mouse model of trauma-induced HO. Among CCN family proteins, Wisp1 (also known as Ccn4) was most upregulated during the evolution of HO, and Wisp1 expression corresponded with chondrogenic gene profile. Immunohistochemistry confirmed WISP1 expression across traumatic and genetic HO mouse models as well as in human HO samples. Transgenic Wisp1LacZ/LacZ knockin animals showed an increase in endochondral ossification in HO after trauma. Finally, the transcriptome of Wisp1-null tenocytes revealed enrichment in signaling pathways, such as the STAT3 and PCP signaling pathways, that may explain increased HO in the context of Wisp1 deficiency. In sum, CCN family members, and in particular Wisp1, are spatiotemporally associated with and negatively regulate trauma-induced HO formation.
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http://dx.doi.org/10.1172/jci.insight.135432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406255PMC
July 2020

Role of Spirituality on the Association Between Depression and Quality of Life in Stroke Survivor-Care Partner Dyads.

Circ Cardiovasc Qual Outcomes 2020 Jun 26;13(6):e006129. Epub 2020 May 26.

William F. Connell School of Nursing, Boston College, MA (C.S.L., K.S.L.).

Background: Little is known about the protective effect of spirituality on the association between known risk factors such as depression and quality of life (QOL) in stroke survivor-care partner dyads. Therefore, the aim of this study was to evaluate the moderating role of spirituality on the association between depressive symptomatology and QOL in stroke survivor-care partner dyads.

Methods And Results: Longitudinal design with 223 stroke survivor-care partner dyads enrolled at survivor discharge from rehabilitation hospitals. Data collection was performed over 12 months. We measured survivors' and care partners' depression, quality of life, and spirituality. Examining the moderating role of spirituality on the association between depressive symptoms and QOL within survivor-care partner dyads, we used a traditional Actor-Partner-Interdependence Model and a basic Actor-Partner-Interdependence Model moderation model for a mixed variable. Survivors (51% male) and care partners (66% female) were 70.7 and 52.3 years old, respectively. The survivor's spirituality significantly moderated the association between care partner depressive symptomatology and survivor psychological QOL (B=0.03, <0.05) and moderated the association between care partner depressive symptoms and care partner physical (B=0.05, <0.001) and psychological (B=0.04, <0.001) QOL. The care partner's own level of spirituality was significantly positively associated with their physical QOL (B=0.28, <0.001).

Conclusions: The findings from this study have broad implications for the role of spirituality in relation to QOL in medical-health contexts and the importance of examining such concepts within a dyadic framework. Greater awareness of the importance of spirituality among clinicians and nurses may improve cultural competence in healthcare services.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006129DOI Listing
June 2020

TGFβ as a gatekeeper of BMP action in the developing growth plate.

Bone 2020 08 20;137:115439. Epub 2020 May 20.

Department of Orthopaedic Surgery and Orthopaedic Institute for Children, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States of America; Department of Molecular, Cell and Developmental Biology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States of America. Electronic address:

The ligands that comprise the Transforming Growth Factor β superfamily highly govern the development of the embryonic growth plate. Members of this superfamily activate canonical TGFβ and/or BMP (Bone Morphogenetic Protein) signaling pathways. How these pathways interact with one another is an area of active investigation. These two signaling pathways have been described to negatively regulate one another through crosstalk involving Smad proteins, the primary intracellular effectors of canonical signaling. More recently, a mechanism for regulation of the BMP pathway through TGFβ and BMP receptor interactions has been described. Here in this review, we demonstrate examples of how TGFβ is a gatekeeper of BMP action in the developing growth plate at both the receptor and transcriptional levels.
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http://dx.doi.org/10.1016/j.bone.2020.115439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891678PMC
August 2020

Identifying unique profiles of perceived dyspnea burden in heart failure.

Heart Lung 2020 Sep - Oct;49(5):488-494. Epub 2020 May 18.

William F. Connell School of Nursing, Boston College, 140 Commonwealth Avenue, Maloney Hall, Chestnut Hill, MA  02467, United States. Electronic address:

Background: Dyspnea is a common symptom of heart failure (HF) but dyspnea burden is highly variable.

Objectives: Identify distinct profiles of dyspnea burden and identify predictors of dyspnea symptom profile.

Methods: A secondary analysis of data from five studies completed at Oregon Health and Science University was conducted. The Heart Failure Somatic Perception Scale was used to measure dyspnea burden. Latent class mixture modeling identified distinct profiles of dyspnea burden in a sample of HF patients (n = 449). Backwards stepwise multinomial logistic regression identified predictors of latent profile membership.

Results: Four profiles of dyspnea burden were identified: no dyspnea/not bothered by dyspnea, mild dyspnea, moderate exertional dyspnea, and moderate exertional dyspnea with orthopnea and PND. Higher age was associated with greater likelihood of not being bothered by dyspnea than having moderate exertional dyspnea with orthopnea and PND. Higher NYHA class, anxiety, and depression were associated with greater likelihood of greater dyspnea burden.

Conclusions: Burden of dyspnea is highly variable among HF patients. Clinicians should account for the nuances of dyspnea and the activities that induce dyspnea when assessing HF patients.
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http://dx.doi.org/10.1016/j.hrtlng.2020.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483352PMC
March 2021

Benefits of a Self-Management Program for the Couple Living With Parkinson's Disease: A Pilot Study.

J Appl Gerontol 2020 May 13:733464820918136. Epub 2020 May 13.

Oregon Health & Science University, Portland, USA.

The goal of this pilot study was to explore health benefits for couples participating together in an existing community-based self-management workshop for Parkinson's disease (PD). A quasi-experimental two-wave design explored the effects of the program in comparison to a wait-list control condition. Preliminary data ( = 39 couples) showed that spouses in the intervention group had greater engagement in mental relaxation techniques at 7 weeks than those in the control condition (large effect size). Small effects were observed for increases in aerobic activity and mental relaxation for the adult with PD, increases in strength-based activities and self-efficacy for spouses, declines in depressive symptoms for spouses, and decreases in protective buffering for both adults with PD and spouses. The program showed potential for existing community-based programs to benefit couples living with chronic illness.
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http://dx.doi.org/10.1177/0733464820918136DOI Listing
May 2020

Correction to: FoxD1-driven CCN2 deletion causes axial skeletal deformities, pulmonary hypoplasia, and neonatal asphyctic death.

J Cell Commun Signal 2020 Mar;14(1):47-52

Department. Pathology, University Medical Centre Utrecht, Heidelberglaan, 100 3584 CX, Utrecht, The Netherlands.

Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs. Differentiation of FoxD1-progenitor derived pericytes into myofibroblasts involves CCN2 expression and contributes importantly to maladaptive tissue remodeling in for example kidney and lung fibrosis models. To generate a model for studying the contribution of CCN2 expression in FoxD1-progenitor derived cells to development of fibrotic tissue remodeling, we set out to establish a FoxD1Cre - CCN2 mouse colony. However, all double-transgenic mice died soon after birth due to asphyxia. Histopathological examination revealed a reduction in alveolar space and lung weight, and subtle axial (thoracic and cervical) skeletal deformities. Together with the previously reported association of a FoxD1 containing locus with human adolescent idiopathic scoliosis, our data suggest that the fatal pulmonary hypoplasia resulting from selective deletion of CCN2 from FoxD1-progenitor derived mesenchymal cells developed secondary to impaired breathing movements due to aberrant axial skeletogenesis.
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http://dx.doi.org/10.1007/s12079-020-00559-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176786PMC
March 2020

Physical and Mental Quality of Life in Patients With End-Stage Liver Disease and Their Informal Caregivers.

Clin Gastroenterol Hepatol 2021 Jan 11;19(1):155-161.e1. Epub 2020 Apr 11.

William F. Connell School of Nursing, Boston College, Boston, Massachusetts.

Background & Aims: Management of end-stage liver disease (ESLD) has implications for not only patients' quality of life (QOL), but also their caregivers'. We aimed to identify characteristics of patients with ESLD and their caregivers that are associated with QOL.

Methods: We obtained cross-sectional baseline data from patients and their caregivers (132 dyads; 62% were married or partners), recruited from outpatient hepatology clinics within 2 healthcare centers. Patients were included if their model for end-stage liver disease score was 15 or more; caregivers were identified by the patient as the primary informal caregiver. QOL was measured by the SF-36 and relationship quality using the mutuality scale. We measured uncertainty using the uncertainty in illness scales for patients and caregivers. Multilevel modeling was used to analyze the data.

Results: Refractory ascites was associated with worse physical QOL for patients (unstandardized beta [B], -9.19; standard error [SE], 2.28) and caregivers (B, -5.41; SE, 2.33); history of hepatic encephalopathy was associated with worse patient physical QOL (B, -3.86; SE, 1.65). High levels of uncertainty were associated with worse physical and mental QOL for both members of the dyads; relationship quality was significantly associated with patient mental QOL (B, 2.73; SE, 1.19).

Conclusions: Clinicians and researchers should consider the effects of ESLD on caregivers as well as their patients to optimize the QOL for both.
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http://dx.doi.org/10.1016/j.cgh.2020.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554075PMC
January 2021

Patient and caregiver contributions to self-care in multiple chronic conditions: A multilevel modelling analysis.

Int J Nurs Stud 2020 Mar 14:103574. Epub 2020 Mar 14.

Campus Bio-Medico University of Rome, Rome, Italy. Electronic address:

Background: Multiple chronic conditions (MCC) are highly prevalent worldwide, especially among older populations. Patient self-care and care partner (or caregiver) contributions to self-care are recommended to reduce the impact of MCC and improve patients' outcomes.

Objectives: To describe patient self-care and care partner contributions to self-care and to identify determinants of patient self-care and care partner contributions to self-care at the patient and care partner level.

Design: Multicentre cross-sectional study.

Setting: Outpatient and community settings in Italy.

Participants: A sample of 340 patients with MCC and care partner dyads was recruited between 2017 and 2018.

Methods: We measured patient's self-care and care partner contributions to self-care in dyads using the Self-care of Chronic Illness Inventory and the Caregiver Contribution to Self-care of Chronic Illness Inventory. To control for dyadic interdependence, we performed a multilevel modelling analysis.

Results: Patients' and care partners' mean ages were 76.65 (± 7.27) and 54.32 (± 15.25), respectively. Most care partners were female and adult children or grandchildren. The most prevalent chronic conditions in patients were diabetes (74%) and heart failure (34%). Patients and care partners reported higher levels of self-care monitoring than self-care maintenance and management behaviours. Important patient clinical determinants of self-care included cognitive status, number of medications and type of chronic condition. Care partner determinants of self-care contributions included age, gender, education, perceived income, care partner burden, caregiving hours per week and the presence of a secondary care partner.

Conclusions: Our findings support the importance of taking a dyadic approach when focusing on patients with MCC and their care partners. More dyadic longitudinal research is recommended to reveal the modifiable determinants of self-care and the complex relationships between patients and care partners in the context of MCC.
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http://dx.doi.org/10.1016/j.ijnurstu.2020.103574DOI Listing
March 2020

Navigating sexual health in cancer survivorship: a dyadic perspective.

Support Care Cancer 2020 Nov 10;28(11):5429-5439. Epub 2020 Mar 10.

College of Public Health and Human Sciences, Oregon State University, 2250 SW Jefferson Way, Corvallis, OR, 97331, USA.

Purpose: This qualitative study examined how young adult breast cancer survivors (YABCS) and their partners appraised and managed their sexual health and intimate relationships after cancer.

Methods: We conducted concurrent, individual telephone interviews with 25 YABCS and their male partners. We utilized a thematic, inductive analysis to examine individual interviews, followed by analysis within and across couples to identify dyadic themes. We explored how themes mapped on to the Theory of Dyadic Illness Management to build a conceptual model specific to the sexual health challenges of young adult couples living with cancer.

Results: Our analysis revealed five interconnected themes: (1) shared understanding of physical and psychological challenges of sexual health after cancer, (2) navigating role shifts and changes to sexual relationship, (3) getting through it as a team, (4) maintaining open communication, and (5) need for services and support for partners/caregivers and couples.

Conclusion: Both survivors and their partners articulated physical (e.g., painful sex, decreased libido) and psychological (e.g., guilt, self-consciousness) challenges to their sexual health in survivorship. Our dyadic focus revealed a spectrum of ways that couples managed the changes to their relationships and sexual health, highlighting "open communication" and strategies for "working as a team" as critical. There is no "one size fits all" solution, as individuals and couples cope with and manage these challenges in different ways. Study results can inform couple-focused intervention strategies, such as creating shared understanding of sexual health after cancer and improving communication skills.
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http://dx.doi.org/10.1007/s00520-020-05396-yDOI Listing
November 2020

Hospice Use Among Individuals With Severe Persistent Mental Illness.

J Am Psychiatr Nurses Assoc 2020 Mar 6:1078390320910482. Epub 2020 Mar 6.

Karen S. Lyons, PhD, FGSA, Boston College, Chestnut Hill, MA, USA.

Severe persistent mental illness (SPMI) currently affects an estimated 11.2 million adults in the United States (National Institute of Mental Health, 2019). Affected individuals are known to experience inequities in care, and on average, they die earlier than individuals without SPMI. Currently, little is known about hospice use among individuals with SPMI, including what factors contribute to the use of hospice services. The aim of this integrated review was to identify factors associated with the use of hospice services by individuals with SPMI. A review of the available literature on this topic was performed in accordance with PRISMA guidelines. The databases Cumulative Index to Nursing and Allied Health Literature, PubMed, and PsycInfo were searched, and relevant records were identified. Ultimately, eight studies were identified and selected for analysis. Themes illustrating the factors associated with hospice use and, within them, challenges to obtaining hospice care were discovered. The three themes identified within the eight studies were fragmentation of care, inadequate communication, and the need for advance care planning. These patterns indicated that multiple barriers to utilizing hospice care exist for individuals with SPMI when compared with the general population. By recognizing and addressing factors influencing the use of hospice care, as well as barriers to receiving hospice, improved provision of timely end-of-life care that is consistent with individuals' preferences may be facilitated.
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http://dx.doi.org/10.1177/1078390320910482DOI Listing
March 2020

Understanding the family care dyad: A comparison of two multilevel models.

Eur J Cardiovasc Nurs 2020 02;19(2):178-184

William F. Connell School of Nursing, Boston College, USA.

Although there has been increasing attention on a dyadic perspective of illness, contemporary dyadic research methods are still rarely utilized in cardiovascular disease. The focus of this paper is to describe the advantages of two types of multilevel dyadic models (the matched pairs model and the lesser known incongruence model). Data exemplars in a sample of heart failure family dyads are used to illustrate the distinct advantages of these two related multilevel dyadic models with particular emphasis on alignment with research questions. The more commonly known matched pairs model examines separate outcomes for each member of the dyad, controlling for the interdependent nature of the data. By re-parameterizing this model into a univariate dyadic outcomes model, researchers can address distinct, and sometimes more appropriate, research questions (e.g. incongruent appraisals of the illness experience). This paper promotes greater application of these methods in cardiovascular research to further understanding of the dyadic experience and more appropriately target interventions.
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http://dx.doi.org/10.1177/1474515120902368DOI Listing
February 2020

Trajectories of Self-reported Physical Functioning and Symptoms in Lung Cancer Survivors.

Cancer Nurs 2021 Mar-Apr 01;44(2):E83-E89

Author Affiliations: School of Nursing (Ms Medysky and Drs Dieckmann and Winters-Stone), Knight Cancer Institute (Drs Winters-Stone and Sullivan), and Division of Pulmonary and Critical Care Medicine, Department of Medicine (Dr Sullivan), Oregon Health & Science University, Portland; and Health Services & Research Development, Veterans Affairs Portland Health Care System, Oregon (Dr Sullivan); and Connell School of Nursing, Boston College, Chestnut Hill, Massachusetts (Dr Lyons).

Background: Lung cancer survivors are at risk of accelerated declines in physical functioning attributed to cancer treatment. However, it is unknown whether patients experience the same rate of functional decline and how symptoms may contribute to different trajectories.

Objectives: The aims of this study were to identify interindividual differences in the pattern and rate of change in self-reported functioning in lung cancer survivors and examine whether and how symptoms are related to physical functioning over time.

Methods: This was a secondary data analysis in 72 lung cancer survivors. Multilevel modeling was used to estimate trajectories of self-reported physical functioning over 1 year and assess the relation between functioning, fatigue, depressive symptoms, and pain severity across time.

Results: Within the sample, average physical functioning did not significantly decrease (coefficient, -0.46; 95% confidence interval [CI] = -2.85 to 0.94) over time. However, among individual lung cancer survivors, baseline physical functioning varied significantly (SD, 20.76; 95% CI, 16.84-25.59) and changed at significantly different rates over 1 year (SD, 3.50; 95% CI, 2.13-5.68). Fatigue, assessed over 1 year, was the only significant symptom predictor of physical functioning changes over time (coefficient = 1.03; 95% CI, 0.79-1.27).

Conclusions: In this sample of lung cancer survivors, not all survivors experienced the same rate of self-reported functional decline and those with lower levels of fatigue reported better physical functioning.

Implications For Practice: Nurses should recognize that some lung cancer survivors may have faster rates of functional declines than others, which may be related to fatigue severity. Early identification and management of fatigue could help avoid or delay future disability.
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http://dx.doi.org/10.1097/NCC.0000000000000765DOI Listing
February 2020

FoxD1-driven CCN2 deletion causes axial skeletal deformities, pulmonary hypoplasia, and neonatal asphyctic death.

J Cell Commun Signal 2020 Feb 4. Epub 2020 Feb 4.

Deparment Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.

Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs. Differentiation of FoxD1-progenitor derived pericytes into myofibroblasts involves CCN2 expression and contributes importantly to maladaptive tissue remodeling in e.g. kidney and lung fibrosis models. To generate a model for studying the contribution of CCN2 expression in FoxD1-progenitor derived cells to development of fibrotic tissue remodeling, we set out to establish a FoxD1Cre - CCN2 mouse colony. However, all double-transgenic mice died soon after birth due to asphyxia. Histopathological examination revealed a reduction in alveolar space and lung weight, and subtle axial (thoracic and cervical) skeletal deformities. Together with the previously reported association of a FoxD1 containing locus with human adolescent idiopathic scoliosis, our data suggest that the development of fatal pulmonary hypoplasia caused by selective deletion of CCN2 from FoxD1-progenitor derived mesenchymal cells was secondary to aberrant axial skeletogenesis.
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http://dx.doi.org/10.1007/s12079-020-00549-4DOI Listing
February 2020

Interpersonal relationship challenges among stroke survivors and family caregivers.

Soc Work Health Care 2020 02 22;59(2):91-107. Epub 2020 Jan 22.

College of Nursing, University of Cincinnati, Cincinnati, Ohio, USA.

A strong interpersonal relationship after stroke is important for the well-being of survivors and family caregivers. However, as many as 54% of families experience relationship problems after stroke and as many as 38% of couples experience overt conflict. The purpose of this study is to enhance understanding about relationship challenges among stroke dyads and to identify implications for direct practice in social work. Semi-structured interviews were conducted with care dyads. Qualitative data were analyzed through an interpretive description lens. Seven themes about relationship challenges were identified. Findings highlight areas to consider in promoting strong relationships between survivors and family caregivers. Social workers may have the opportunity to assist dyads with disrupting negative communication cycles, strengthening empathy and collaboration, and achieving a balance so that each person's needs are met.
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http://dx.doi.org/10.1080/00981389.2020.1714827DOI Listing
February 2020

Factors influencing quality of life in African-American dementia dyads.

Aging Ment Health 2020 Jan 10:1-8. Epub 2020 Jan 10.

Connell School of Nursing, Boston College, Chestnut Hill, MA, USA.

Both caregivers and the older adults they care for can experience declines in quality of life (QOL) over the course of the dementia trajectory. Little research has examined QOL in African-American caregivers and even less in African-American persons with dementia (PWDs), making it difficult to identify associated factors. Guided by the Negro Family as a Social System framework, a secondary data analysis was used to examine the influence of family structure, instrumental and expressive role functions on QOL in a sample of 62 African-American dementia dyads (i.e. African-American PWDs and their African-American caregivers). Dyadic data were analyzed using multilevel modeling to control for the interdependent nature of the data. On average, African-American PWDs reported significantly worse QOL than African-American caregivers. Within African-American dementia dyads, QOL covaried. African-American PWDs experienced significantly worse QOL when their caregiver was a non-spouse and they themselves perceived less involvement in decision-making. In addition, African-American caregivers experienced significantly worse QOL when they reported greater dyadic strain with the African-American PWD and were non-spouses of African-American PWDs. Findings suggest understanding the interpersonal characteristics (e.g., dyadic relationship, family structure and role functions) of dyads may hold promise for improving their QOL.
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http://dx.doi.org/10.1080/13607863.2020.1711865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347433PMC
January 2020

The role of symptom appraisal, concealment and social support in optimizing dyadic mental health in heart failure.

Aging Ment Health 2020 Jan 10:1-8. Epub 2020 Jan 10.

Boston College, Chestnut Hill, MA, USA.

Heart failure patients and their family care partners experience poor mental health, yet the majority of the research focuses on patients and care partners separately. Guided by the Theory of Dyadic Illness Management, the purpose of the current study was to identify distinct patterns of dyadic mental health in heart failure and identify the individual, dyadic and familial factors associated with group membership. Fifty nine heart failure community-dwelling patients and their spouse care partners were recruited from an outpatient heart failure clinic. Mental health was operationalized by depressive symptoms, measured with the Patient Health Questionnaire-9 (PHQ-9) measure of depression. Distinct groups of dyadic mental health were determined by categorizing depression scores within dyads. Three groups of dyadic mental health were identified: an optimal dyadic mental health group (31%), a poor dyadic mental health group (32%) and an incongruent dyadic mental health group (37%). Patient age, patient fatigue, patient concealment, incongruent dyadic appraisal of pain interference and social/familial support were significantly associated with group membership. Findings underscore the salience of a dyadic approach to health and the clinical relevance of identifying patterns of dyadic mental health so we may determine those most in need of intervention.
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http://dx.doi.org/10.1080/13607863.2020.1711866DOI Listing
January 2020