ABSTRACT
Congenital heart disease (CHD) is present in 1% of live births, yet identification of causal mutations remains challenging. We hypothesized that genetic determinants for CHDs may lie in the protein interactomes of transcription factors whose mutations cause CHDs. Defining the interactomes of two transcription factors haplo-insufficient in CHD, GATA4 and TBX5, within human cardiac progenitors, and integrating the results with nearly 9,000 exomes from proband-parent trios revealed an enrichment of de novo missense variants associated with CHD within the interactomes. Scoring variants of interactome members based on residue, gene, and proband features identified likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied and co-activated cardiac developmental genes, and the identified GLYR1 missense variant disrupted interaction with GATA4, impairing inĀ vitro and inĀ vivo function in mice. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating genetic variants in heart disease.
Subject(s)
GATA4 Transcription Factor/metabolism , Heart Defects, Congenital , Nuclear Proteins/metabolism , Oxidoreductases/metabolism , Transcription Factors , Animals , Heart Defects, Congenital/genetics , Mice , Mutation , Proteomics , T-Box Domain Proteins/genetics , Transcription Factors/geneticsABSTRACT
Chronic inflammation and tissue fibrosis are common responses that worsen organ function, yet the molecular mechanisms governing their cross-talk are poorly understood. In diseased organs, stress-induced gene expression changes fuel maladaptive cell state transitions1 and pathological interaction between cellular compartments. Although chronic fibroblast activation worsens dysfunction in the lungs, liver, kidneys and heart, and exacerbates many cancers2, the stress-sensing mechanisms initiating transcriptional activation of fibroblasts are poorly understood. Here we show that conditional deletion of the transcriptional co-activator Brd4 in infiltrating Cx3cr1+ macrophages ameliorates heart failure in mice and significantly reduces fibroblast activation. Analysis of single-cell chromatin accessibility and BRD4 occupancy in vivo in Cx3cr1+ cells identified a large enhancer proximal to interleukin-1Ć (IL-1Ć, encoded by Il1b), and a series of CRISPR-based deletions revealed the precise stress-dependent regulatory element that controls Il1b expression. Secreted IL-1Ć activated a fibroblast RELA-dependent (also known as p65) enhancer near the transcription factor MEOX1, resulting in a profibrotic response in human cardiac fibroblasts. In vivo, antibody-mediated IL-1Ć neutralization improved cardiac function and tissue fibrosis in heart failure. Systemic IL-1Ć inhibition or targeted Il1b deletion in Cx3cr1+ cells prevented stress-induced Meox1 expression and fibroblast activation. The elucidation of BRD4-dependent cross-talk between a specific immune cell subset and fibroblasts through IL-1Ć reveals how inflammation drives profibrotic cell states and supports strategies that modulate this process in heart disease and other chronic inflammatory disorders featuring tissue remodelling.
ABSTRACT
In diseased organs, stress-activated signalling cascades alter chromatin, therebyĀ triggering maladaptive cell state transitions. Fibroblast activation is a common stress response in tissues that worsens lung, liver, kidney and heart disease, yet its mechanistic basis remains unclear1,2. Pharmacological inhibition of bromodomain and extra-terminal domain (BET) proteins alleviates cardiac dysfunction3-7, providing a tool to interrogate and modulate cardiac cell states as a potential therapeutic approach. Here we use single-cell epigenomic analyses of hearts dynamically exposed to BET inhibitors to reveal a reversible transcriptional switch that underlies the activation of fibroblasts. Resident cardiac fibroblasts demonstrated robust toggling between the quiescent and activated state in a manner directly correlating with BET inhibitor exposure and cardiac function. Single-cell chromatin accessibility revealed previously undescribed DNA elements, the accessibility of which dynamically correlated with cardiac performance. Among the most dynamic elements was an enhancer that regulated the transcription factor MEOX1, which was specifically expressed in activated fibroblasts, occupied putative regulatory elements of a broad fibrotic gene program and was required for TGFĆ-induced fibroblast activation. Selective CRISPR inhibition of the single most dynamic cis-element within the enhancer blocked TGFĆ-induced Meox1 activation. We identify MEOX1 as a central regulator of fibroblast activation associated with cardiac dysfunction and demonstrate its upregulation after activation of human lung, liver and kidney fibroblasts. The plasticity and specificity of BET-dependent regulation of MEOX1 in tissue fibroblasts provide previously unknown trans- and cis-targets for treating fibrotic disease.
Subject(s)
Enhancer Elements, Genetic , Fibroblasts/cytology , Heart Diseases/genetics , Homeodomain Proteins/metabolism , Transcription Factors/metabolism , Animals , Chromatin/metabolism , Epigenomics , Gene Expression Regulation , Humans , Mice , Proteins/antagonists & inhibitors , Single-Cell Analysis , Transcriptome , Transforming Growth Factor beta/metabolismABSTRACT
Mutations in DNAJB6 are a well-established cause of limb girdle muscular dystrophy type D1 (LGMD D1). Patients with LGMD D1 develop progressive muscle weakness with histology showing fibre damage, autophagic vacuoles, and aggregates. Whilst there are many reports of LGMD D1 patients, the role of DNAJB6 in the muscle is still unclear. In this study, we developed a loss of function zebrafish model in order to investigate the role of Dnajb6. Using a double dnajb6a and dnajb6b mutant model, we show that loss of Dnajb6 leads to a late onset muscle weakness. Interestingly, we find that adult fish lacking Dnajb6 do not have autophagy or myofibril defects, however, they do show mitochondrial changes and damage. This study demonstrates that loss of Dnajb6 causes mitochondrial defects and suggests that this contributes to muscle weakness in LGMD D1. These findings expand our knowledge of the role of Dnajb6 in the muscle and provides a model to screen novel therapies for LGMD D1.
Subject(s)
Disease Models, Animal , HSP40 Heat-Shock Proteins , Mitochondria , Molecular Chaperones , Muscle Weakness , Muscular Dystrophies, Limb-Girdle , Zebrafish , Animals , Humans , Autophagy/genetics , HSP40 Heat-Shock Proteins/genetics , HSP40 Heat-Shock Proteins/metabolism , Mitochondria/metabolism , Mitochondria/genetics , Mitochondria/pathology , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Muscle Weakness/genetics , Muscle Weakness/pathology , Muscle Weakness/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Dystrophies, Limb-Girdle/genetics , Muscular Dystrophies, Limb-Girdle/metabolism , Muscular Dystrophies, Limb-Girdle/pathology , Mutation , Nerve Tissue Proteins , Zebrafish/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolismABSTRACT
OBJECTIVE: To implement the BREASTChoice decision tool into the electronic health record and evaluate its effectiveness. BACKGROUND: BREASTChoice , is a multilevel decision tool that: 1) educates patients about breast reconstruction; 2) estimates personalized risk of complications; 3) clarifies patient preferences; and 4) informs clinicians about patients' risk and preferences. METHODS: A multisite randomized controlled trial enrolled adult women with stage 0-III breast malignancy undergoing mastectomy. Participants were randomized to BREASTChoice or a control website. A survey assessed knowledge, preferences, decisional conflict, shared decision-making, preferred treatment, and usability. We conducted intent-to-treat (ITT), per-protocol (PP) analyses (those randomized to BREASTChoice who accessed the tool), and stratified analyses. RESULTS: 23/25 eligible clinicians enrolled. 369/761 (48%) contacted patients enrolled and were randomized. Patients' average age was 51 years; 15% were older than 65. BREASTChoice participants had higher knowledge than control participants (ITT: mean 70.6 vs. 67.4, P =0.08; PP: mean 71.4 vs. 67.4, P =0.03), especially when stratified by site (ITT: P =0.04, PP: P =0.01), age (ITT: P =0.04, PP: P =0.02), and race (ITT: P =0.04, PP: P =0.01). BREASTChoice did not improve decisional conflict, match between preferences and treatment, or shared decision-making. In PP analyses, fewer high-risk patients using BREASTChoice chose reconstruction. BREASTChoice had high usability. CONCLUSIONS: BREASTChoice is a novel decision tool incorporating risk prediction, patient education, and clinician engagement. Patients using BREASTChoice had higher knowledge; older adults and those from racially minoritized backgrounds especially benefitted. There was no impact on other decision outcomes. Future studies should overcome implementation barriers and specifically examine decision outcomes among high-risk patients.
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BACKGROUND: It is unclear how patient-reported outcomes (PROs) change longitudinally after breast cancer surgery. We sought to compare trends in PROs among patients who underwent lumpectomy versus mastectomy over the first year after surgery. PATIENTS AND METHODS: Newly diagnosed stage 0-III female patients with breast cancer who underwent lumpectomy or mastectomy at an academic breast center between June 2019 and March 2023 were invited to participate in a longitudinal PRO study. Enrolled patients received the BREAST-Q™ module, a validated tool measuring domains, such as satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Scores for each domain were compared between the lumpectomy and mastectomy groups over the first year after surgery. Linear mixed models were used to estimate the change in PRO scores over time. RESULTS: The cohort included 203 who underwent lumpectomy and 144 who underwent mastectomy. Patients who underwent lumpectomy were older, more likely to receive adjuvant radiation and endocrine therapy, and less likely to receive adjuvant chemotherapy. Patients who underwent lumpectomy demonstrated greater increases in scores over time for satisfaction with breasts, psychosocial well-being, and sexual well-being compared with patients who underwent mastectomy, after adjusting for the abovementioned covariates and receipt of reconstruction. The lumpectomy group had a larger decline in physical well-being over time compared with the mastectomy group. CONCLUSIONS: Patients who underwent lumpectomy demonstrated greater satisfaction with their breasts, psychosocial well-being, and sexual well-being but worse physical well-being over the first year after surgery compared with patients who underwent mastectomy. These results may help inform early-stage breast cancer patients making decisions about their surgical care.
Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Mastectomy , Patient Reported Outcome Measures , Quality of Life , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Breast Neoplasms/psychology , Middle Aged , Longitudinal Studies , Follow-Up Studies , Aged , Patient Satisfaction , Prognosis , AdultABSTRACT
BACKGROUND: Many women eligible for breast conservation therapy (BCT) elect unilateral mastectomy (UM) with or without contralateral prophylactic mastectomy (CPM) and cite a desire for "peace of mind." This study aimed to characterize how peace of mind is defined and measured and how it relates to surgical choice. METHODS: Nine databases were searched for relevant articles through 8 October 2023, and data were extracted from articles meeting the inclusion criteria. RESULTS: The inclusion criteria were met by 20 studies.Ā Most were prospective cohort studies (65%, 13/20). In the majority of the studies (72%, 13/18), Non-Hispanic white/Caucasian women comprised 80 % or more of the study's sample. Almost half of the studies used the phrase "peace of mind" in their publication (45%, 9/20), and few directly defined the construct (15%, 3/20). Instead, words representing an absence of peace of mind were common, specifically, "anxiety" (85%, 17/20), "fear" (75%, 15/20), and "concern" (75%, 15/20). Most of the studies (90%, 18/20) measured peace of mind indirectly using questionnaires validated for anxiety, fear, worry, distress, or concern, which were administered at multiple postoperative time points (55%, 11/20). Most of the studies (95%, 18/19) reported at least one statistically significant result showing no difference in peace of mind between BCT, UM, and/or CPM at their latest time of assessment. CONCLUSION: Peace of mind is largely framed around concepts that suggest its absence, namely, anxiety, fear, and concern. Existing literature suggests that peace of mind does not differ among average-risk women undergoing BCT, UM, or CPM. Shared surgical decisions should emphasize at least comparable emotional and/or psychosocial well-being between CPM and breast conservation.
Subject(s)
Breast Neoplasms , Mastectomy , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/psychology , Mastectomy/psychology , Anxiety/psychology , Anxiety/prevention & control , Fear/psychology , Prophylactic Mastectomy/psychology , PrognosisABSTRACT
INTRODUCTION: As outcomes for breast cancer patients improve, addressing the side effects and distress of treatment can optimize survivorship. Although distress in breast cancer is well known in literature, there is a lack of information on how these concerns change through the phases of the cancer care continuum. Therefore, this study investigates the longitudinal trajectory of worry in patients with nonmetastatic breast cancer. METHODS: Female patients with newly diagnosed stage I-III breast cancer comprised a mixed-methods, longitudinal study at a cancer center from June 2019 to June 2023. Patients completed an open-ended survey regarding their top three concerns. Responses were obtained before surgery and twoĀ weeks, three, six, nineĀ months, and oneĀ year postoperatively. Responses were qualitatively coded and analyzed to determine themes of cancer-related distress. RESULTS: Participants (nĀ =Ā 262) were aged an average 57.53Ā y (Ā±12.54), 65.8% had stage I disease at diagnosis, and 91.1% were White. Responses revealed that patients' top three sources of concerns varied by treatment phase. Overall, patients were worried about their cancer diagnosis and the risk of recurrence. Preoperatively, patients were worried about treatment timeline, while postoperative concerns transitioned to physical appearance and surgical side effects. CONCLUSIONS: Breast cancer patients consistently reported worries about cancer diagnosis, recurrence, and metastasis as well as the side effects and fear of treatments. However, patient worry appeared to be intrinsically linked with their treatment phase. Therefore, support and interventions should be catered to reflect the changing patterns of patients' sources of distress to optimize breast cancer patients' quality of life.
Subject(s)
Breast Neoplasms , Mastectomy , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/psychology , Middle Aged , Aged , Longitudinal Studies , Adult , Mastectomy/psychology , Mastectomy/adverse effects , Anxiety/etiology , Anxiety/psychology , Anxiety/epidemiology , Qualitative Research , Quality of Life , Surveys and Questionnaires/statistics & numerical data , Neoplasm Recurrence, Local/psychology , Neoplasm Recurrence, Local/epidemiologyABSTRACT
Plant diseases are among the major causes of crop yield losses around the world. To confer disease resistance, conventional breeding relies on the deployment of single resistance (R) genes. However, this strategy has been easily overcome by constantly evolving pathogens. Disabling susceptibility (S) genes is a promising alternative to R genes in breeding programs, as it usually offers durable and broad-spectrum disease resistance. In Arabidopsis, the S gene DMR6 (AtDMR6) encodes an enzyme identified as a susceptibility factor to bacterial and oomycete pathogens. Here, we present a model-to-crop translational work in which we characterize two AtDMR6 orthologs in tomato, SlDMR6-1 and SlDMR6-2. We show that SlDMR6-1, but not SlDMR6-2, is up-regulated by pathogen infection. In agreement, Sldmr6-1 mutants display enhanced resistance against different classes of pathogens, such as bacteria, oomycete, and fungi. Notably, disease resistance correlates with increased salicylic acid (SA) levels and transcriptional activation of immune responses. Furthermore, we demonstrate that SlDMR6-1 and SlDMR6-2 display SA-5 hydroxylase activity, thus contributing to the elucidation of the enzymatic function of DMR6. We then propose that SlDMR6 duplication in tomato resulted in subsequent subfunctionalization, in which SlDMR6-2 specialized in balancing SA levels in flowers/fruits, while SlDMR6-1 conserved the ability to fine-tune SA levels during pathogen infection of the plant vegetative tissues. Overall, this work not only corroborates a mechanism underlying SA homeostasis in plants, but also presents a promising strategy for engineering broad-spectrum and durable disease resistance in crops.
Subject(s)
Disease Resistance/immunology , Plant Diseases/immunology , Plant Diseases/microbiology , Plant Proteins/metabolism , Sequence Homology, Amino Acid , Solanum lycopersicum/immunology , Arabidopsis Proteins/metabolism , Biocatalysis , Gene Expression Regulation, Plant , Gentisates/metabolism , Solanum lycopersicum/genetics , Solanum lycopersicum/growth & development , Mutation/genetics , Phylogeny , Plant Immunity/genetics , Plant Proteins/genetics , Plants, Genetically Modified , Salicylic Acid/metabolism , Transcriptome/genetics , Up-Regulation , Xanthomonas/physiologyABSTRACT
BACKGROUND: Since their development, integrated plastic and reconstructive surgery (PRS) residency training programs have established diverse methods of incorporating general surgery training into graduate medical education. Programs have questioned the necessary duration and timing of such training. The aim of this study is to assess the landscape of general surgery exposure in integrated PRS residency programs. METHODS: Thirty-six integrated PRS residency programs were included based on the availability of postgraduate year (PGY)-level rotation data. Rotations were measured in units of weeks with descriptive titles maintained as advertised by the program. Individual general surgery rotations were also categorized as being either PRS-aligned, American Board of Plastic Surgery (ABPS) Required Clinical (RC) or ABPS Strongly Suggested (SS). Statistical analyses were carried out on the relative proportions of each subcategory in the 2 parent groups. RESULTS: All 36 programs evaluated required general surgery rotations in years PGY- 1 to -2. By PGY-3, 69% of programs required general surgery, and by PGY-6, 25%, and these were limited to 4- to 6-week rotations in burn, breast, or trauma. Looking across all 6 years, with 312 weeks of training total, the minimum number of weeks spent in general surgery rotations was 32, and the maximum number was 119, with an average of 61 weeks (Ā±21).Programs were subcategorized into 2 groups based on whether they spent more (n = 16) or less (n = 20) than the net average number of weeks in ABPS RC + SS rotations. No significant difference was found in the relative proportion of PRS-aligned general surgery across groups. Programs with <60 weeks of general surgery had a relatively greater proportion of ABPS RC and SS rotations. CONCLUSIONS: These data demonstrate that there exists significant variability in overall duration of general surgery training across integrated PRS training programs. When controlling overall general surgery exposure for variables of interest like PRS-aligned exposure or compatibility with ABPS requirements, we found no discernable educational model or patterns to explain the observed range in exposure. These results warrant reexamination of an ideal general surgery track within the integrated plastic surgery training model that optimizes training for the PRS resident.
Subject(s)
Burns , General Surgery , Internship and Residency , Surgery, Plastic , Humans , United States , Surgery, Plastic/education , Curriculum , Education, Medical, GraduateABSTRACT
PURPOSE: To summarize and critique research on the experiences and outcomes of sexual minority women (SMW) treated with surgery for breast cancer through systematic literature review. METHODS: A comprehensive literature search identified studies from the last 20 years addressing surgical experiences and outcomes of SMW breast cancer survivors. Authors performed a quality assessment and thematic content analysis to identify emergent themes. RESULTS: The search yielded 121 records; eight qualitative studies were included in the final critical appraisal. Quality scores for included studies ranged 6-8 out of 10. Experiences and outcomes of SMW breast cancer survivors were organized by major themes: 1) Individual, 2) Interpersonal, 3) Healthcare System, and 4) Sociocultural and Discursive. CONCLUSIONS: SMW breast cancer survivors have unique experiences of treatment access, decision-making, and quality of life in survivorship. SMW breast cancer survivors' personal values, preferences, and support network are critical considerations for researchers and clinicians.
Subject(s)
Breast Neoplasms , Cancer Survivors , Sexual and Gender Minorities , Humans , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Female , Sexual and Gender Minorities/psychology , Sexual and Gender Minorities/statistics & numerical data , Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Qualitative Research , Quality of LifeABSTRACT
BACKGROUND: Turning the Page on Breast Cancer (TPBC) uses a multilevel approach to reduce breast cancer (BC) mortality among Black women. TPBC intervenes by (1) improving health care facilities' ability to conduct effective BC screening, follow-up, and treatment; (2) involving community-based organizations; and (3) providing education and personal risk information through a culturally relevant website. Ohio has among the worst BC mortality rates in the United States for Black women. TPBC is in its third year of providing targeted interventions in 12 Ohio counties with particularly high BC rates among Black women. METHODS: TPBC enrolls health care facilities, collects organizational and patient data, and conducts key informant interviews to inform the provision of appropriate evidence-based interventions. TPBC engages Black communities through community-based organizations and social media advertising. The TPBC website offers BC information, connects Black women to community BC resources, and provides access to a risk-assessment tool. RESULTS: TPBC has provided tailored information packets, evidence-based interventions, and systematic support for improving the tracking and follow-up of breast health care among patients in 10 clinical partnerships. The project has provided education at community events monthly since mid-2021. The TPBC website (http://endbreastcancerohio.org) is promoted through social media (primarily Facebook) and community events to reach Black women aged 25-70 years. To date, 4108 unique users have visited the website, of whom 15.9% completed the risk assessment. CONCLUSIONS: Novel strategies are needed to address persistent disparities in BC outcomes among Black women. TPBC demonstrates the potential effectiveness of multiple methods of community-based, clinic-based, and web-based engagement. PLAIN LANGUAGE SUMMARY: Turning the Page on Breast Cancer (TPBC) aims to reduce breast cancer mortality among Black women in Ohio by conducting multilevel, community-engaged interventions in 12 counties. Women are provided risk information and education at virtual and in-person community events and through a community-friendly website that was launched in November 2020. Almost 4000 women have visited the website, which offers community-targeted information, urges screening for individuals at elevated risk, and offers access to patient navigation services; 655 users have used a breast cancer risk-assessment tool on the site. Community-based organizations conduct educational efforts. TPBC partners with health care facilities, which are taught to improve their ability to conduct effective breast cancer screening, follow-up, and treatment. So far, TPBC has provided educational information, evidence-based intervention lists, tailored information packets, and ongoing quarterly support to partners in 10 counties. Evaluation will focus on aggregated data for screening and genetic testing referral at the clinic level.
Subject(s)
Breast Neoplasms , Female , Humans , Black People , Breast Neoplasms/epidemiology , Breast Neoplasms/ethnology , Breast Neoplasms/mortality , Breast Neoplasms/prevention & control , Educational Status , Ohio/epidemiology , Black or African American/statistics & numerical data , Community Participation , Mass Screening , Risk Assessment , Patient Education as Topic , Health Promotion , Young Adult , Adult , Middle Aged , Aged , Health Status Disparities , Healthcare Disparities , Social Determinants of HealthABSTRACT
BACKGROUND: The rate of contralateral prophylactic mastectomy (CPM) continues to rise despite no improvement in survival, an increased risk of surgical complications, and negative effects on quality of life. This study explored the experiences of the partners of women who undergo CPM. METHODS: This study was part of an investigation into the factors motivating women with early-stage unilateral breast cancer and low genetic risk to opt for contralateral prophylactic mastectomy (CPM). Participating women were asked for permission to invite their partners to take part in interviews. In-depth interviews with partners were conducted using a semi-structured topic guide. A thematic analysis of the data was performed RESULTS: Of 35 partners, all men, 15 agreed to be interviewed. Most perceived their role to be strong and logical. Some hoped their wives would choose a bilateral mastectomy. All felt strongly that the final decision was up to their partners. The partners often framed the decision for CPM as one of life or death. Thus, any aesthetic effects were unimportant by comparison. The male partners had difficulty grasping the physical and emotional changes inherent in mastectomy, which made communicating about sexuality and intimacy very challenging for the couples. In the early recovery period, some noted the stress of managing home life. CONCLUSIONS: The experiences of the male partners provide insight into how couples navigate complex treatment decision-making, both together and separately. There may be a benefit to including partners in pre- and post-surgical counseling to mitigate miscommunication regarding the expected oncologic and emotional outcomes related to CPM.
Subject(s)
Breast Neoplasms , Prophylactic Mastectomy , Male , Female , Humans , Mastectomy/psychology , Breast Neoplasms/prevention & control , Breast Neoplasms/surgery , Breast Neoplasms/genetics , Quality of Life , Decision MakingABSTRACT
BACKGROUND: Little is known about how the quality of decisions influences patient-reported outcomes (PROs). We hypothesized that higher decision quality for breast reconstruction would be independently associated with better PROs. METHODS: We conducted a prospective cohort study of patients undergoing mastectomy with or without reconstruction. Patients were enrolled before surgery and followed for 18 months. We used BREAST-Q scales to measure PROs and linear regression models to explore the relationship between decision quality (based on knowledge and preference concordance) and PROs. Final models were adjusted for baseline BREAST-Q score, radiation, chemotherapy, and major complications. RESULTS: The cohort included 101 patients who completed baseline and 18-month surveys. Breast reconstruction was independently associated with higher satisfaction with breasts (ĆĀ =Ā 20.2, pĀ =Ā 0.0002), psychosocial well-being (ĆĀ =Ā 14.4, pĀ =Ā 0.006), and sexual well-being (ĆĀ =Ā 15.7, pĀ =Ā 0.007), but not physical well-being. Patients who made a high-quality decision had similar PROs as patients who did not. Among patients undergoing mastectomy with reconstruction, higher decision quality was associated with lower psychosocial well-being (ĆĀ =Ā -14.2, pĀ =Ā 0.01). CONCLUSIONS: Breast reconstruction was associated with better PROs in some but not all domains. Overall, making a high-quality decision was not associated with better PROs. However, patients who did not have reconstruction had a trend toward better well-being after making a high-quality decision, whereas patients who did have reconstruction had poorer well-being after making a high-quality decision. Additional research on the relationship between decision quality and PROs is needed.
Subject(s)
Breast Neoplasms , Mammaplasty , Humans , Female , Mastectomy/psychology , Prospective Studies , Breast Neoplasms/surgery , Patient Satisfaction , Quality of Life , Mammaplasty/psychology , Patient Reported Outcome MeasuresABSTRACT
INTRODUCTION: In this embedded substudy of a longitudinal, randomized controlled trial, we sought to evaluate the effects of patient engagement and results feedback on longitudinal patient-reported outcome (PRO) survey completion rates. METHODS: Newly diagnosed stage 0-III breast cancer patients seen at an academic breast center between June 2019 and December 2021 were invited to participate in a longitudinal PRO study. Participants were emailed the BREAST-Q survey, a validated PRO scale, preoperatively and at regular intervals during their postoperative course. Patients were randomized into the intervention group, who received survey results upon completion, or the control group, who received no feedback. The primary endpoint was postoperative survey completion rate. An intention to treat analysis was performed and a quasi-Poisson regression was used to compare rates of longitudinal survey completion between the two groups. RESULTS: Of the 253 patients offered the preoperative survey, 115 were in the intervention group and 138 were in the control group. Postoperative survey completion rate was 54% for the intervention group and 47% for the control group. There was no significant difference in longitudinal postoperative survey completion rate between the two groups (rate ratio 1.10; 95% confidence interval [CI] 0.93-1.31). CONCLUSIONS: In this prospective randomized controlled study, patients did not complete surveys at a higher rate when their survey results were shared with them, suggesting that viewing these results without appropriate clinical context does not generate significant enhancement in patient engagement. Effective interventions to improve survey response rate must be identified to better evaluate PROs.
Subject(s)
Patient Reported Outcome Measures , Research Design , Humans , Prospective StudiesABSTRACT
Measuring quality of life (QOL) after cranioplasty is increasingly evident as a necessary component of patient-centered care. For data to be useful in clinical decision-making and approval of new therapies, studies must utilize valid and reliable instruments. Our objective was to critically appraise studies evaluating QOL in adult cranioplasty patients and determine validity and relevance of the patient-reported outcome measures (PROMs) used. Electronic databases of PubMed, Embase, CINAHL, and PsychINFO were used to identify PROMs measuring QOL in adult patients with cranioplasty. The methodological approach, cranioplasty outcomes, and domains measured by the PROMs were extracted and summarized descriptively. A content analysis of the identified PROMs was completed to identify the concepts measured. From 2236 articles identified, 17 articles containing eight QOL PROMs met the inclusion criteria. None of the PROMs was specifically validated or developed for adults undergoing cranioplasty. The QOL domains included physical health, psychological health, social health, and general QOL. These four domains encompassed 216 total items among the PROMs. Appearance was only assessed in two PROMs. To our knowledge, there are currently no validated PROMs that comprehensively measure appearance, facial function, and adverse effects in adults undergoing cranioplasty. There is an urgent need to develop PROMs to measure QOL outcomes rigorously and comprehensively in this patient population to inform clinical care, research, and quality improvement initiatives. Findings from this systematic review will be used to derive an outcome instrument containing important concepts related to QOL in patients who undergo cranioplasty.
Subject(s)
Patient Reported Outcome Measures , Plastic Surgery Procedures , Adult , Humans , Clinical Decision-Making , Databases, Factual , Mental Health , Quality of Life/psychology , MethylmethacrylateABSTRACT
INTRODUCTION: BREASTChoice is a web-based breast reconstruction decision aid. The previous clinical trial-prior to the adaptation of this refined tool in which we explored usability-measured decision quality, quality of life, patient activation, shared decision making, and treatment choice. The current usability study was designed to elicit patients' and clinicians' perspectives on barriers and facilitators for implementing BREASTChoice into the clinical workflow. METHODS: We conducted qualitative interviews with patients and clinicians from two Midwestern medical specialty centers from August 2020 to April 2021. Interviews were first double coded until coders achieved a kappa > 0.8 and percent agreement > 95%, then were coded independently. We used a sociotechnical framework to evaluate BREASTChoice's implementation and sustainability potential according to end-users, human-computer interaction, and contextual factors. RESULTS: Twelve clinicians and ten patients completed interviews. Using the sociotechnical framework we determined the following. People Using the Tool: Patients and clinicians agreed that BREASTChoice could help patients make more informed decisions about their reconstruction and prepare better for their first plastic surgery appointment. Workflow and Communications: They felt that BREASTChoice could improve communication and process if the patient could view the tool at home and/or in the waiting room. Clinicians suggested the information from BREASTChoice about patients' risks and preferences be included in the patient's chart or the clinician electronic health record (EHR) inbox for accessibility during the consultation. Human Computer Interface: Patients and clinicians stated that the tool contains helpful information, does not require much time for the patient to use, and efficiently fills gaps in knowledge. Although patients found the risk profile information helpful, they reported needing time to read and digest. CONCLUSION: BREASTChoice was perceived as highly usable by patients and clinicians and has the potential for sustainability. Future research will implement and test the tool after integrating the stakeholder-suggested changes to its delivery process and content. It is critical to conduct usability assessments such as these prior to decision aid implementation to ensure success of the tool to improve risk communication.
Subject(s)
Mammaplasty , User-Computer Interface , Humans , Quality of Life , Patient Participation , Communication , Decision MakingABSTRACT
BACKGROUND: Among independent plastic surgery graduates, most have general surgery training, but the utility of American Board of Surgery (ABS) certification in plastic surgery practice is unclear. We elucidated attitudes and trends of ABS certification in American Board of Plastic Surgery diplomates. METHODS: American Board of Plastic Surgery diplomates from 2018 to 2020 were reviewed to identify independent plastic surgery graduates. These graduates were anonymously surveyed regarding demographics, employment, fellowships, practices, and attitudes toward ABS certification. RESULTS: Of 568 American Board of Plastic Surgery diplomates, 223 independent graduates (39%) were identified. Sixty-eight percent of these graduates were ABS certified, 80% of whom achieved certification during the beginning of plastic and reconstructive surgery training; 41% were fellowship trained. About half are in private practice, 25% are part of a hospital group, and 17% work in universities. Of 223 independent graduates, 54 (24.4%) completed the survey; 85.2% reported ABS certification, and 21.7% perform general surgery procedures. Most stated that general surgery training was valuable to their career, regardless of certification. Most agreed that ABS certification benefited their career; 63% plan to recertify. Of those surveyed, 59.3% had completed a plastic surgery fellowship. Non-fellowship-trained surgeons felt more strongly that ABS certification was beneficial (P = 0.014) and valued by patients (P = 0.026) compared with fellowship-trained surgeons. CONCLUSIONS: American Board of Surgery certification is a priority to independent plastic surgery trainees, despite potential disruption to training, personal costs, and unclear utility to their practice. Although few perform general surgery procedures, most plan to recertify. Future studies should investigate recertification among surgeons later in their careers and the impacts of dual board certification on plastic surgery practice.
Subject(s)
Plastic Surgery Procedures , Surgery, Plastic , Humans , Certification , Emotions , Fellowships and ScholarshipsABSTRACT
BACKGROUND: Management of nonfatal ballistic facial trauma is well described in the literature for wounds secondary to military combat. However, there is little literature describing such management in civilian practice. We aimed to describe nonmilitary patients with recent nonfatal facial injuries from ballistic trauma using the California Office of Statewide Health Planning and Development patient database. METHODS: A retrospective study was performed using the California Office of Statewide Health Planning and Development Ambulatory Surgery and Inpatient datasets. All adults with the International Classification of Diseases, 10th Revision codes of severe nonfatal facial trauma from firearms requiring emergent surgery during 2016-2018 were included. Outcomes assessed include number and type of facial procedures performed, hospital length of stay, number of admissions, timing of definitive management, and lifetime hospitalization costs. RESULTS: A total of 331 traceable patients were identified over this 3-year period. The average age was 35.4 years (SD, 15.2), and 87% were male. The median index admission length of stay was 8 days (interquartile range, 3-15 days). Subsequent readmission was required for 123 (37.2%) patients with 10% mortality in the index admission. Total median charges per patient for all admissions were $257,804 (interquartile range, $105,601-$531,916). A total of 215 patients (65%) had at least 1 facial repair performed. Of all 331 patients, 64.3% underwent musculoskeletal repair (n = 213), 31.4% underwent digestive system repair (n = 104), and 29.6% underwent respiratory system repair (n = 98). The average number of repairs per patient was 2.52 (SD, 3.38), with 35% not having any of the specified International Classification of Diseases, 10th Revision repair codes. A total of 27% of patients had 1 procedure performed, whereas 38% received 2 or more, for an average of 3.87 (SD, 3.5) repairs over the study duration. DISCUSSION: To our knowledge, this is the first assessment of civilian characteristics of nonfatal ballistic facial trauma in California. Nonfatal facial ballistic trauma results in complex injuries to multiple body systems, requiring long admissions, costly hospital stays, and coordination of care across several surgical specialties. Many patients require a variety of procedures over multiple admissions, highlighting the overall morbidity of these injuries. Future studies will look at how care for these patients differs between various hospitals and geographic regions and whether current civilian management aligns with well-defined military reconstructive protocols for facial ballistic injuries.
Subject(s)
Facial Injuries , Adult , United States , Humans , Male , Female , Retrospective Studies , Incidence , Facial Injuries/epidemiology , Facial Injuries/surgery , Face , Length of StayABSTRACT
Neurofeedback training is a common treatment option for attention deficit hyperactivity disorder (ADHD). Given theta/beta-based neurofeedback (T/B NF) training targets at the electrophysiological characteristics of children with ADHD, benefits for attention may be expected. PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science were searched through December 31, 2020. Studies were evaluated with Risk of Bias tools. Within-group effects based on Pre- and Post-treatment comparisons of the Intervention Group, and Between-group effects based on the between-group differences from Pre-treatment to Post-treatment were calculated. Nineteen studies met selection criteria for systematic review, 12 of them were included in meta-analysis. Within-group effects were medium at Post-treatment and large at Follow-up. Between-group analyses revealed that T/B NF was superior to waitlist control and physical activities, but not stimulant medication. Results showed that T/B NF has benefits for attention in children with ADHD, however, cautions should be taken when interpreting the findings.