Major ß cell-specific functions of NKX2.2 are mediated via the NK2-specific domain.

The consolidation of unambiguous cell fate commitment relies on the ability of transcription factors (TFs) to exert tissue-specific regulation of complex genetic networks. However, the mechanisms by which TFs establish such precise control over gene expression have remained elusive-especially in instances in which a single TF operates in two or more discrete cellular systems. In this study, we demonstrate that ß cell-specific functions of NKX2.2 are driven by the highly conserved NK2-specific domain (SD). Mutation of the endogenous NKX2.2 SD prevents the developmental progression of ß cell precursors into mature, insulin-expressing ß cells, resulting in overt neonatal diabetes. Within the adult ß cell, the SD stimulates ß cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for ß cell function. These irregularities in ß cell gene expression may be mediated via SD-contingent interactions with components of chromatin remodelers and the nuclear pore complex. However, in stark contrast to these pancreatic phenotypes, the SD is entirely dispensable for the development of NKX2.2-dependent cell types within the CNS. Together, these results reveal a previously undetermined mechanism through which NKX2.2 directs disparate transcriptional programs in the pancreas versus neuroepithelium.

Transgenic ferret models define pulmonary ionocyte diversity and function.

Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans1,2, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-CreERT2::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-CreERT2::CFTRL/L). By comparing these models with cystic fibrosis ferrets3,4, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-CreERT2::CFTRL/L ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl- and HCO3-. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.

Uterine injury during diestrus leads to placental and embryonic defects in future pregnancies in mice†.

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at ~30% of deliveries in the USA and projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes that ultimately lead to placental and embryonic developmental defects.

Intervention recommendations to improve uptake of breast, cervical, and colorectal cancer screening among individuals living with serious mental illness.

PURPOSE: Few efforts have been made to inform intervention design for increasing the uptake of cancer screening in individuals living with serious mental illness (ILSMI), who have lower cancer screening rates than the general population. This qualitative study explored ILSMI's and their care team member's (CTM) recommendations on the design of a breast, colorectal, and cervical cancer screening intervention for ILSMI. METHODS: Twenty-five ILSMI (mean age: 71.4 years; 60% female) and 15 CTM (mean age: 45.3 years; 80% female) were recruited through purposive sampling. Semi-structured in-depth interviews were used to collect participants' intervention suggestions. Interviews were recorded, transcribed verbatim, and imported into NVivo. Content analysis and the constant comparison method were used to analyze interview data. RESULTS: ILSMI and CTMs provided several salient recommendations. ILSMI should receive disease-specific, logistical, and screening education, and primary care staff should receive education on psychopathology. Mental health providers and patient navigators should be considered as the primary interventionist. The intervention should be delivered where ILSMI receive medical or mental health services, receive community and government services, and/or via various digital media. The intervention should improve the collaboration, communication, and coordination between primary and mental health care. Findings also pointed to the implementation of trauma-informed cancer care and integrated care models comprising mental health care and primary cancer care. CONCLUSION: These findings bring the skills, knowledge, and expertise of ILSM and their care team to intervention design for increasing colorectal, breast, and cervical cancer screening in ILSMI attending an intensive outpatient program.

Interpersonal and Community-Level Influences Across the PrEP Cascade Among Young Adult Latinx Men who Have Sex with Men Living in a US-Mexico Border Region: A Qualitative Study.

Latinx men who have sex with men (MSM) are an at-risk population for new HIV diagnoses. Pre-exposure prophylaxis (PrEP) is a suite of biomedical approaches to prevent HIV infection. Latinx MSM are less likely to take PrEP compared to non-Latinx White MSM. This qualitative study identified interpersonal- and community-level barriers and facilitators of PrEP among young adult Latinx MSM. Using stratified purposeful sampling, 27 Latinx men, ages 19-29 years and living in a US-Mexico border region, completed self-report demographic surveys and participated in semi-structured in-depth interviews assessing barriers and facilitators to PrEP. Directed content analysis was used to identify both a priori and emerging themes. Most participants reported that other people, including peers, friends, partners, and health care providers were both supportive and discouraging of PrEP use. Participants' intersectional identities as members of both Latinx and LGBTQ+ (Lesbian, Gay, Bisexual, Transgender, Queer) communities both hindered and facilitated PrEP use.

Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development.

The thymus is responsible for generating a diverse yet self-tolerant pool of T cells1. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought2. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers3. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function.

Barriers and opportunities to measuring oncology patient navigation impact: Results from the National Navigation Roundtable survey.

BACKGROUND: Patient navigation improves cancer care delivery for those most at risk for poor outcomes. Lack of sustainable funding threatens the full integration of navigation services into health care delivery systems. Standardized navigation metrics that document impact and identify best practices are necessary to support sustainability. METHODS: The National Navigation Roundtable administered a web-based, cross-sectional survey to oncology patient navigation programs to identify barriers and facilitators to the use of navigation metrics. The 38-item survey asked about data-collection practices and specific navigation metrics used by the program. Exploratory and descriptive statistics were used to identify factors associated with data collection and reporting. RESULTS: Seven hundred fifty respondents from across the country represented navigation programs across the continuum of care. Although 538 respondents (72%) reported participating in routine data collection, only one-half of them used data for reporting purposes. For the 374 programs that used electronic health records, only 40% had discrete, reportable navigation fields, and 25% had an identifier for navigated patients. Program funding was identified as the only characteristic associated with data collection, whereas the type of data collected was associated with work setting, participation in alternative payment models, and where on the continuum navigation services are provided. Respondents participating in an oncology accreditation program were more likely to collect specific outcome metrics across the continuum and to use those data for reporting purposes. The most common barriers to data collection were time (55%) and lack of support for complex data systems and/or platforms (50%). CONCLUSIONS: Inconsistent data collection and reporting of oncology navigation programs remain a threat to sustainability. Aligning data collection with oncology accreditation, funding, and reimbursement is a viable path forward.

Exploring classes of cancer patient navigators and determinants of navigator role retention.

BACKGROUND: In the current nationwide study, the authors used latent class analysis (LCA) to identify classes of cancer patient navigators (CPNs) and examined whether class membership and 12 indicators were related to navigator role retention. METHODS: By using data from 460 CPNs in the United States, LCA identified classes (ie, homogenous subgroups) of CPNs with the following indicators: type of CPN (clinical vs nonclinical), education level, area(s) of the cancer care continuum in which the CPN provided patient navigation, region and urbanity where the CPN provided services, organizational work setting, and patient navigation program funding source. The associations of navigator retention with class membership and each indicator were examined using χ2 tests. RESULTS: LCA identified 3 classes of CPNs. Classes 1 and 3 were conceptualized as distinct, homogeneous subgroups of clinical CPNs that appeared to differ mainly on their likelihood of engagement in outreach, survivorship, palliative care, and end-of-life patient navigation. Class 2 was conceptualized as a nonclinical CPN subgroup that was distinct primarily based on their high endorsement of employment in programs, which are at least partially funded by grants and engagement in earlier stages of patient navigation (eg, early detection). The provision of survivorship and treatment patient navigation was related to navigator role retention, with senior CPNs providing these patient navigation services more than novice CPNs. CONCLUSIONS: The current study highlights 3 distinct classes of CPNs, provides initial information regarding determinants of navigator retention, and makes several recommendations for future patient navigation research.

Comparing clinical and nonclinical cancer patient navigators: A national study in the United States.

BACKGROUND: A nationwide survey was conducted to examine differences between clinical and nonclinical oncology navigators in their service provision, engagement in the cancer care continuum, personal characteristics, and program characteristics. METHODS: Using convenience sampling, 527 oncology navigators participated and completed an online survey. Descriptive statistics, χ2 statistics, and t tests were used to compare nonclinical (eg, community health worker) and clinical (eg, nurse navigators) navigators on the provision of various navigation services, personal characteristics, engagement in the cancer care continuum, and program characteristics. RESULTS: Most participants were clinical navigators (76.1%). Compared to nonclinical navigators, clinical navigators were more likely to have a bachelor's degree or higher (88.6% vs 69.6%, P < .001), be funded by operational budgets (84.4% vs 35.7%, P < .001), and less likely to work at a community-based organization or nonprofit (2.0% vs 36.5%, P < .001). Clinical navigators were more likely to perform basic navigation (P < .001), care coordination (P < .001), treatment support (P < .001), and clinical trial/peer support (P = .005). Clinical navigators were more likely to engage in treatment (P < .001), end-of-life (P < .001), and palliative care (P = .001) navigation. CONCLUSIONS: There is growing indication that clinical and nonclinical oncology navigators perform different functions and work in different settings. Nonclinical navigators may be more likely to face job insecurity because they work in nonprofit organizations and are primarily funded by grants.

Addressing a critical need for caregiver support in neuro-oncology: development of a caregiver navigation intervention using eSNAP social resource visualization.

Informal caregivers are key to oncology care, but often have unmet needs, leading to poor psychological and physical health outcomes. Comprehensive, proactive caregiver support programs are needed. We describe the development of a support intervention for caregivers of persons with brain tumors. The intervention uses a caregiver navigator to help participants identify and capitalize on existing social support resources captured using a web-based tool (eSNAP) and connects participants to existing formal services. We describe the iterative development process of the manualized intervention with particular focus on the caregiver navigator sessions. The process included review of the literature and published patient navigation programs, expert and stakeholder review, and study team member review. Quantitative and qualitative data were captured from the first 15 participants randomized to receive the intervention, enrolled from February 2020 to December 2020. Four participants dropped from the study, 9 completed at least 7 modules, and 8 participants completed all 8. Quantitative and qualitative data were collected primarily from those who completed the intervention; data suggest caregivers were satisfied with the intervention and found it helpful. Our intervention is one of the first theory-based caregiver support interventions to include caregiver navigation in neuro-oncology. We use best-practice guidelines for design, including extensive stakeholder feedback. COVID-19 may have impacted recruitment and participation, but some preliminary data suggest that those able to engage with the intervention find it helpful. Data collection is ongoing in a larger trial. If effective, caregiver navigation could be a model for future interventions to ensure caregiver support.

Training cancer caregiver navigators: experiences from implementing the eSNAP and caregiver navigator intervention.

Patient navigation is increasingly common in cancer care. While navigation programs often involve informal family caregivers, few navigation interventions specifically target the family caregiver. We developed the eSNAP and Caregiver Navigator Intervention to help cancer family caregivers identify and capitalize on informal and formal social support resources. While the skill set for patient navigators may be adequate for supporting caregivers, other skills and areas of knowledge expertise are needed. In addition, sparse documentation of navigator training best practices creates further challenges for dissemination and implementation. Our goal is to describe the education and training of cancer caregiver navigators within key competencies used to prepare and support navigators to deliver our manualized intervention. Nationally recognized navigation competencies, related to developing a sensitivity to ethical, cultural, and professional issues, knowledge development, skills development, and practice-based learning, were identified and adapted. Performance goals were identified within each competency. Training activities were selected to support competency development. Based on adult learning theories, we emphasize multiple learning strategies, including experiential learning and critical reflection. Two caregiver navigators engaged in initial training between December, 2019 and February, 2020. Initial training was supervised by study leadership, who coordinated with experts and stakeholders. Navigators completed initial training. We describe lessons learned. To ensure that navigators are well-equipped to provide effective services, evidence-based training programs that include navigation and protocol-specific competencies are needed. Given the lack of detailed training programs in the literature, we created a flexible, multimodal learning approach that other teams may adopt.

The psychosocial needs of underserved breast cancer survivors and perspectives of their clinicians and support providers.

PURPOSE: Breast cancer survivors (BrCS) experience many psychosocial difficulties following treatment, leading to an increased risk of psychological distress compared to the general population. This is especially true for underserved BrCS whose unmet supportive care needs can result in worse physical and mental health outcomes. This qualitative study compared healthcare and support providers' perceptions of BrCS' needs to survivors' perceptions of their own needs. METHODS: Semi-structured in-depth interviews were conducted with 25 underserved BrCS and 20 cancer survivorship stakeholders identified using purposeful sampling. Using the constant comparison method and content analysis, data were analyzed via an iterative process of coding and discussion. Data were summarized according to three intermediate and proximal themes mentioned by both stakeholders and survivors: (1) psychosocial needs of cancer survivors, (2) support, and (3) benefit finding/positive feelings about cancer. Demographic data were analyzed by calculating descriptive statistics. RESULTS: There was consistency in providers' and survivors' perceptions of post-treatment mood changes, financial burden, familial stress, and physical changes. Providers and survivors differed in perceptions of BrCS' preferred sources of care and support, effects of cancer treatment on body image, the effects of fear of cancer recurrence on follow-up care, and benefit finding. CONCLUSIONS: This study provides valuable insight into areas in which healthcare and support providers' perceptions may differ from underserved BrCS' lived experiences. Results from this study can be used to develop interventions and inform healthcare and support providers on how to provide high-quality care to underserved BrCS.

Comparing Latino Community Members' and Clinical Staff's Perspectives on Barriers and Facilitators to Colorectal Cancer Screening.

Latinos in the United States have low rates of colorectal cancer (CRC) screening even though CRC is the third leading cause of cancer death among Latinos. This qualitative study aimed to understand and compare the perspectives of clinical staff (CS) and Latino community members (LCMs) in an urban Southern California community regarding barriers and facilitators of CRC screening. Through purposive sampling, 39 LCMs (mean age: 59.4 years, 79.5% female) were recruited to participate in one of five focus groups, and 17 CS (mean age: 38.8 years, 64.7% female) were recruited to participate in semi-structured in-depth interviews, along with a demographic survey. Interviews and focus group recordings were transcribed verbatim, translated, and analyzed using direct content analysis. Demographic data were summarized using descriptive statistics. Findings suggest that CS and LCMs have both similar and opposing perspectives with regard to barriers and facilitators of CRC screening. Themes discussed included attitudes towards CRC screening, CRC knowledge, access to resources, commitments and responsibilities, social support, vicarious learning, patient-provider communication, trust, and social relationships. Study findings can be used to guide interventions and policies to improve access to CRC screening among LCMs.

Community health workers and non-clinical patient navigators: A critical COVID-19 pandemic workforce.

The COVID-19 pandemic has resulted in substantial morbidity and mortality and challenged public health agencies and healthcare systems worldwide. In the U.S., physical distancing orders and other restrictions have had severe economic and societal consequences. Populations already vulnerable in the United States have experienced worse COVID-19 health outcomes. The World Health Organization has made recommendations to engage at risk populations and communicate accurate information about risk and prevention; to conduct contract tracing; and to support those affected by COVID-19. This Commentary highlights the ways in which an existing and cost-effective, but underutilized workforce, community health workers and non-clinical patient navigators, should be deployed to address the COVID-19 pandemic. Community health workers and non-clinical patient navigators have skills in community engagement and health communication and are able to gain the trust of vulnerable communities. Furthermore, many community health workers and non-clinical patient navigators have skills in assisting community members with meeting basic needs and with navigating public health and healthcare systems. Members of this workforce are more than prepared to conduct contact tracing. State, local, tribal, and territorial public health agencies and healthcare systems should be collaborating with national, state, and local organizations that represent and employ CHWs/non-clinical patient navigators to determine how to better mobilize this workforce to address the COVID-19 pandemic. Furthermore, Congress, the Centers for Medicare & Medicaid Services (CMS), and individual states need to adopt policies to sustainably fund their critically needed services in the long term.

The Usefulness of Anti-acetylcholine Receptor Binding Antibody Testing in Diagnosing Ocular Myasthenia Gravis.

BACKGROUND: Anti-acetylcholine receptor antibody (AChR-Abs) testing is a safe and simple ancillary method for confirming the diagnosis of myasthenia gravis. Despite the test's high sensitivity (85%-90%) for generalized myasthenia gravis, AChR-Abs testing has been reported to have a low sensitivity 44%-66% for ocular myasthenia gravis (OMG). The aim of the study is to assess the effectiveness of AChR binding Abs testing for diagnosing OMG by evaluating the test's sensitivity, specificity, positive predictive value, and negative predictive value. METHODS: A retrospective chart review on 114 OMG suspects who presented to the emergency department of a tertiary eye center in Victoria, Australia, was completed. The patients presented with diplopia alone, ptosis alone, or the combination of diplopia and ptosis. All participants were followed up longitudinally in the neuro-ophthalmology outpatient clinics for the average of 2.8 months, where they have received AChR binding testing. The final diagnosis was only given to the patients who either were seropositive for AChR binding Abs and had a high clinical suspicion of OMG, or the patient who was seronegative for AChR binding Abs but was regarded as likely to have OMG clinically and responded to the diagnostic treatments (pyridostigmine bromide and immunosuppressant therapy). RESULTS: The sensitivity of AChR binding Abs testing in diagnosing OMG was higher (80%; 95% confidence interval [CI], 51.91%-95.67%) than previously reported (44%-66%). AChR binding Abs testing also had a high specificity (98.99%; 95% CI, 94.50%-99.97%) and positive predictive value (92.31%; 95% CI, 62.68%-98.85%). CONCLUSION: The study suggests the higher utility of the AChR binding Abs testing in diagnosing OMG due to its high sensitivity, specificity, and positive predictive value.

A randomized wait-list controlled trial of a social support intervention for caregivers of patients with primary malignant brain tumor.

BACKGROUND: Informal family caregivers constitute an important and increasingly demanding role in the cancer healthcare system. This is especially true for caregivers of patients with primary malignant brain tumors based on the rapid progression of disease, including physical and cognitive debilitation. Informal social network resources such as friends and family can provide social support to caregivers, which lowers caregiver burden and improves overall quality of life. However, barriers to obtaining needed social support exist for caregivers. To address this need, our team developed and is assessing a multi-component caregiver support intervention that uses a blend of technology and personal contact to improve caregiver social support. METHODS: We are currently conducting a prospective, longitudinal 2-group randomized controlled trial which compares caregivers who receive the intervention to a wait-list control group. Only caregivers directly receive the intervention, but the patient-caregiver dyads are enrolled so we can assess outcomes in both. The 8-week intervention consists of two components: (1) The electronic Social Network Assessment Program, a web-based tool to visualize existing social support resources and provide a tailored list of additional resources; and (2) Caregiver Navigation, including weekly phone sessions with a Caregiver Navigator to address caregiver social support needs. Outcomes are assessed by questionnaires completed by the caregiver (baseline, 4-week, 8-week) and the cancer patient (baseline, and 8-week). At 8 weeks, caregivers in the wait-list condition may opt into the intervention. Our primary outcome is caregiver well-being; we also explore patient well-being and caregiver and patient health care utilization. DISCUSSION: This protocol describes a study testing a novel social support intervention that pairs a web-based social network visualization tool and resource list (eSNAP) with personalized caregiver navigation. This intervention is responsive to a family-centered model of care and calls for clinical and research priorities focused on informal caregiving research. TRIAL REGISTRATION: clinicaltrials.gov , Registration number: NCT04268979 ; Date of registration: February 10, 2020, retrospectively registered.

Multi-level determinants to HPV vaccination among Hispanic farmworker families in Florida.

Background: HPV vaccination is the primary prevention method for HPV-related cancers, although among Hispanic populations, migrant farmworkers may experience exacerbated challenges to HPV vaccination due to intersecting political, social, and personal contexts. This study explored multi-level determinants of HPV vaccination among Hispanic migrant farmworker families.Methods: Using a community-engaged approach and guided by the socio-ecological model, Intervention Mapping, and PRECEDE-PROCEED constructs, we recruited parents who had a daughter and/or son age 9-15 years from a rural, faith-based, community organization in Florida. Three focus groups (n = 13) were conducted in Spanish and constant comparison methods were used to analyze qualitative data.Results: Micro-level determinants included moderate HPV vaccine knowledge, desire for more HPV vaccine information, concerns about HPV vaccine completion, health/preventive motivations, past experiences with the healthcare system, and parental gender roles related to health care. Macro-level determinants included facilitators (e.g. transportation services, clinics open after work hours, governmental programs) and barriers (e.g. supervisor/employment inflexibility, long clinic wait times) to accessing health care and vaccination in general (including HPV vaccination). Participants shared their preferences for future interventions that would meet the needs of this community, and discussed potential content and mechanisms for receiving HPV information, as well as what might facilitate their overall access, uptake, and completion of the HPV vaccine series.Discussion: Determinants to HPV vaccination emerged and underscore the importance of addressing the multi-level factors when designing and delivering an HPV vaccine intervention for this Hispanic migrant farmworker population. Improving HPV vaccination rates requires responding to situational and structural hardships that disproportionately impact this group. Thus, community-tailored and culturally appropriate multi-level interventions are needed, while emphasizing existing knowledge assets and preferences favorable towards HPV vaccination, with the ultimate goal of the decreasing HPV-related disparities. Findings suggest interventions must reach beyond the individual level to account for this unique population's lived experiences.

Patient Satisfaction with Navigator Interpersonal Relationship (PSN-I): item-level psychometrics using IRT analysis.

BACKGROUND: Patient navigation (PN) is a promising intervention to eliminate cancer health inequities. Patient navigators play a critical role in the navigation process. Patients' satisfaction with navigators is important in determining the effectiveness of PN programs. We applied item response theory (IRT) analysis to establish item-level psychometric properties for the Patient Satisfaction with Interpersonal Relationship with Navigators (PSN-I). METHODS: We conducted a confirmatory factor analysis (CFA) to establish unidimensionality of the 9-item PSN-I in 751 cancer patients (68% female) between 18 and 86 years old. We fitted unidimensional IRT models-unconstrained graded response model (GRM) and Rasch model-to PSN-I data, and compared model fit using likelihood ratio (LR) test and information criteria. We obtained item parameter estimates (IPEs), item category/operating characteristic curves, and item/test information curves for the better fitting model. RESULTS: CFA with diagonally weighted least squares confirmed that the one-factor model fit the data (RMSEA = 0.047, 95% CI = 0.033-0.060, and CFI ≈ 1). Responses to PSN-I items clustered into the 4th and 5th categories. We aggregated the first three response categories to provide stable parameter estimates for both IRT models. The GRM fit the data significantly better than the Rasch model (LR = 80.659, df = 8, p < 0.001). Akaike's information coefficient (6384.978 vs. 6320.319) and Bayesian information coefficient (6471.851 vs. 6443.771) were lower for the GRM. IPEs showed substantial variation in items' discriminating power (1.80-3.35) for GRM. CONCLUSIONS: This IRT analysis confirms the latent structure of the PSN-I and supports its use as a valid and reliable measure of latent satisfaction with PN.

Sleep disturbance and cancer-related fatigue symptom cluster in breast cancer patients undergoing chemotherapy.

PURPOSE: Sleep disturbance and cancer-related fatigue (CRF) are among the most commonly reported symptoms associated with breast cancer and its treatment. This study identified symptom cluster groups of breast cancer patients based on multidimensional assessment of sleep disturbance and CRF prior to and during chemotherapy. METHODS: Participants were 152 women with stage I-IIIA breast cancer. Data were collected before chemotherapy (T1) and during the final week of the fourth chemotherapy cycle (T2). Latent profile analysis was used to derive groups of patients at each timepoint who scored similarly on percent of the day/night asleep per actigraphy, the Pittsburgh Sleep Quality Index global score, and the five subscales of the Multidimensional Fatigue Symptom Inventory-Short Form. Bivariate logistic regression evaluated if sociodemographic/medical characteristics at T1 were associated with group membership at each timepoint. RESULTS: Three groups (Fatigued with sleep complaints, Average, Minimal symptoms) were identified at T1, and five groups (Severely fatigued with poor sleep, Emotionally fatigued with average sleep, Physically fatigued with average sleep, Average, Minimal symptoms) at T2. The majority of individuals in a group characterized by more severe symptoms at T1 were also in a more severe symptom group at T2. Sociodemographic/medical variables at T1 were significantly associated with group membership at T1 and T2. CONCLUSIONS: This study identified groups of breast cancer patients with differentially severe sleep disturbance and CRF symptom profiles prior to and during chemotherapy. Identifying groups with different symptom management needs and distinguishing groups by baseline sociodemographic/medical variables can identify patients at risk for greater symptom burden.