Cancer-related fatigue among patients with advanced cancer receiving immune-checkpoint inhibitors: a prospective study.

PURPOSE: The aim of this study was to determine the frequency and factors associated with severity of cancer related fatigue (CRF) as assessed by Functional Assessment of Cancer Illness Therapy-Fatigue (FACIT-F), prior to, and during 12 weeks of immune-checkpoint inhibitors (ICIs). We also explored the effects of ICIs on fatigue dimensions and interference with daily activities (Multidimensional Functional Symptom Inventory, MFSI-SF, Patient-Related Outcome Symptom Measurement Information System Short form Fatigue 7a, PROMIS F-SF), QOL (Functional Assessment of Cancer Therapy-General, FACT-G), and cancer symptoms (Edmonton Symptom Assessment Scale, ESAS). METHODS: In this prospective, longitudinal observational study, patients with a diagnosis of advanced cancer receiving ICIs were evaluated. Patient demographics, FACT-G, FACIT-F, MFSI-SF, PROMIS F-SF, and ESAS were collected prior to, and during 12 weeks of ICIs. RESULTS: A total of 160 of the 212 enrolled patients were analyzed. The median age was 61 years, 60% were female, most common cancer was melanoma (73%), and most common ICI was nivolumab 46%. The frequency of clinically significant fatigue (defined as ≤ 34/52 on FACIT-F score) was 25.6% at baseline, 25.7% at week 8, and 19.5% at week 12. There was significant improvement in FACIT-F (P = 0.016), FACT-G physical well-being (P = 0.041), FACT-G emotional well-being (P = 0.011), ESAS anxiety (P = 0.045), and ESAS psychological distress (P = 0.03) scores from baseline to week 12 of ICIs. Multivariate analysis found significant association between clinically significant CRF and PROMIS F-SF (P < 0.001) and MFSI-SF global scores (P < 0.001). CONCLUSIONS: CRF is frequent prior to the initiation of ICI treatment. Over 12 weeks of ICI treatment, CRF significantly improved. FACT-G physical well-being, FACT-G emotional well-being, ESAS anxiety, and ESAS psychological distress scores improved overtime. Further studies are needed to validate these findings.

Telehealth Preferences Among Patients With Advanced Cancer in the Post COVID-19 Vaccine Era.

BACKGROUND: Few studies have examined patient preferences for telehealth in palliative care after the availability of COVID-19 vaccines. We examined patient preferences for video versus in-person visits and factors contributing to preferences in the postvaccine era. METHODS: This is a cross-sectional survey of patients who were seen at our palliative care clinic between April 2021 and March 2022. Patients were surveyed directly their preference for either video or in-person visits for outpatient palliative care (primary outcome). We also surveyed preferences including convenience, cost, wait time, and perceptions of COVID-19 safety regarding their palliative virtual-video visit. We examined clinical factors associated with preferences with multivariate logistic regression. RESULTS: About 200 patients completed the survey. 132 (67%, 95% confidence interval [CI]: 60%, 74%) preferred virtual-video, while 16 (8%) preferred in-person visits during the COVID-19 pandemic. About 120 (61%, 95%CI: 54%, 68%) preferred virtual-video after the pandemic. Patients perceived virtual-video favorably regarding travel and related costs (179 [91%]), convenience (175 [88%]), and wait time (136 [69%]). Multivariable analysis showed concerns for catching COVID-19 from healthcare providers (odds ratio [OR]: 4.20; 95%CI: 1.24-14.25; P = 0.02) and feeling comfortable with computers or mobile devices (OR: 4.59; 95%CI: 1.02, 20.60; P = 0.047) were significantly associated with preferring virtual-video. Patients who were of Hispanic or Latino ethnicity (OR: 0.25; 95%CI: 0.09, 0.71) and had increased dypsnea (OR: 0.74; 95%CI: 0.59, 0.93) were less likely to prefer video over in-person. CONCLUSION: Patients expressed strong preference for video over in-person visits in the outpatient palliative care setting.

The urgent need for contingency management among Tribal communities in the United States: Considerations for implementation, policy, and sovereignty.

In two randomized controlled trials, culturally adapted contingency management (i.e., incentives provided for substance-negative urine samples) was associated with reduced alcohol and drug use among geographically diverse American Indian and Alaska Native (AI/AN) adults. In response to interest in contingency management from other Tribal and AI/AN communities, our research team in collaboration with AI/AN behavioral health experts, translated the research into practice with new AI/AN community partners. Tenets of community-based participatory research were applied to develop, pilot, and refine contingency management training and implementation tools, and identify implementation challenges. In partnership with the AI/AN communities, four members of the university team developed tools and identified implementation and policy strategies to increase the successful uptake of contingency management in each location. Through our collaborative work, we identified policy barriers including inadequate federal funding of contingency management incentives and a need for further clarity regarding federal anti-kickback regulations. Adoption of contingency management is feasible and can strengthen Tribal communities' capacity to deliver evidence-based substance use disorder treatments to AI/AN people. Unfortunately, non-evidence-based limits to the use of federal funding for contingency management incentives discriminate against AI/AN communities. We recommend specific federal policy reforms, as well as other practical solutions for Tribal communities interested in contingency management.

Postvaccine Era COVID-19 Pandemic-Related Distress in Palliative Care Patients With Advanced Cancer.

CONTEXT: The COVID-19 pandemic represents a source of distress in patients with advanced cancer; however, few studies have examined the extent of pandemic-related distress in the postvaccine era. OBJECTIVES: We conducted a cross-sectional survey to examine pandemic-related distress among patients seen by palliative care after vaccine availability. METHODS: Patients at our palliative care clinic were surveyed from April 2021 to March 2022 regarding 1) pandemic-related distress level, 2) potential contributors to pandemic-related distress, 3) coping strategies, 4) demographic factors and symptom burden. Univariate and multivariate analyses identified factors associated with pandemic-related distress. RESULTS: A total of 200 patients completed the survey. Of 79 (40%, 95% confidence interval [CI]: 33%, 46%) reported worse pandemic-related distress. Patients who reported greater distress were more likely to report worse social isolation (67 [86%] vs. 52 [43%]), staying home more often (75 [95%] vs. 95 [79%]), more negative experience staying at home (26 [33%] vs. 11 [9%]), worse stress with child-care duties (14 [19%] vs. 4 [3%]), less seeing family/friends (63 [81%] vs. 72 [60%]), and more difficulty traveling to medical appointments (27 [35%] vs. 20 [17%]). Thirty-seven patients (19%) reported more difficulty getting medical appointments. In multivariable analysis, younger age (odds ratio [OR], 0.97; 95% CI, 0.92-0.99; P = 0.01), worse isolation status (OR, 6.87; 95% CI, 2.76-17.12; P < 0.001), and more negative attitude towards staying home (OR, 4.49; 95% CI, 1.6-12.57; P = 0.004) were associated with pandemic-related distress. CONCLUSIONS: Patients with advanced cancer continued to experience pandemic-related distress in the postvaccine era. Our findings highlight potential opportunities to support patients.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

OBJECTIVE: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.

DR3 Regulates Intestinal Epithelial Homeostasis and Regeneration After Intestinal Barrier Injury.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) superfamily member tumor necrosis factor-like protein 1A (TL1A) has been associated with the susceptibility and severity of inflammatory bowel diseases. However, the function of the tumor necrosis factor-like protein 1A and its receptor death receptor 3 (DR3) in the development of intestinal inflammation is incompletely understood. We investigated the role of DR3 expressed by intestinal epithelial cells (IECs) during intestinal homeostasis, tissue injury, and regeneration. METHODS: Clinical phenotype and histologic inflammation were assessed in C57BL/6 (wild-type), Tl1a-/- and Dr3-/- mice in dextran sulfate sodium (DSS)-induced colitis. We generated mice with an IEC-specific deletion of DR3 (Dr3ΔIEC) and assessed intestinal inflammation and epithelial barrier repair. In vivo intestinal permeability was assessed by fluorescein isothiocyanate dextran uptake. Proliferation of IECs was analyzed by bromodeoxyuridine incorporation. Expression of DR3 messenger RNA was assessed by fluorescent in situ hybridization. Small intestinal organoids were used to determine ex vivo regenerative potential. RESULTS: Dr3-/- mice developed more severe colonic inflammation than wild-type mice in DSS-induced colitis with significantly impaired IEC regeneration. Homeostatic proliferation of IECs was increased in Dr3-/- mice, but blunted during regeneration. Cellular localization and expression of the tight junction proteins Claudin-1 and zonula occludens-1 were altered, leading to increased homeostatic intestinal permeability. Dr3ΔIEC mice recapitulated the phenotype observed in Dr3-/- mice with increased intestinal permeability and IEC proliferation under homeostatic conditions and impaired tissue repair and increased bacterial translocation during DSS-induced colitis. Impaired regenerative potential and altered zonula occludens-1 localization also were observed in Dr3ΔIEC enteroids. CONCLUSIONS: Our findings establish a novel function of DR3 in IEC homeostasis and postinjury regeneration independent of its established role in innate lymphoid cells and T-helper cells.

Effective Interventions for Nursing Student Burnout: A Scoping Review.

BACKGROUND: Burnout in nursing students negatively impacts students' health, decreases academic success, increases attrition, and threatens the quality of patient care. PURPOSE: To identify empiric research evaluating the effectiveness of interventions to prevent nursing student burnout. METHODS: This scoping review examined the PubMed, CINAHL, PsycINFO, and Google Scholar databases to identify original studies evaluating burnout interventions in nursing students. RESULTS: Of the 258 studies identified in the primary search, 208 were screened and 29 were selected for full-text review. Five quantitative reports and 1 qualitative study met the inclusion criteria. Effective interventions included recreational music-making, mindfulness-based and resilience education, integral-caring-holistic-science curriculum, Acceptance and Commitment Training, and progressive muscle relaxation. Statistically significant reductions in burnout were reported in all 5 of the quantitative studies. CONCLUSION: This review demonstrates a need for further research. Burnout interventions should be embedded in the nursing curriculum to yield a more sustainable profession.

BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis.

The intestinal immune system and microbiota are emerging as important contributors to the development of metabolic syndrome, but the role of intestinal dendritic cells (DCs) in this context is incompletely understood. BATF3 is a transcription factor essential in the development of mucosal conventional DCs type 1 (cDC1). We show that Batf3-/- mice developed metabolic syndrome and have altered localization of tight junction proteins in intestinal epithelial cells leading to increased intestinal permeability. Treatment with the glycolysis inhibitor 2-deoxy-D-glucose reduced intestinal inflammation and restored barrier function in obese Batf3-/- mice. High-fat diet further enhanced the metabolic phenotype and susceptibility to dextran sulfate sodium colitis in Batf3-/- mice. Antibiotic treatment of Batf3-/- mice prevented metabolic syndrome and impaired intestinal barrier function. Batf3-/- mice have altered IgA-coating of fecal bacteria and displayed microbial dysbiosis marked by decreased obesity protective Akkermansia muciniphila, and Bifidobacterium. Thus, BATF3 protects against metabolic syndrome and preserves intestinal epithelial barrier by maintaining beneficial microbiota.

Quality Improvement: Assessing Your Clinical Microsystem.

There is a call to action for nurses in all types of practice settings to lead change efforts that impact quality of care. An intervention may focus on an outcome or improvement of an existing process. In both instances, an understanding of organizational culture and readiness for change are needed. Evidence-based tools are available for use by nurses and interprofessional teams to assess the clinical work environment and plan for measurement of change. Learning the use of these tools is a key step in advancing quality improvement. Use of quality improvement techniques can have an immediate impact at the clinical microsystem level.

Spontaneous subarachnoid hemorrhage: a best-practice approach to identification and management in the ED.

Emergency clinicians must have a high index of suspicion and a judicious approach to evaluating the chief complaint (ie, headache) of patients with suspected subarachnoid hemorrhage, as accurate initial diagnosis and management are critical to optimizing outcomes. Aneurysmal subarachnoid hemorrhage accounts for a small percentage of strokes, but contributes significantly to the morbidity rate in stroke. The diagnosis is challenging and has devastating consequences if missed. This review evaluates the literature and current evidence, including controversies and recent guidelines, to support a best-practice approach to the diagnosis and treatment of patients with spontaneous subarachnoid hemorrhage.

Stress and depression in undergraduate students during the COVID-19 pandemic: Nursing students compared to undergraduate students in non-nursing majors.

BACKGROUND: The COVID-19 pandemic exacerbated an already alarming mental health crisis on college campuses. Nursing students were uniquely impacted through the loss of clinical practicum experiences. PURPOSE: The purpose of this study was to explore relationships between student perceptions of life-stress and depressive symptoms during the COVID-19 pandemic in nursing students compared to students in other academic disciplines. A secondary purpose of this study was to understand nursing student perceptions of how the COVID-19 pandemic impacted their educational experience. METHODS: School-related life stress and depression measures were studied in a cross-section of 2326 undergraduate students using an anonymous online survey. Follow-up qualitative data were collected (N = 12) to further explore relationships between school-related life stress and depression in nursing students. RESULTS: Nursing students had higher levels of student-life stress but fewer depressive symptoms than students in any other academic major. Students related that social support and belongingness were critical to their academic perseverance. CONCLUSIONS: Differences between nursing and non-nursing students are likely due to a multifactorial combination of social support, resilience, and posttraumatic growth.

Troubled spots: Human impacts constrain the density of an apex predator inside protected areas.

Effective conservation requires understanding the processes that determine population outcomes. Too often, we assume that protected areas conserve wild populations despite evidence that they frequently fail to do so. Without large-scale studies, however, we cannot determine what relationships are the product of localized conditions versus general patterns that inform conservation more broadly. Leopards' (Panthera pardus) basic ecology is well studied but little research has investigated anthropogenic effects on leopard density at broad scales. We investigated the drivers of leopard density among 27 diverse protected areas in northeastern South Africa to understand what conditions facilitate abundant populations. We formulated 10 working hypotheses that considered the relative influence of bottom-up biological factors and top-down anthropogenic factors on leopard density. Using camera-trap survey data, we fit a multi-session spatial capture-recapture model with inhomogenous density for each hypothesis and evaluated support using an information theoretic approach. The four supported hypotheses indicated that leopard density is primarily limited by human impacts, but that habitat suitability and management conditions also matter. The proportion of camera stations that recorded domestic animals, a proxy for the extent of human impacts and protected area effectiveness, was the only predictor variable present in all four supported models. Protected areas are the cornerstone of large felid conservation, but only when the human-wildlife interface is well managed and protected areas shelter wildlife populations from anthropogenic impacts. To ensure the long-term abundance of large carnivore populations, reserve managers should recognize the ineffectiveness of "paper parks" and promote contiguous networks of protected areas that offer leopards and other large mammal populations greater space and reduced human impacts.

Exploring digital support for the student transition to university through questionable concepts.

New students face challenges when they make the transition from school to university. Existing digital technologies used during this transition can sometimes increase the stressors associated with change. In order to explore ways forward for technology design in this space, we developed a brochure of questionable concepts. The concepts were grounded in findings of our prior research, yet were also intended to act as provocations to promote discussion in workshops involving 32 first year university students. Our analysis of workshop discussions documents the diverse issues students face around social bonding, their home environment, and their academic performance. Our findings challenge assumptions made in prior work about the ease of transition to university. We demonstrate how questionable concepts can play an important role in prompting 'safe' conversations around stressful life events for adolescents.

Significance of Serum Protein Electrophoresis in the Detection of Multiple Myeloma: A Diagnostic Interpretation of Patients with Varied Immunoglobulins.

BACKGROUND: To determine the relationship between serum protein electrophoresis (SPE) and serum immunoglobulin profiles of patients with multiple myeloma (MM). METHODS: This is a retrospective study conducted at the Eric Williams Medical Sciences Complex, focusing on patients over 18 years who received diagnostic blood tests for MM. Results for SPE and serum immunoglobulin profiles were obtained using lab logbooks. Descriptive and inferential statistics techniques were used to analyze the data. RESULTS: The median age of MM patients in Trinidad and Tobago is of 69 years. The ratio of male and female patients with the MM is 50:50. Out of 131 patients, 24 (18.32%) had M bands present, 60 (45.80%) had an increase in gamma globulin, and 16 (12.21%) had a decrease in albumin. In cases of M band presence and raised gamma, there was noticeable increase in IgG concentration and a slight increase in IgM concentration. There was also an increase in IgA concentration in patients with the M-band but a decrease in concentration in those with raised gamma. Patients with an elevated gamma had a significant increase in IgG diameter and IgG concentration. CONCLUSIONS: This study showed a relationship between the presence of M bands and serum immunoglobulins. It has proven the significance of SPE and immunoglobulins, like IgG and IGM, in the detection of MM in the early and advanced stages. Therefore, it is recommended that SPE be used, along with other laboratory tests, in the diagnosis of MM.

Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo.

Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease, modulating the location and severity of inflammation and fibrosis. TL1A expression is increased in inflamed mucosa and associated with fibrostenosing Crohn's disease. Tl1a-overexpression in mice causes spontaneous ileitis, and exacerbates induced proximal colitis and fibrosis. Intestinal fibroblasts express Death-receptor 3 (DR3; the only know receptor for TL1A) and stimulation with TL1A induces activation in vitro. However, the contribution of direct TL1A-DR3 activation on fibroblasts to fibrosis in vivo remains unknown. TL1A overexpressing naïve T cells were transferred into Rag-/- , Rag-/- mice lacking DR3 in all cell types (Rag-/-Dr3-/-), or Rag-/- mice lacking DR3 only on fibroblasts (Rag-/-Dr3∆Col1a2) to induce colitis and fibrosis, assessed by clinical disease activity index, intestinal inflammation, and collagen deposition. Rag-/- mice developed overt colitis with intestinal fibrostenosis. In contrast, Rag-/-Dr3-/- demonstrated decreased inflammation and fibrosis. Despite similar clinical disease and inflammation as Rag-/-, Rag-/-Dr3∆Col1a2 exhibited reduced intestinal fibrosis and attenuated fibroblast activation and migration. RNA-Sequencing of TL1A-stimulated fibroblasts identified Rho signal transduction as a major pathway activated by TL1A and inhibition of this pathway modulated TL1A-mediated fibroblast functions. Thus, direct TL1A signaling on fibroblasts promotes intestinal fibrosis in vivo. These results provide novel insight into profibrotic pathways mediated by TL1A paralleling its pro-inflammatory effects.

Transforming the Experience of Mirror Viewing for Individuals Faced With Disfiguring Injuries.

PURPOSE/AIMS: This study explored the feasibility of educating nurses on an emotionally sensitive topic using video. The aim was to educate nurses on how to assist individuals who have had an amputation of a limb in viewing themselves in the mirror. DESIGN: One-group repeated-measures design with 2 time points (pretest and posttest at 1 month). METHODS: Nurses viewed a video in which 8 amputee actors described how and why nurses should support individuals' viewing of self in the mirror following amputation. RESULTS: This video-based education was feasible, and recommendations were made for future research. Participants were engaged and shared insight into how this knowledge would change their nursing practice. CONCLUSIONS: A larger educational research study to test the effect of this education on improving nursing confidence and offering the mirror is recommended.