Feasibility and acceptability of patient- and clinician-level antithrombotic stewardship interventions to reduce gastrointestinal bleeding risk in patients using warfarin (Anticoagulation with Enhanced Gastrointestinal Safety): a factorial randomized controlled pilot trial.

Background: Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants. Objectives: (1) Determine the feasibility of a factorial trial testing patient activation and clinician outreach to reduce gastrointestinal (GI) bleeding risk in patients prescribed warfarin-antiplatelet therapy without proton pump inhibitor gastroprotection and (2) assess intervention acceptability. Methods: Pragmatic 2 × 2 factorial cluster-randomized controlled pilot comparing (1) a patient activation booklet vs usual care and (2) clinician notification vs clinician notification plus nurse facilitation was performed. The primary feasibility outcome was percentage of patients completing a structured telephone assessment after 5 weeks. Exploratory outcomes, including effectiveness, were evaluated using chart review, surveys, and semistructured interviews. Results: Among 47 eligible patients, 35/47 (74.5%; 95% CI, 58.6%-85.7%) met the feasibility outcome. In the subset confirmed to be high risk for upper GI bleeding, 11/29 (37.9%; 95% CI, 16.9%-64.7%) made a medication change, without differences between intervention arms. In interviews, few patients reported reviewing the activation booklet; barriers included underestimating GI bleeding risk, misunderstanding the booklet's purpose, and receiving excessive health communication materials. Clinicians responded to notification messages for 24/47 patients (51.1%; 95% CI, 26.4%-75.4%), which was lower for surgeons than nonsurgeons (22.7% vs 76.0%). Medical specialists but not surgeons viewed clinician notification as acceptable. Conclusion: The proposed trial design and outcome ascertainment strategy were feasible, but the patient activation intervention is unlikely to be effective as designed. While clinician notification appears promising, it may not be acceptable to surgeons, findings which support further refinement and testing of a clinician notification intervention.

Feasibility and potential effectiveness of nurse-led video-coaching interventions for childhood, adolescent, and young adult cancer survivors: the REVIVER study.

BACKGROUND: Childhood, adolescent, and young adult (CAYA) cancer survivors, at risk for late effects, including cancer-related fatigue, cardiovascular issues, and psychosocial challenges, may benefit from interventions stimulating behaviour adjustments. Three nurse-led eHealth interventions (REVIVER) delivered via video calls and elaborating on person-centred care, cognitive behaviour therapy and/or motivational interviewing were developed. These interventions target: 1) fatigue management, 2) healthier lifestyle behaviours, and 3) self-efficacy and self-management. This study aimed to assess the feasibility and potential effectiveness of the REVIVER interventions for CAYA cancer survivors and healthcare professionals. METHODS: In a single-group mixed methods design, CAYA cancer survivors aged 16-54, more than five years post-treatment, were enrolled. Feasibility, assessed via Bowen's outcomes for feasibility studies, included acceptability, practicality, integration and implementation, demand and adherence. Qualitative data from semi-structured interviews and a focus group interview with survivors and healthcare professionals supplemented the evaluation. Paired sample t-tests assessed changes in self-reported quality of life, fatigue, lifestyle, self-management, and self-efficacy at baseline (T0), post-intervention (T1), and 6-month follow-up (T2). RESULTS: The interventions and video consults were generally acceptable, practical, and successfully integrated and implemented. Success factors included the nurse consultant (i.e., communication, approach, and attitude) and the personalised approach. Barriers included sustainability concerns, technical issues, and short intervention duration. Regarding demand, 71.4%, 65.4%, and 100% of eligible CAYA cancer survivors engaged in the fatigue (N = 15), lifestyle (N = 17) and empowerment (N = 3) intervention, respectively, with 5, 5 and 2 participants interviewed, correspondingly. Low interest (demand) in the empowerment intervention (N = 3) and dropout rates of one-third for both fatigue and empowerment interventions were noted (adherence). Improvements in quality of life, fatigue (fatigue intervention), lifestyle (lifestyle intervention), self-efficacy, and self-management were evident among survivors who completed the fatigue and lifestyle interventions, with medium and large effect sizes observed immediately after the intervention and six months post-intervention. CONCLUSIONS: Our study demonstrates the feasibility of nurse-led video coaching (REVIVER interventions) despite lower demand for the empowerment intervention and lower adherence to the fatigue and empowerment interventions. The medium and high effect sizes found for those who completed the interventions hold potential clinical significance for future studies investigating the effectiveness of the REVIVER interventions.

High-resolution spatial and spatiotemporal modelling of air pollution using fixed site and mobile monitoring in a Canadian city.

The development of high-resolution spatial and spatiotemporal models of air pollutants is essential for exposure science and epidemiological applications. While fixed-site sampling has conventionally provided input data for statistical predictive models, the evolving mobile monitoring method offers improved spatial resolution, ideal for measuring pollutants with high spatial variability such as ultrafine particles (UFP). The Quebec Air Pollution Exposure and Epidemiology (QAPEE) study measured and modelled the spatial and spatiotemporal distributions of understudied pollutants, such as UFPs, black carbon (BC), and brown carbon (BrC), along with fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in Quebec City, Canada. We conducted a combined fixed-site (NO2 and O3) and mobile monitoring (PM2.5, BC, BrC, and UFPs) campaign over 10-months. Mobile monitoring routes were monitored on a weekly basis between 8am - 10am and designed using location/allocation modelling. Seasonal fixed-site sampling campaigns captured continuous 24-hour measurements over two-week periods. Flexible Generalized Additive Models (GAMs), which combined data on pollution concentrations, spatial and spatial and temporal GIS predictors, and spatial and temporal terms, were used to model and predict concentration surfaces. Annual models for PM2.5, NO2, O3 as well as seven of the smallest size fractions in the UFP range, had high out of sample predictive accuracy (range r2: 0.54 - 0.86). Varying spatial patterns was observed across UFP size ranges measured as Particle Number Counts (PNC). The monthly spatiotemporal models for PM2.5 (r2 = 0.49), BC (r2 = 0.27), BrC (r2 = 0.29), and PNC (r2 = 0.49) had moderate or moderate-low out of sample predictive accuracy. We conducted a sensitivity analysis and found that the minimum number of 'n visits' (mobile monitoring sessions) required to model annually representative air pollution concentrations was between 24 and 32 visits dependent on the pollutant. This study provides a single source of predictive exposure models for a comprehensive set of air pollutants in Quebec City, Canada. These exposure models will feed into epidemiological research on the health impacts of ambient UFPs and other pollutants.

Associations of a toenail metal mixture with attention and memory in the Gulf long-term follow-up (GuLF) study.

BACKGROUND: Research on metal-associated neurodegeneration has largely focused on single metals. Since metal exposures typically co-occur as combinations of both toxic and essential elements, a mixtures framework is important for identifying risk and protective factors. This study examined associations between toenail levels of an eight-metal mixture and attention and memory in men living in US Gulf states. METHODS: We measured toenail concentrations of toxic (arsenic, chromium, lead, and mercury) and essential (copper, manganese, selenium, and zinc) metals in 413 non-smoking men (23-69 years, 46 % Black) from the Gulf Long-Term Follow-Up (GuLF) Study. Sustained attention and working memory were assessed at the time of toenail sample collection using the continuous performance test (CPT) and digit span test (DST), respectively. Associations between toenail metal concentrations and performance on neurobehavioral tests were characterized using co-pollutant adjusted general linear models and Bayesian Kernel Machine Regression. RESULTS: Adjusting for other metals, one interquartile range (IQR) increase in toenail chromium was associated with a 0.19 (95 % CI: -0.31, -0.07) point reduction in CPT D Prime score (poorer ability to discriminate test signals from noise). One IQR increase in toenail manganese was associated with a 0.20 (95 % CI, -0.41, 0.01) point reduction on the DST Reverse Count (fewer numbers recalled). Attention deficits were greater among Black participants compared to White participants for the same increase in toenail chromium concentrations. No evidence of synergistic interaction between metals or adverse effect of the overall metal mixture was observed for either outcome. CONCLUSIONS: Our findings support existing studies of manganese-related memory deficits and are some of the first to show chromium related attention deficits in adults. Longitudinal study of cognitive decline is needed to verify chromium findings. Research into social and chemical co-exposures is also needed to explain racial differences in metal-associated neurobehavioral deficits observed in this study.

Prognostic Value of the 2019 EULAR/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria to Renal Response One Year After Treatment in a Cohort With Childhood-Onset Lupus Nephritis.

OBJECTIVE: In 2019, the EULAR/American College of Rheumatology developed classification criteria for systemic lupus erythematosus (SLE). A positive correlation between summary score at diagnosis and SLE disease activity at five years has been noted in adult patients with lupus, but little is known among the pediatric population. We evaluated the prognostic value of higher summary scores and number of extrarenal domains at diagnosis (low/moderate number [1-5] vs high number [6-9]) to renal outcomes after one year of treatment in pediatric patients with lupus nephritis (LN). METHODS: This retrospective, single-center cohort study included 74 pediatric patients with LN. Published pediatric renal response definitions were used for our outcome measure (no, partial, and complete response). Descriptive statistics were reported, and an ordinal logistic regression estimated adjusted odds ratios (ORs) for renal response including 95% confidence intervals (CIs). RESULTS: Patients with high extrarenal domains had OR 1.47 (95% CI 0.55-2.91) of having a complete renal response compared to patients with low/moderate domains. Patients with a summary score <30 had OR 1.31 (95% CI 0.50-3.44) of having a complete renal response relative to a summary score ≥30, though a larger proportion of patients with a summary score of ≥30 had no renal response after one year of treatment. CONCLUSION: More extrarenal domains at diagnosis did not have a statistically significant impact on renal response at one year, nor did a higher summary score. However, a larger portion of patients with a summary score <30 achieved complete renal response compared to patients with a score ≥30.

Mothers' and fathers' neural responses toward gender-stereotype violations by their own children.

Gender stereotypes facilitate people's processing of social information by providing assumptions about expected behaviors and preferences. When gendered expectations are violated, people often respond negatively, both on a behavioral and neural level. Little is known about the impact of family kinship on the behavioral and neural reactions to gender-stereotype violations. Therefore, we examined whether parents show different responses when gender stereotypes are violated by their own children vs unknown children. The sample comprised 74 Dutch families with a father (Mage = 37.54), mother (Mage = 35.83), son, and daughter aged 3-6 years. Electroencephalography measurements were obtained while parents viewed pictures of their own and unknown children paired with toy or problem behavior words that violated or confirmed gender stereotypes. In half of the trials, parents evaluated the appropriateness of toy-gender and behavior-gender combinations. Parents showed stronger late positive potential amplitudes toward gender stereotype-violating behaviors by own children compared to unknown children. Moreover, parents' P1 responses toward gender stereotype-violating child behaviors were stronger for boys than for girls and for parents who evaluated gender-stereotype violations as less appropriate than gender-stereotype confirmations. These findings indicated that gender-stereotype violations by parents' own children are particularly salient and viewed as less appropriate than gender-stereotype confirmations.

The Level of Political Astuteness in Nursing Leaders: A Baseline Assessment.

OBJECTIVE: To assess the baseline knowledge of nursing leaders regarding political advocacy and healthcare policy. BACKGROUND: Although there has been considerable attention to the need for nurses' involvement in health policy, there has not been a prior assessment of the political astuteness of nursing leaders. METHODS: Researchers analyzed self-reported data from 101 nursing leaders collected via electronic survey from American Organization for Nursing Leadership members. Descriptive, correlational analysis of data assessing political astuteness and background information was completed. RESULTS: Half of the nurse leader participants demonstrated slight political astuteness. Nurse executives, including those in chief nursing officer, chief nurse executive, and vice president positions, had higher levels of political astuteness than those in nurse director and manager positions. CONCLUSION: Nursing leaders have beginning levels of political astuteness. Formal education is recommended to increase the knowledge base of nurse leaders in the areas of understanding the political and legislative process and the skills needed to advocate regarding healthcare policy, thus increasing their level of political astuteness.

Unexpected Amanita phalloides-Induced Hematotoxicity-Results from a Retrospective Study.

INTRODUCTION: Amanita phalloides poisoning is a serious health problem with a mortality rate of 10-40%. Poisonings are characterized by severe liver and kidney toxicity. The effect of Amanita phalloides poisonings on hematological parameters has not been systematically evaluated thus far. METHODS: Patients with suspected Amanita phalloides poisonings were retrospectively selected from the hospital database of the University Medical Center Groningen (UMCG). Medical data-including demographics; liver, kidney, and blood parameters; treatment; and outcomes-were collected. The severity of the poisoning was scored using the poison severity score. RESULTS: Twenty-eight patients were identified who were admitted to the UMCG with suspected Amanita phalloides poisoning between 1994 and 2022. A time-dependent decrease was observed for hemoglobin and hematocrit concentrations, leukocytes, and platelets. Six out of twenty-eight patients developed acute liver failure (ALF). Patients with ALF showed a higher increase in liver enzymes, international normalized ratios, and PSS compared to patients without ALF. Conversely, hemoglobin and platelet numbers were decreased even further in these patients. Three out of six patients with ALF died and one patient received a liver transplant. CONCLUSION: Our study shows that Amanita phalloides poisonings may be associated with hematotoxicity in patients. The quantification of hematological parameters is of relevance in intoxicated patients, especially in those with ALF.

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.

Amanita phalloides poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of Amanita poisonings. In this study, we investigated the effects of the main toxins of Amanita phalloides, α- and ß-amanitin, on hematopoietic cell viability in vitro. Hematopoietic cell lines were exposed to α-amanitin or ß-amanitin for up to 72 h with or without the pan-caspase inhibitor Z-VAD(OH)-FMK, antidotes N-acetylcysteine, silibinin, and benzylpenicillin, and organic anion-transporting polypeptide 1B3 (OATP1B3) inhibitors rifampicin and cyclosporin. Cell viability was established by trypan blue exclusion, annexin V staining, and a MTS assay. Caspase-3/7 activity was determined with Caspase-Glo assay, and cleaved caspase-3 was quantified by Western analysis. Cell number and colony-forming units were quantified after exposure to α-amanitin in primary CD34+ hematopoietic stem cells. In all cell lines, α-amanitin concentration-dependently decreased viability and mitochondrial activity. ß-Amanitin was less toxic, but still significantly reduced viability. α-Amanitin increased caspase-3/7 activity by 2.8-fold and cleaved caspase-3 by 2.3-fold. Z-VAD(OH)-FMK significantly reduced α-amanitin-induced toxicity. In CD34+ stem cells, α-amanitin decreased the number of colonies and cells. The antidotes and OATP1B3 inhibitors did not reverse α-amanitin-induced toxicity. In conclusion, α-amanitin induces apoptosis in hematopoietic cells via a caspase-dependent mechanism.

Reproductive outcomes and reproductive health care utilization among male survivors of childhood cancer: A DCCSS-LATER study.

BACKGROUND: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. RESULTS: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001). CONCLUSIONS: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists.

Keratoconus in Down syndrome: Prevalence, risk factors, severity and corneal tomographic characteristics.

BACKGROUND: This study investigated the prevalence, risk factors and severity of corneal tomographic features of keratoconus in Down syndrome (DS). Additionally, previous studies indicate anomalous corneal features in DS, without keratoconus, this study characterised corneal features in DS without keratoconus. METHODS: This prospective observational study included participants with DS ≥10 years old. Keratoconus diagnosis, risk factors and corneal tomographic characteristics were recorded. Participants underwent slit-lamp biomicroscopy, Scheimpflug corneal tomography, corneal topography and autorefraction. A diagnosis of keratoconus (DS-KC), suspect keratoconus (DS-SK) and non-keratoconus (DS-NK) was made based on expert review of scans by three fellowship trained anterior segment ophthalmologists. Corneal tomography parameters from one eye of each participant were analysed. RESULTS: Keratoconus affected 50 (26.3%) of 190 participants, diagnosed by corneal tomography, topography or slit-lamp signs. Corneal hydrops affected 14.0% of DS-KC participants. Eye rubbing was a significant risk factor for keratoconus (p = 0.036). 175 (92%) participants could undertake corneal tomography of which tomography assessment alone identified 47 (26.9%) DS-KC participants, 64 (36.6%) DS-SK participants and 64 (36.6%) DS-NK participants. Significant differences (p < 0.001) were identified when the DS-KC, DS-SK and DS-NK groups were compared in maximum keratometry and posterior elevation at the thinnest point respectively: median (interquartile range) 50.20 (10.30D), 47.60 (1.95D), 46.50 (2.40D); 24.0 (38.00 µm), 10.00 (13.75 µm), 8.00 (6.00 µm). The DS-SK and DS-NK cohorts had similar minimum pachymetry, however, had several significantly different parameters among which included greater maximum keratometry, posterior elevation at the thinnest point in the DS-SK group. CONCLUSIONS: Keratoconus is common in DS. Keratoconus screening with corneal tomography is recommended for early detection.

When intergroup contact correlates with gender-prejudice beliefs of emerging adults.

This study examined whether the contact emerging adults have with same-gender and other-gender friends, and other-gender romantic partners is associated with their sexist and gender-inequality beliefs, and whether these associations are moderated by their gender or gender contentedness (feeling content with one's gender). Dutch emerging adults (N = 381, 18-25 years old, 51% female) completed an online survey. Hierarchical multiple regression analyses revealed that more other-gender contact was associated with less gender-inequality beliefs and with less hostile sexism in people who felt less content with their gender, but with more hostile sexism in people who feel highly content with their gender. More same-gender contact was associated with more benevolent sexism and gender-inequality beliefs, as well as with men's hostile sexism. Contact with romantic partners was not associated with gender-prejudice beliefs. Thus, same-gender contact and other-gender contact with friends each are associated with gender prejudice, depending on gender and gender contentedness.

Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy.

BACKGROUND: Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization. OBJECTIVE: We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy. METHODS: We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties. RESULTS: We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma. CONCLUSIONS: Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure.

Women are expected to smile: Preliminary evidence for the role of gender in the neurophysiological processing of adult emotional faces in 3-year-old children.

Children form stereotyped expectations about the appropriateness of certain emotions for men versus women during the preschool years, based on cues from their social environments. Although ample research has examined the development of gender stereotypes in children, little is known about the neural responses that underlie the processing of gender-stereotyped emotions in children. Therefore, the current study examined whether 3-year-olds differ in the neural processing of emotional stimuli that violate gender stereotypes (i.e., male faces with fearful or happy expressions) or confirm gender stereotypes (i.e., female faces with fearful or happy expressions), and whether boys and girls differ in their neural processing of the violation and confirmation of gender stereotypes. Data from 72 3-year-olds (±6 months, 43% boy) were obtained from the YOUth Cohort Study. Electroencephalography data were obtained when children passively viewed male and female faces displaying neutral, happy, or fearful facial expressions. This study provided first indications that happy male faces elicited larger P1 amplitudes than happy female faces in preschool children, which might reflect increased attentional processing of stimuli that violate gender stereotypes. Moreover, there was preliminary evidence that girls had larger negative central (Nc) responses, associated with salience processing, toward female happy faces than male happy faces, whereas boys had larger Nc responses toward male happy faces than female happy faces. No gender differences were found in the processing of neutral and fearful facial expressions. Our results indicate that electroencephalography measurements can provide insights into preschoolers' gender-stereotype knowledge about emotions, potentially by looking at the early occipital and late fronto-central responses.