Gold-Thiolate Nanocluster Dynamics and Intercluster Reactions Enabled by a Machine Learned Interatomic Potential.

Monolayer protected metal clusters comprise a rich class of molecular systems and are promising candidate materials for a variety of applications. While a growing number of protected nanoclusters have been synthesized and characterized in crystalline forms, their dynamical behavior in solution, including prenucleation cluster formation, is not well understood due to limitations both in characterization and first-principles modeling techniques. Recent advancements in machine-learned interatomic potentials are rapidly enabling the study of complex interactions such as dynamical behavior and reactivity on the nanoscale. Here, we develop an Au-S-C-H atomic cluster expansion (ACE) interatomic potential for efficient and accurate molecular dynamics simulations of thiolate-protected gold nanoclusters (Aun(SCH3)m). Trained on more than 30,000 density functional theory calculations of gold nanoclusters, the interatomic potential exhibits ab initio level accuracy in energies and forces and replicates nanocluster dynamics including thermal vibration and chiral inversion. Long dynamics simulations (up to 0.1 µs time scale) reveal a mechanism explaining the thermal instability of neutral Au25(SR)18 clusters. Specifically, we observe multiple stages of isomerization of the Au25(SR)18 cluster, including a chiral isomer. Additionally, we simulate coalescence of two Au25(SR)18 clusters and observe series of clusters where the formation mechanisms are critically mediated by ligand exchange in the form of [Au-S]n rings.

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

A Quality Improvement Project to Improve After-visit Summary Patient Instructions in a Pediatric Multidisciplinary Neuromuscular Program.

Introduction: Multidisciplinary clinics aim to coordinate care between multiple specialties for children with medical complexity yet may result in information overload for caregivers. The after-visit summary (AVS) patient instruction section offers a solution by summarizing visit details and recommendations. No known studies address patient instruction optimization and integration within a multidisciplinary clinic setting. This project aimed to improve the quality of patient instructions to support better postvisit communication between caregivers and providers in a multidisciplinary pediatric neuromuscular program. Methods: A multidisciplinary stakeholder team created a key driver diagram to improve postvisit communication between caregivers and providers in the clinic. The first specific aim was to achieve an 80% completion rate of AVS patient instructions within 6 months. To do so, a standardized electronic medical record "text shortcut" was created for consistent information in each patient's instructions. Feedback on AVS from caregivers was obtained using the Family Experiences with Coordination of Care survey and open-ended interviews. This feedback informed the next specific aim: to reduce medical jargon within patient instructions by 25% over 3 months. Completion rates and jargon use were reviewed using control charts. Results: AVS patient instruction completion rates increased from a mean of 39.4%-85.0%. Provider education reduced mean jargon usage in patient instructions, from 8.2 to 3.9 jargon terms. Conclusions: Provider education and caregiver feedback helped improve patient communication by enhancing AVS compliance and diminishing medical jargon. Interventions to improve AVS patient instructions may enhance patient communication strategies for complex medical visits.

Workplace Violence Against Primary Care Clinicians: A Narrative Review.

Workplace violence (WPV) is a commonly reported occupational hazard in healthcare and its prevalence is increasing. WPV occurs in all types of practice settings, but little is known about WPV in primary care settings in the United States (US). Because primary care practice settings differ from the inpatient settings, further examination of WPV in primary care is warranted. Our objective was to summarize the available literature highlight important gaps. We conducted a search using Pubmed and OVID for US studies of WPV in US-based adult primary care practices. Studies including only pediatric populations were excluded. Due to the lack of available literature conducted in US primary care settings, we expanded our search to include international studies. We identified 70 studies of which 5 were US based. Due to the lack of significant numbers of US-based studies, we opted to conduct a narrative review of all available studies. The evidence shows that WPV is a common occurrence in primary care settings in many countries and that the majority of primary care clinicians have experienced at least some form of non-physical violence in their careers. Most of the studies conducted were cross-sectional in design and reported on both non-physical and physical forms of WPV. There was not a consistent trend between genders in experiencing the major forms of WPV, but women were consistently more likely to be subjected to sexual harassment. Potential root causes for WPV could generally be categorized as patient-level, clinician-level, clinical encounter specific, and operational root causes. While most WPV was found to be non-physical, it still had significant emotional and job-related impacts on clinicians. These troubling results highlight the need for further studies to be conducted in the US.

DNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism.

Cancer patients are commonly affected by fatigue. Herein, we sought to examine epigenetic modifications (i.e., DNA methylation) related to fatigue in peripheral blood among patients during and after treatment for head and neck cancer (HNC). Further, we determined whether these modifications were associated with gene expression and inflammatory protein markers, which we have previously linked to fatigue in HNC. This prospective, longitudinal study enrolled eligible patients with data collected at pre-radiotherapy, end of radiotherapy, and six months and one-year post-radiotherapy. Fatigue data were reported by patients using the Multidimensional Fatigue Inventory (MFI)-20. DNA methylation (Illumina MethylationEPIC) and gene expression (Applied Biosystems Clariom S) arrays and assays for seven inflammatory markers (R&D Systems multiplex) were performed. Mixed models and enrichment analyses were applied to establish the associations. A total of 386 methylation loci were associated with fatigue among 145 patients (False Discovery Rate [FDR] < 0.05). Enrichment analyses showed the involvement of genes related to immune and inflammatory responses, insulin and lipid metabolism, neuropsychological disorders, and tumors. We further identified 16 methylation-gene expression pairs (FDR < 0.05), which were linked to immune and inflammatory responses and lipid metabolism. Ninety-one percent (351) of the 386 methylation loci were also significantly associated with inflammatory markers (e.g., interleukin 6, c-reactive protein; FDR < 0.05), which further mediated the association between methylation and fatigue (FDR < 0.05). These data suggest that epigenetic modifications associated with inflammation and immunometabolism, in conjunction with relevant gene expression and protein markers, are potential targets for treating fatigue in HNC patients. The findings also merit future prospective studies in other cancer populations as well as interventional investigations.

Solubilities of Ethylene and Carbon Dioxide Gases in Lithium-Ion Battery Electrolyte.

During Li-ion battery operation, (electro)chemical side reactions occur within the cell that can promote or degrade performance. These complex reactions produce byproducts in the solid, liquid, and gas phases. Studying byproducts in these three phases can help optimize battery lifetimes. To relate the measured gas-phase byproducts to species dissolved in the liquid-phase, equilibrium proprieties such as the Henry's law constants are required. The present work implements a pressure decay experiment to determine the thermodynamic equilibrium concentrations between the gas and liquid phases for ethylene (C2H4) and carbon dioxide (CO2), which are two gases commonly produced in Li-ion batteries, with an electrolyte of 1.2 M LiPF6 in 3:7 wt/wt ethylene carbonate/ethyl methyl carbonate and 3 wt % fluoroethylene carbonate (15:25:57:3 wt % total composition). The experimentally measured pressure decay curve is fit to an analytical dissolution model and extrapolated to predict the final pressure at equilibrium. The relationship between the partial pressures and concentration of dissolved gas in electrolyte at equilibrium is then used to determine Henry's law constants of 2.0 × 104 kPa for C2H4 and k CO2 = 1.1 × 104 kPa for CO2. These values are compared to Henry's law constants predicted from density functional theory and show good agreement within a factor of 3.

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort.

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M ("Mild") included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

Development and preliminary validation of the personalized cystic fibrosis medication questionnaire (PCF-MQ).

BACKGROUND: A personalized approach to assessing medication knowledge may identify opportunities for education to support self-management of cystic fibrosis (CF). This project describes the development, scoring, and preliminary validity of the Personalized CF Medication Questionnaire (PCF-MQ), designed to assess knowledge of prescribed CF medication purpose, administration, and dose and frequency. METHODS: Participants completed the PCF-MQ, the Knowledge of Disease Management (KDM-CF), and the Cystic Fibrosis-Medication Beliefs Questionnaire (CF-MBQ). Prescribed regimens were abstracted from medical records. Eligibility criteria were age 12 years and older, diagnosed with CF, and prescribed a CF medication. Statistical analyses were conducted using R software. Spearman rho was used to test correlations between measures. RESULTS: Sixty people with CF (pwCF) were enrolled; three people reported a regimen that substantially deviated from the medical record and were excluded from the analyses. The mean (SD) age was 20.2 (7.3) years, 54 % were female, and 74 % had a FEV1pp ≥70 %. The mean (SD) PCF-MQ total score was 77.8 (12.3) and knowledge scores ranged from a low of 58.3 for levalbuterol to 100 for ivacaftor. The PCF-MQ total score correlated with the KDM total score and subscales (Spearman Rho= 0.32-0.59, p < 0.05) and was not correlated with the CF-MBQ subscales (p > 0.05)). CONCLUSIONS: The PCF-MQ was correlated with another measure of general CF knowledge, but not health beliefs; because of the small sample size, this should be considered preliminary evidence of its validity. Advantages over existing CF knowledge measures include its practicality for use to help assess pwCF's knowledge about their prescribed regimen.

Influence of the Menstrual Cycle and Training on the Performance of a Perturbed Single-Leg Squatting Task in Female Collegiate Athletes.

Background: Anterior cruciate ligament (ACL) injuries often occur when an athlete experiences an unexpected disruption, or perturbation, during sports. ACL injury rates may also be influenced by the menstrual cycle. Purpose: To determine whether training adaptations to knee control and muscle activity during a perturbed single-leg squatting (SLS) task depend on menstrual cycle phase in female athletes. Study Design: Controlled laboratory study. Methods: A total of 21 healthy female collegiate athletes (current or former [<3 years]) who competed in 9 different sports performed an SLS task in which they attempted to match their knee position (user signal) to a target signal. The protocol consisted of a 9-condition pretest, 5 sets of 3 training trials, and a 9-condition posttest. One perturbation was delivered in each condition by altering the resistance of the device. Sagittal knee control (absolute error between the target signal and user signal) was assessed using a potentiometer. Muscle activity during perturbed squat cycles was normalized to maximal activation and to corresponding muscle activity during unperturbed squat cycles (%unperturbed) within the same test condition. Athletes performed the protocol during a distinct menstrual cycle phase (early follicular [EF], late follicular [LF], midluteal [ML]). Two-way mixed analysis of variance was used to determine the effects of the menstrual cycle and training on knee control and muscle activity during task performance. Venous blood was collected for hormonal analysis, and a series of health questionnaires and anthropometric measures were also assessed to determine differences among the menstrual cycle groups. Results: After training, athletes demonstrated better knee control during the perturbed squat cycles (lower absolute error, P < .001) and greater soleus feedback responses to the perturbation (%unperturbed, P = .035). Better knee control was demonstrated in the ML phase versus the EF phase during unperturbed and perturbed squat cycles (P < .039 for both). Quadriceps activation was greater in the ML phase compared with the EF and LF phases, both immediately before and after the perturbation (P < .001 for all). Conclusion: Athletes learned to improve knee control during the perturbed performance regardless of menstrual cycle phase. The best knee control and greatest quadriceps activation during the perturbed squatting task was found in the ML phase. Clinical Relevance: These findings may correspond to a lower incidence of ACL injury in the luteal phase and alterations in exercise performance across the menstrual cycle.

Measuring data rot: An analysis of the continued availability of shared data from a Single University.

To determine where data is shared and what data is no longer available, this study analyzed data shared by researchers at a single university. 2166 supplemental data links were harvested from the university's institutional repository and web scraped using R. All links that failed to scrape or could not be tested algorithmically were tested for availability by hand. Trends in data availability by link type, age of publication, and data source were examined for patterns. Results show that researchers shared data in hundreds of places. About two-thirds of links to shared data were in the form of URLs and one-third were DOIs, with several FTP links and links directly to files. A surprising 13.4% of shared URL links pointed to a website homepage rather than a specific record on a website. After testing, 5.4% the 2166 supplemental data links were found to be no longer available. DOIs were the type of shared link that was least likely to disappear with a 1.7% loss, with URL loss at 5.9% averaged over time. Links from older publications were more likely to be unavailable, with a data disappearance rate estimated at 2.6% per year, as well as links to data hosted on journal websites. The results support best practice guidance to share data in a data repository using a permanent identifier.

Random Occurrence or Real Association? Primary Hyperparathyroidism in a Young Man With Sickle Cell Disease.

A 32-year-old man with sickle cell disease (SCD) was admitted to the hospital for sickle cell crisis, during which laboratory workup revealed primary hyperparathyroidism. His treatment regimen included hydration, calcitonin, and calcimimetics. A parathyroid nuclear scan revealed anomalous parathyroid tissue. The precise relationship between primary hyperparathyroidism (PHPT) and SCD remains incompletely understood but may involve factors such as vitamin D deficiency, elevated erythropoietin levels, and the influence of growth factors on the development of parathyroid adenomas. Furthermore, the concurrent occurrence of both PHPT and SCD at an earlier age may potentiate adverse long-term outcomes. Effective management of PHPT in SCD entails addressing hypercalcemia and treating the underlying cause of hyperparathyroidism. While a potential association between PHPT and SCD exists, further research is essential to better elucidate their interaction, prevalence, clinical presentations, and outcomes.

Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities.

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.

Gastroenterologist and surgeon perceptions of recommendations for optimal endoscopic localization of colorectal neoplasms.

National consensus recommendations have recently been developed to standardize colorectal tumour localization and documentation during colonoscopy. In this qualitative semi-structured interview study, we identified and contrast the perceived barriers and facilitators to using these new recommendations according to gastroenterologists and surgeons in a large central Canadian city. Interviews were analyzed according to the Consolidated Framework for Implementation Research (CFIR) through directed content analysis. Solutions were categorized using the Expert Recommendations for Implementing Change (ERIC) framework. Eleven gastroenterologists and ten surgeons participated. Both specialty groups felt that the new recommendations were clearly written, adequately addressed current care practice tensions, and offered a relative advantage versus existing practices. The new recommendations appeared appropriately complex, applicable to most participants, and could be trialed and adapted prior to full implementation. Major barriers included a lack of relevant external or internal organizational incentives, non-existing formal feedback processes, and a lack of individual familiarity with the evidence behind some recommendations. With application of the ERIC framework, common barriers could be addressed through accessing new funding, altering incentive structures, changing record systems, educational interventions, identifying champions, promoting adaptability, and employing audit/feedback processes. Future research is needed to test strategies for feasibility and effectiveness.

Disparities in COVID-19 vaccine intentions, testing and trusted sources by household language for children with medical complexity.

OBJECTIVES: Children with medical complexity experienced health disparities during the coronavirus disease 2019 (COVID-19) pandemic. Language may compound these disparities since people speaking languages other than English (LOE) also experienced worse COVID-19 outcomes. Our objective was to investigate associations between household language for children with medical complexity and caregiver COVID-19 vaccine intentions, testing knowledge, and trusted sources of information. METHODS: This cross-sectional survey of caregivers of children with medical complexity ages 5 to 17 years was conducted from April-June 2022. Children with medical complexity had at least 1 Complex Chronic Condition. Households were considered LOE if they reported speaking any language other than English. Multivariable logistic regression examined associations between LOE and COVID-19 vaccine intentions, interpretation of COVID-19 test results, and trusted sources of information. RESULTS: We included 1,338 caregivers of children with medical complexity (49% response rate), of which 133 (10%) had household LOE (31 total languages, 58% being Spanish). There was no association between household LOE and caregiver COVID-19 vaccine intentions. Caregivers in households with LOE had similar interpretations of positive COVID-19 test results, but significantly different interpretations of negative results. Odds of interpreting a negative test as expected (meaning the child does not have COVID-19 now or can still get the virus from others) were lower in LOE households (aOR [95% CI]: 0.56 [0.34-0.95]). Households with LOE were more likely to report trusting the US government to provide COVID-19 information (aOR [95% CI]: 1.86 [1.24-2.81]). CONCLUSION: Differences in COVID-19 test interpretations based on household language for children with medical complexity were observed and could contribute to disparities in outcomes. Opportunities for more inclusive public health messaging likely exist.

Neoadjuvant and Adjuvant Treatment for Early-Stage Resectable Non-small Cell Lung Cancer (NSCLC): Consensus Recommendations from the International Association for the Study of Lung Cancer (IASLC).

Advances in the multidisciplinary care of early-stage resectable non-small cell lung cancer (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and re-organization of care pathways. Perhaps most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the IASLC commissioned a diverse multidisciplinary international expert panel to evaluate the current landscape and provide diagnostic, staging, and therapeutic recommendations for patients with rNSCLC, with particular emphasis on patients with AJCC/UICC TNM 8th edition stage II and III disease. Using a team-based approach, we generated 19 recommendations, of which all but one achieved greater than 85% consensus amongst panel members. A public voting process was initiated, which successfully validated and provided qualitative nuance to our recommendations. Highlights include: 1) the critical importance of a multidisciplinary approach to the evaluation of patients with rNSCLC driven by shared clinical decision making of a multispecialty team of expert providers; 2) biomarker testing for rNSCLC; 3) a preference for neoadjuvant chemoimmunotherapy for stage III rNSCLC; 4) equipoise regarding the optimal management of patients with stage II between up-front surgery followed by adjuvant therapy and neoadjuvant/perioperative strategies; and 5) the robust preference for adjuvant targeted therapy for patients with rNSCLC and sensitizing EGFR and ALK tumor alterations. Our primary goals were to provide practical recommendations sensitive to the global differences in biology and resources for patients with rNSCLC, and to provide expert consensus guidance tailored to the individualized patient needs, goals, and preferences in their cancer care journey as these are areas where physicians must make daily clinical decisions in the absence of definitive data. These recommendations will continue to evolve as the treatment landscape for rNSCLC expands and more knowledge is acquired on the best therapeutic approach in specific patient and disease subgroups.

University of Pennsylvania Telehealth Research Center of Excellence.

Drawing from insights from communication science and behavioral economics, the University of Pennsylvania Telehealth Research Center of Excellence (Penn TRACE) is designing and testing telehealth strategies with the potential to transform access to care, care quality, outcomes, health equity, and health-care efficiency across the cancer care continuum, with an emphasis on understanding mechanisms of action. Penn TRACE uses lung cancer care as an exemplar model for telehealth across the care continuum, from screening to treatment to survivorship. We bring together a diverse and interdisciplinary team of international experts and incorporate rapid-cycle approaches and mixed methods evaluation in all center projects. Our initiatives include a pragmatic sequential multiple assignment randomized trial to compare the effectiveness of telehealth strategies to increase shared decision-making for lung cancer screening and 2 pilot projects to test the effectiveness of telehealth to improve cancer care, identify multilevel mechanisms of action, and lay the foundation for future pragmatic trials. Penn TRACE aims to produce new fundamental knowledge and advance telehealth science in cancer care at Penn and nationally.

Examining the Effects of Digital Stories to Address Mental Illness and Sexual and Gender Minority-Related Stigma.

INTRODUCTION: Sexual and gender minority (SGM) individuals living with mental illness often experience stigma associated with marginalized identities of sexual orientation, gender identity, and mental illness (MI). Sharing stories of lived experiences is an effective approach to reducing various forms of stigma; however, it is unclear whether stories shared by SGM living with mental illness (SGM MI) can reduce MI- and SGM-related stigma. METHODS: Using a randomized controlled trial design, participants watched digital stories of self-identified SGM individuals living with a mental illness, non-SGM individuals living with mental illness, or a control condition (TedTalks on environmental issues and growing up in China) to examine the use of representative digital stories in addressing SGM- and MI-related stigma. RESULTS: In a sample of 218 participants, digital stories of SGM MI effectively reduced MI-related stigma (personal stigma (from 33.19 to 31.90) and discrimination (from 8.33 to 7.57)), but were ineffective at reducing SGM-related personal stigma (negative attitudes toward lesbians and gay men, transphobia, or genderism; p > .05). CONCLUSION: Our study highlights the need to develop culturally adapted anti-stigma programs in collaboration with individuals with lived intersectional SGM and MI experiences.

'I need to understand so we can decide together': Difficult conversations about alopecia areata.

The management of alopecia areata (AA) in pediatric patients poses unique challenges, particularly regarding treatment discussions and decision making involving both patients and their families. This commentary presents findings from unpublished research on treatment-discontinuation discussions between AA patients and their treating providers, shedding light on the hopes, expectations, and disappointments of individuals with severe AA. The study explored patient and guardian satisfaction with these discussions, emphasizing the importance of addressing psychosocial concerns, facilitating contact with support groups, and demonstrating empathy. The role of dermatologists in conversations about treatment, prognosis, and quality of life is examined, emphasizing the need for honesty, empathy, and realistic expectations. The authors propose a patient-centered approach to initiating and guiding discussions, focusing on understanding the impact of AA on patients and their families and collaboratively deciding on treatment options. The mantra: 'I need to understand how this is affecting all of you, so we can decide together what to do next' is central to this proposed approach. Special considerations for different scenarios are discussed, highlighting the importance of individualized care and effective communication. Overall, the commentary emphasizes the significance of actively listening, acknowledging emotions, and prioritizing patient and family goals to optimize care for pediatric AA patients.

Cyclophosphamide and thiotepa increases risk of transplant-associated thrombotic microangiopathy.

BACKGROUND: Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe end organ damage, acute and long-term morbidity, and mortality. Myeloablative conditioning is a known risk factor, though specific causative agents have not been identified. We hypothesized that the combination of cyclophosphamide and thiotepa (CY+TT) is particularly toxic to the endothelium, placing patients at elevated risk for TA-TMA. METHODS: We conducted a retrospective review of pediatric and young adult patients who received conditioned autologous and allogeneic HCT between 2012 and August 2023 at UCSF Benioff Children's Hospital, San Francisco. We excluded patients undergoing gene therapy or triple tandem transplants for brain tumors. Neuroblastoma tandem transplants were classified a single transplant occurrence. High dose N-acetylcysteine (NAC) prophylaxis was incorporated into the institutional standard of care from December 2016-May 2019 and May 2022-August 2023. Defibrotide was given prophylactically to patients deemed high-risk for sinusoidal obstruction syndrome (SOS) per institutional guidelines or on clinical trial NCT#02851407 for SOS prophylaxis or NCT#03384693 for TA-TMA prophylaxis. Kaplan-Meier analysis was used to estimate the 1-year cumulative incidence of TA-TMA. Univariate analysis was performed for each of the potential risk factors of interest using log-rank tests and bivariate analysis with Cox regression models using backward selection and hazard ratios were built using all covariates with a univariate p-value <0.2 for allogeneic HCT. SPSS (v29) was used to estimate all summary statistics, cumulative incidences, and uni- and bi-variate analyses. RESULTS: A total of 558 transplants were performed with 43 patients developing TA-TMA, for a 1-year cumulative incidence of 8.6% (95% CI, 5.9-11.3%) and 7.2% (95% CI, 2.9-11.5%) in allogeneic and autologous HCTs, respectively (p=0.62). In allogeneic recipients (n=417), the 1-year cumulative incidence of TA-TMA with CY+TT as part of conditioning was 35.7% (95% CI, 15.7-55.7%) compared to 11.7% (95% CI, 7.2-16.2%) with either CY or TT alone, and 1.2% (95% CI, 0-2.8%) if neither agent was included in the conditioning regimen (p<0.001). Use of either CY or TT (HR=10.14; p=0.002) or CY+TT (HR=35.93; p<0.001), viral infections (HR=4.3; p=0.017) and fungal infections (HR=2.98; p=0.027) were significant factors resulting in increased risk for developing TA-TMA. In subjects undergoing autologous HCT (n=141), the 1-year cumulative incidence of TA-TMA with CY+TT was 19.6% (95% CI, 8.8-30.6%) while TA-TMA did not occur in patients receiving either CY or TT alone or when neither were included (p<0.001). TA-TMA occurred only in patients with neuroblastoma receiving CY+TT as part of their conditioning. For autologous patients who received CY+TT, those who were CMV seronegative at the time of HCT had an incidence of TA-TMA of 6.7% (95% CI, 0.1-15.7%) compared to 38.1% (95% CI, 35-41.2%) for those CMV seropositive (p=0.007). CONCLUSIONS: These data show that CY or TT alone or in combination as part of pre-transplant conditioning prior to HCT increase the incidence of TA-TMA. Alternative conditioning excluding the combination of CY+TT should be considered whenever possible to limit the development of TA-TMA.

Student nurses' experiences with a digital educational resource supporting learning in nursing home placements: A qualitative study.

BACKGROUND: Nursing education should improve clinical placements in nursing homes to foster and enhance student nurses' learning experiences. Initiatives for digital educational resource used to teach and supervise students to complement learning are increasingly being adopted and considered important in nursing education. However, little is known about how digital educational resources can facilitate learning in placements. Research on the value of such resources from student nurses' perspective is required. AIM: To explore first-year student nurses' experiences with a digital educational resource developed to support learning in nursing home placements. DESIGN: This study has a qualitative explorative design and is part of a larger research project in which a digital educational resource named DigiQUALinPRAX was developed. SETTINGS: This study was conducted at three publicly funded nursing homes affiliated with one Norwegian university. PARTICIPANTS: Twenty-three first-year student nurses. METHODS: Data was generated through pre- and post-placement group interviews and analysed using reflexive thematic analysis. Standards for Reporting Qualitative Research were applied in this stud. FINDINGS: One overreaching theme and three subthemes related to student nurses' experiences with a digital educational resource were identified. The digital educational resource gave a feeling of being acknowledged as a learner by (1) providing a structure and preparation that made the placement feel less overwhelming, (2) supporting professional reflection and assessment practices, and (3) facilitating collaboration when all stakeholders used the resource actively. CONCLUSIONS: This study indicates that student nurses' learning process in nursing home placements can be supported through digital educational resources customised for this learning arena. The findings indicate that the digital educational resource facilitated pre-placement preparedness, provided structure and flexibility, and enhanced reflection and assessment practices during clinical placement. However, encouraging tripartite usage is essential to exploit the full potential of digital educational resources.