Evidence-based approach to mitigate cumulative stress in pediatric nurses through the development of respite rooms.

BACKGROUND: The cumulative stress toll on nurses increased during the COVID-19 pandemic. An evidence-based practice (EBP) project was conducted to understand what is known about the impacts of cumulative stress within nursing and if there are ways to mitigate stress during a nurse's shift. AIM/IMPLEMENTATION: A project team from three clinical units completed an extensive literature review and identified the need to promote detachment while supporting parasympathetic recovery. Based on this review, leaders from three pediatric clinical units (neonatal intensive care unit, cardiovascular intensive care unit, and acute pulmonary floor) implemented respite rooms. OUTCOMES: Follow-up outcomes showed a statistically significant stress reduction. For all shifts combined, the Wilcoxon Signed-Rank Test revealed that perceived stress scores from an 11-point Likert scale (0 = no stress and 10 = maximum perceived stress) were significantly lower in the post-respite room (Md = 3, n = 68) compared to in the pre-respite room (Md = 6, n = 68), Z = -7.059, p < .001, with a large effect size, r = .605. Nurses and other staff frequently utilized respite rooms during shifts. IMPLICATIONS FOR PRACTICE: Clinical inquiry and evidence-based practice processes can mitigate cumulative stress and support staff wellbeing. Respite rooms within the hospital can promote a healthy work environment among nurses and promote a self-care culture change. Evidence-based strategies to mitigate cumulative stress using respite rooms are a best practice to promote nurse wellbeing and mitigate cumulative stress.

Ketamine use for management of vaso-occlusive pain in pediatric sickle cell disease.

BACKGROUND: Typical sickle cell disease (SCD) vaso-occlusive pain episode (VOE) management includes opioids, which are often inadequate and can be associated with significant side effects. Ketamine, a dissociative anesthetic, is a potentially effective adjunct to VOE management. OBJECTIVES: This study aimed to characterize ketamine use for VOE management in pediatric SCD. METHOD: This retrospective case series summarizes a single-center experience regarding the use of ketamine for inpatient management of pediatric VOE in 156 admissions from 2014 to 2020. RESULTS: Continuous low-dose ketamine infusion was most commonly prescribed to adolescents and young adults as an adjunct to opioids (median starting dose 2.0 µg/kg/min; median maximum dose 3.0 µg/kg/min). Ketamine was started a median of 13.7 hours after admission. Median ketamine infusion duration was 3 days. In most encounters, ketamine infusion was discontinued prior to opioid patient-controlled analgesia (PCA) discontinuation. The majority of encounters (79.3%) had a reduction in either PCA dose, continuous opioid infusion, or both while receiving ketamine. Low-dose ketamine infusion was associated with side effects noted in 21.8% (n = 34) of encounters. The most common side effects included dizziness (5.6%), hallucinations (5.1%), dissociation (2.6%), and sedation (1.9%). There were no reports of ketamine withdrawal. Most patients who received ketamine went on to receive it again during a subsequent admission. CONCLUSION: Further study is needed to determine the optimal timing of ketamine initiation and dosing. The variability of ketamine administration highlights the need for standardized protocols for ketamine use in VOE management.

Multiple Signals in the Gut Contract the Mouse Norovirus Capsid To Block Antibody Binding While Enhancing Receptor Affinity.

Human norovirus is the leading cause of gastroenteritis worldwide, with no approved vaccine or antiviral treatment to mitigate infection. These plus-strand RNA viruses have T = 3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers, to which antibodies and cellular receptors bind. We previously demonstrated that bile binding to the capsid of mouse norovirus (MNV) causes several major conformational changes; the entire P domain rotates by ∼90° and contracts onto the shell, the P domain dimers rotate about each other, and the structural equilibrium of the epitopes at the top of the P domain shifts toward the closed conformation, which favors receptor binding while blocking antibody binding. Here, we demonstrate that MNV undergoes reversible conformational changes at pH 5.0 that are nearly identical to those observed when bile binds. Notably, at low pH or when metals bind, a cluster of acidic resides in the G'-H' loop interact and distort the G'-H' loop, and this may drive C'-D' loop movement toward the closed conformation. Enzyme-linked immunosorbent assays with infectious virus particles at low pH or in the presence of metals demonstrated that all tested antibodies do not bind to this contracted form, akin to what was observed with the MNV-bile complex. Therefore, low pH, cationic metals, and bile salts are physiological triggers in the gut for P domain contraction and structural rearrangement, which synergistically prime the virus for receptor binding while blocking antibody binding. IMPORTANCE The protruding domains on the calicivirus capsids are recognized by cell receptors and antibodies. We demonstrated that MNV P domains are highly mobile, and bile causes contraction onto the shell surface while allosterically blocking antibody binding. We present the near-atomic cryo-electron microscopy structures of infectious MNV at pH 5.0 and pH 7.5. Surprisingly, low pH is sufficient to cause the same conformational changes as when bile binds. A cluster of acidic residues on the G'-H' loop were most likely involved in the pH effects. These residues also bound divalent cations and had the same conformation as observed here at pH 5. Binding assays demonstrated that low pH and metals block antibody binding, and thus the G'-H' loop might be driving the conformational changes. Therefore, low pH, cationic metals, and bile salts in the gut synergistically prime the virus for receptor binding while blocking antibody binding.

A Norovirus Uses Bile Salts To Escape Antibody Recognition While Enhancing Receptor Binding.

Noroviruses, members of the Caliciviridae family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. These plus-strand RNA viruses have T=3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers to which antibodies and cellular receptors bind. In the case of mouse norovirus (MNV), bile salts have been shown to enhance receptor (CD300lf) binding to the P domain. We demonstrated previously that the P domains of several genotypes are markedly flexible and "float" over the shell, but the role of this flexibility was unclear. Recently, we demonstrated that bile causes a 90° rotation and collapse of the P domain onto the shell surface. Since bile binds distally to the P-shell interface, it was not at all clear how it could cause such dramatic changes. Here, we present the near-atomic resolution cryo-electron microscopy (cryo-EM) structure of the MNV protruding domain complexed with a neutralizing Fab. On the basis of previous results, we show here that bile salts cause allosteric conformational changes in the P domain that block antibody recognition of the top of the P domain. In addition, bile causes a major rearrangement of the P domain dimers that is likely responsible for the bile-induced collapse of the P domain onto the shell. In the contracted shell conformation, antibodies to the P1 and shell domains are not expected to bind. Therefore, at the site of infection in the gut, the host's own bile allows the virus to escape antibody-mediated neutralization while enhancing cell attachment. IMPORTANCE The major feature of calicivirus capsids is the 90 protruding domains (P domains) that are the site of cell receptor attachment and antibody epitopes. We demonstrated previously that these P domains are highly mobile and that bile causes these "floating" P domains in mouse norovirus (MNV) to contract onto the shell surface. Here, we present the near-atomic cryo-EM structure of the isolated MNV P domain complexed with a neutralizing Fab fragment. Our data show that bile causes two sets of changes. First, bile causes allosteric conformational changes in the epitopes at the top of the P domain that block antibody binding. Second, bile causes the P domain dimer subunits to rotate relative to each other, causing a contraction of the P domain that buries epitopes at the base of the P and shell domains. Taken together, the results show that MNV uses the host's own metabolites to enhance cell receptor binding while simultaneously blocking antibody recognition.

Exploring health behaviors and the feasibility of a lifestyle intervention for patients with multiple myeloma.

PURPOSE: Multiple myeloma (MM) is the second most common hematologic malignancy in the USA, with higher rates observed in older adults and African Americans (AA). Survivors experience fatigue, bone pain, reduced functioning, and obesity, highlighting the value of developing lifestyle interventions for this diverse group. This study explores lifestyle behaviors and supportive care needs to inform future programs tailored to the MM community. METHODS: MM survivors, ≥ 100 days post autologous stem cell transplant (ASCT) with a BMI ≥ 20 kg/m2, were recruited from two university hospitals. Diet, physical activity, and quality of life (QOL) were measured using validated measures. Qualitative interviews gathered information on survivorship needs and interests related to supportive interventions. Quantitative data was analyzed using descriptive statistics; qualitative data were analyzed using deductive strategies. RESULTS: Seveny-two MM survivors participated (65% white, 35% black). Participants were 62.5 ± 15.8 years of age. Fifty percent were classified as obese and 65% were insufficiently active. Participants reported diets high in added sugars and saturated fats. QOL measures indicated clinically significant challenges in physical and sexual function. Most (87%) were interested in a lifestyle program. Predominant themes regarding survivors' desires for a lifestyle program included social support, guided exercise, meal preparation support, and disease management information. CONCLUSION: This study demonstrates the need for and interest in lifestyle change support among a racially diverse sample of MM survivors. Interventions that are group-based, target knowledge gaps, social connections, accountability, and provide structured framework with professional instruction will best address the needs of this survivor population.

Total shoulder arthroplasty using an inlay glenoid component for glenoid deficiency: mid- to long-term follow-up of a previously published cohort.

BACKGROUND: The short-term results of total shoulder arthroplasty with an inlay glenoid component performed by a single surgeon in patients with glenoid bone loss have previously been reported. The purpose of this study was to investigate the mid- to long-term clinical and radiographic outcomes of these patients. METHODS: We identified a cohort of patients who underwent total shoulder arthroplasty with an inlay glenoid component performed by a single surgeon between 2010 and 2019 for severe glenoid dysplasia and/or glenoid bone loss. Patients with a minimum of 2 years' follow-up were evaluated regarding preoperative and postoperative range of motion, radiographic findings, visual analog scale pain scores, and Single Assessment Numeric Evaluation scores. RESULTS: Overall, 39 shoulders in 33 patients were treated with an inlay glenoid component for severe glenoid bone loss. Four patients were lost to follow-up, and 1 patient died with a well-functioning implant in place. The final cohort included 34 shoulders in 28 patients (46.4% female patients [13 of 28] and 53.6% male patients [15 of 28]) with a mean age of 66.9 years (range, 58-81 years) and mean follow-up period of 68.3 months. Of the 34 cases, 5 were revision cases. One patient died following 2-year follow-up. Of the shoulders, 10 were classified as Walch type A2, 4 were classified as Walch type B3, and 15 were classified as Walch type C; 5 shoulders were unable to be classified. We observed statistically significant increases in range of motion (forward elevation, 38.1° [P < .001]; external rotation, 18.8° [P < .001]) and improvement in the Single Assessment Numeric Evaluation score (from 26.6 to 81.0, P < .001). Two patients underwent conversion to reverse shoulder arthroplasty at 2.2 and 1.7 years postoperatively. CONCLUSION: Inlay glenoid components provide a low rate of revision and improved clinical and functional outcomes at mid- to long-term follow-up.

Enhancing the Adoption of Evidence-Based Health Marketing and Promotion Strategies in Local Communities: Building a Communication Dissemination and Support System for the National Diabetes Prevention Program.

The Centers for Disease Control and Prevention (CDC) created a health communication marketing and promotion support system (support system) to help 10 CDC-funded national organizations (recipients) grow enrollment of underserved populations in the National Diabetes Prevention Program. This article describes the creation of a successful support system to increase the use of effective marketing approaches and key messaging. The support system was developed using a systematic approach. It included a needs assessment, audience research, marketing strategy identification, expert panel review, materials development, and dissemination guidance. Hands-on, individualized, and group end-user training and technical assistance was also included. Recipients received culturally and linguistically tailored marketing materials to support their specific priority audiences, as well as corresponding training on recommended dissemination methods. In in-depth key-informant interviews, staff from six recipients reported increased knowledge of local communities and audiences, efficacy and skills to conduct media interviews, capacity to identify and train champions and influencers, and greater community partner investments. With marketing support, 90% of recipients reported increased enrollment, of which 40% exceeded self-set targets and another 40% doubled or tripled their enrollment numbers. These findings indicate that a customized strategic health communication marketing and promotion support system presents a significant opportunity to help recipients increase enrollment in evidence-based interventions. Practitioners disseminating evidence-based interventions may consider a support system to increase program uptake.

Bile Salts Alter the Mouse Norovirus Capsid Conformation: Possible Implications for Cell Attachment and Immune Evasion.

Caliciviruses are single-stranded RNA viruses with 180 copies of capsid protein comprising the T=3 icosahedral capsids. The main capsid feature is a pronounced protruding (P) domain dimer formed by adjacent subunits on the icosahedral surface while the shell domain forms a tight icosahedral sphere around the genome. While the P domain in the crystal structure of human Norwalk virus (genotype I.1) was tightly associated with the shell surface, the cryo-electron microscopy (cryo-EM) structures of several members of the Caliciviridae family (mouse norovirus [MNV], rabbit hemorrhagic disease virus, and human norovirus genotype II.10) revealed a "floating" P domain that hovers above the shell by nearly 10 to 15 Å in physiological buffers. Since this unusual feature is shared among, and unique to, the Caliciviridae, it suggests an important biological role. Recently, we demonstrated that bile salts enhance cell attachment to the target cell and increase the intrinsic affinity between the P domain and receptor. Presented here are the cryo-EM structures of MNV-1 in the presence of bile salts (∼3 Å) and the receptor CD300lf (∼8 Å). Surprisingly, bile salts cause the rotation and contraction of the P domain onto the shell surface. This both stabilizes the P domain and appears to allow for a higher degree of saturation of receptor onto the virus. Together, these results suggest that, as the virus moves into the gut and the associated high concentrations of bile, the entire capsid face undergoes a conformational change to optimize receptor avidity while the P domain itself undergoes smaller conformational changes to improve receptor affinity.IMPORTANCE Mouse norovirus and several other members of the Caliciviridae have been shown to have a highly unusual structure with the receptor binding protruding (P) domain only loosely tethered to the main capsid shell. Recent studies demonstrated that bile salts enhance the intrinsic P domain/receptor affinity and is necessary for cell attachment. Presented here are the high-resolution cryo-EM structures of apo MNV, MNV/bile salt, and MNV/bile salt/receptor. Bile salts cause a 90° rotation and collapse of the P domain onto the shell surface that may increase the number of available receptor binding sites. Therefore, bile salts appear to be having several effects on MNV. Bile salts shift the structural equilibrium of the P domain toward a form that binds the receptor and away from one that binds antibody. They may also cause the entire P domain to optimize receptor binding while burying a number of potential epitopes.

Frequency and clinical outcomes of CYP2C19 genotype-guided escalation and de-escalation of antiplatelet therapy in a real-world clinical setting.

PURPOSE: To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI). METHODS: The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and de-escalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one year was evaluated. RESULTS: Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event compared with those escalated to prasugrel/ticagrelor (52 vs. 19 events/100 patient-years; adjusted hazard ratio [HR] 2.89 [1.44-6.13], p = 0.003). Patients without a nonfunctional allele de-escalated to clopidogrel had no difference in risk compared with those initiated and continued on prasugrel/ticagrelor (21 vs. 19 events/100 patient-years; adjusted HR 1.13 [0.51-2.34], p = 0.751). CONCLUSION: CYP2C19-guided escalation and de-escalation is common in a real-world setting. Continuation of clopidogrel in nonfunctional allele carriers is associated with adverse outcomes. De-escalation to clopidogrel in patients without a nonfunctional allele appears safe and warrants prospective study.

Clinical Utility of CYP2C19 Genotyping to Guide Antiplatelet Therapy in Patients With an Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

Current guidelines recommend dual antiplatelet therapy-a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin-for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y12 inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy. Emerging results from registry studies and small clinical trials of CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention offer new insight and contribute to a growing evidence base that supports the clinical utility of a genotyping strategy to personalize antiplatelet therapy selection.

Self-Regulation Mitigates the Association between Household Chaos and Children's Behavior Problems.

Given the potential negative effects that early childhood behavioral problems have on later development, it is important to elucidate risk and protective factors. This study examined household chaos as a predictor of externalizing and internalizing problems among young children from low-income families. Additionally, self-regulation was examined as a moderator of the association between chaos and behavior problems. One hundred young adult mother-toddler dyads participated. Moderation analyses indicated that self-regulation buffered the association between household chaos and child behavior problems. Specifically, greater household chaos was associated with more behavior problems, but only among children with poorer self-regulation. Notably, this pattern was observed for both externalizing and internalizing problems. These findings suggest that early interventions targeting young children's self-regulation skills could help prevent behavior problems among children living in chaotic home environments.

Total shoulder arthroplasty using an inlay mini-glenoid component for glenoid deficiency: a 2-year follow-up of 9 shoulders in 7 patients.

BACKGROUND: Glenoid bone loss and severe retroversion can pose difficulties when implanting a glenoid component for total shoulder arthroplasty for primary osteoarthritis. Mini-glenoid implants may be useful in the setting of severe glenoid wear in which a standard pegged glenoid component cannot be placed. MATERIALS AND METHODS: This study is a retrospective review, performed over a 3-year period, of patients who received a total shoulder arthroplasty using an inset mini-glenoid in the setting of severe glenoid dysplasia and/or medial glenoid bone loss. We identified patients with a minimum of 2 years' follow-up and evaluated preoperative and postoperative range of motion, visual analog scale scores, Single Assessment Numeric Evaluation scores, complications, and patient satisfaction. RESULTS: Seven patients (4 female and 3 male patients; 9 shoulders) with a mean age of 66 years were treated with the described procedure and had a mean follow-up of 34 months. There were 6 primary arthroplasties and 3 revision cases. Four shoulders were classified as Walch type A2 glenoids, 2 were classified as Walch type C, and 3 were unable to be classified. There was a statistically significant increase in range of motion (forward elevation, 48°; external rotation, 14°), decrease in pain scores (8 points to 1 point), and improvement in Single Assessment Numeric Evaluation scores (31.7% to 89.4%). The mean patient satisfaction score was 8.6 points on a 10-point scale. CONCLUSION: At 2-year follow-up, total shoulder arthroplasty with a mini-glenoid component can offer adequate pain relief and functional results in the setting of glenoid bone loss or severe retroversion.

Rotator cuff biology and biomechanics: a review of normal and pathological conditions.

The glenohumeral joint is a complex anatomic structure commonly affected by injury such as tendinopathy and rotator cuff tears. This review presents an up-to-date overview of research on tendon biology and structure, shoulder joint motion and stability, tendon healing, and current and potential future repair strategies. Recent studies have provided information demonstrating the serious impact on uninjured tissues after a rotator cuff tear or other cause of altered shoulder joint mechanics. Another major focus of recent research is biological augmentation of rotator cuff repair with the goal of successfully reinstating normal tendon-to-bone structure. To effectively treat shoulder pathologies, clinicians need to understand normal tendon biology, the healing process and environment, and whole shoulder stability and function.

Transplant Eligible and Ineligible Elderly Patients with AML-A Genomic Approach and Next Generation Questions.

The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies. In this review, we discuss recent modifications suggested by European Leukemia Network 2022 (ELN-2022) risk stratification and review recent aging cell biology advances with the discussion of four AML cases. While an older age, >60 years, does not constitute an absolute contraindication for allo-HCT, the careful patient selection based on a detailed and multidisciplinary risk stratification cannot be overemphasized.

Is Arthroscopic Latarjet a Cost-Effective Procedure? A Decision Analysis.

Objectives: Arthroscopic Latarjet for glenohumeral stabilization has emerged as an alternative to the open approach; however, the evidence to date has questioned if this technique delivers improved outcomes. This analysis provides an assessment of the cost and utility associated with arthroscopic versus open Latarjet. Methods: The cost-effectiveness of Latarjet stabilization was modeled over a ten-year period. Institutional cases were reviewed for equipment utilization. Cost data from ambulatory surgical centers was obtained for each piece of equipment used intraoperatively. Based upon prior analyses, the operating room cost was assigned a value of $36.14 per minute. To determine effectiveness, a utility score was derived based upon prior analysis of shoulder stabilization using the EuroQol (EQ) 5D. For reoperations, a utility score of 0.01 was assigned for a single year for revision surgeries for instability and 0.5 for minor procedures. Probability of surgical outcomes and operative time for arthroscopic and open Latarjet were taken from prior studies comparing outcomes of these procedures. Decision-tree analysis utilizing these values was performed. Results: Based upon equipment and operating room costs, arthroscopic Latarjet was found to cost $2,796.87 more than the equivalent open procedure. Analysis of the utility of these procedures were 1.330 and 1.338 quality adjusted life years obtained over the modeled period for arthroscopic versus open Latarjet, respectively. For arthroscopic Latarjet to be cost-equivalent to open Latarjet, surgical time would need to be reduced to 41.5 minutes or the surgical equipment would need to be provided at no expense, while maintaining the same success rates. Conclusion: With nearly identical utility scores favoring open surgery, the added cost associated with arthroscopic Latarjet cannot be supported with available cost and utility data. To provide value, additional benefits such as decreased post-operative narcotic utilization, decreased blood loss, or lower complications of the arthroscopic approach must be demonstrated.

Neurodevelopment of Children Whose Mothers Were Randomized to Low-Dose Aspirin During Pregnancy.

OBJECTIVE: Because low-dose aspirin is now commonly prescribed in pregnancy, we sought to assess the association between early antenatal exposure and child neurodevelopment. METHODS: We performed a noninferiority, masked, neurodevelopmental follow-up study of children between age 33 and 39 months whose mothers had been randomized to daily low-dose aspirin (81 mg) or placebo between 6 0/7 and 13 6/7 weeks of gestation through 37 weeks. Neurodevelopment was assessed with the Bayley-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) and the ASQ-3 (Ages and Stages Questionnaire, 3rd Edition). The primary outcome was the Bayley-III cognitive composite score with a difference within 4 points demonstrating noninferiority. RESULTS: A total of 640 children (329 in the low-dose aspirin group, 311 in the placebo group) were evaluated between September 2021 and June 2022. The Bayley-III cognitive composite score was noninferior between the two groups (-1, adjusted mean -0.8, 95% CI, -2.2 to 0.60). Significant differences were not seen in the language composite score (difference 0.7, 95% CI, -0.8 to 2.1) or the motor composite score (difference -0.6, 95% CI, -2.5 to 1.2). The proportion of children who had any component of the Bayley-III score lower than 70 did not differ between the two groups. Similarly, the communication, gross motor, fine motor, problem-solving, and personal-social components of the ASQ-3 did not differ between groups. Maternal characteristics, delivery outcomes, breastfeeding rates, breastfeeding duration, and home environment as measured by the Family Care Indicators were similar. CONCLUSION: Antenatal low-dose aspirin exposure was not associated with altered neurodevelopmental outcomes at age 3 years. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04888377.