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.

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.

Evaluating the effects of age on the long-term functional outcomes following anatomic total shoulder arthroplasty.

BACKGROUND: In the past decade, the number of anatomic total shoulder arthroplasty (aTSA) procedures has steadily increased. Patients over 65 years of age comprise the vast majority of recipients, and outcomes have been well documented; however, patients are opting for definitive surgical treatment at younger ages.We aim to report on the effects of age on the long-term clinical outcomes following aTSA. METHODS: Among the patients who underwent TSA, 119 shoulders were retrospectively analyzed. Preoperative and postoperative clinical outcome data were collected. Linear regression analysis (univariate and multivariate) was conducted to evaluate the associations of clinical outcomes with age. Kaplan-Meier curves and Cox regression analyses were performed to evaluate implant survival. RESULTS: At final follow-up, patients of all ages undergoing aTSA experienced significant and sustained improvements in all primary outcome measures compared with preoperative values. Based on multivariate analysis, age at the time of surgery was a significant predictor of postoperative outcomes. Excellent implant survival was observed over the course of this study, and Cox regression survival analysis indicated age and sex to not be associated with an increased risk of implant failure. CONCLUSIONS: When controlling for sex and follow-up duration, older age was associated with significantly better patient-reported outcome measures. Despite this difference, we noted no significant effects on range of motion or implant survival. Level of evidence: IV.

Does humeral fixation technique affect long-term outcomes of total shoulder arthroplasty?

BACKGROUND: For anatomic total arthroscopic repair, cementless humeral fixation has recently gained popularity. However, few studies have compared clinical, radiographic, and patient-reported outcomes between cemented and press-fit humeral fixation, and none have performed follow-up for longer than 5 years. In this study, we compared long-term postoperative outcomes in patients receiving a cemented versus press-fit humeral stem anatomic arthroscopic repair. METHODS: This study retrospectively analyzed 169 shoulders that required primary anatomic total shoulder arthroplasty (aTSA). Shoulders were stratified by humeral stem fixation technique: cementation or press-fit. Data were collected pre- and postoperatively. Primary outcome measures included range of motion, patient reported outcomes, and radiographic measures. RESULTS: One hundred thirty-eight cemented humeral stems and 31 press-fit stems were included. Significant improvements in range of motion were seen in all aTSA patients with no significant differences between final cemented and press-fit stems (forward elevation: P=0.12, external rotation: P=0.60, and internal rotation: P=0.77). Patient reported outcome metrics also exhibited sustained improvement through final follow-up. However, at final follow-up, the press-fit stem cohort had significantly better overall scores when compared to the cemented cohort (visual analog score: P=0.04, American Shoulder and Elbow Surgeon Score: P<0.01, Simple Shoulder Test score: P=0.03). Humeral radiolucency was noted in two cemented implants and one press-fit implant. No significant differences in implant survival were observed between the two cohorts (P=0.75). CONCLUSIONS: In this series, we found that irrespective of humeral fixation technique, aTSA significantly improves shoulder function. However, within this cohort, press-fit stems provided significantly better outcomes than cemented stems in terms of patient reported outcome scores. Level of evidence: III.

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.

Pharmacogenetics of P2Y12 receptor inhibitors.

Oral P2Y12 inhibitors are commonly prescribed for cardiovascular disease and include clopidogrel, prasugrel, and ticagrelor. Each of these drugs has its strengths and weaknesses. Prasugrel and ticagrelor are more potent inhibitors of platelet aggregation and were shown to be superior to clopidogrel in preventing major adverse cardiovascular events after an acute coronary syndrome and percutaneous coronary intervention (PCI) in the absence of genotyping. However, both are associated with an increased risk for non-coronary artery bypass-related bleeding. Clopidogrel is a prodrug requiring bioactivation, primarily via the CYP2C19 enzyme. Approximately 30% of individuals have a CYP2C19 no function allele and decreased or no CYP2C19 enzyme activity. Clopidogrel-treated carriers of a CYP2C19 no function allele have decreased exposure to the clopidogrel active metabolite and lesser inhibition of platelet aggregation, which likely contributed to reduced clopidogrel efficacy in clinical trials. The pharmacogenetic data for clopidogrel are most robust in the setting of PCI, but evidence is accumulating for other indications. Guidance is available from expert consensus groups and regulatory agencies to assist with integrating genetic information into P2Y12 inhibitor prescribing decisions, and CYP2C19 genotype-guided antiplatelet therapy after PCI is one of the most common examples of clinical pharmacogenetic implementation. Herein, we review the evidence for pharmacogenetic associations with clopidogrel response and outcomes with genotype-guided P2Y12 inhibitor selection and describe guidance to assist with pharmacogenetic implementation. We also describe processes for applying genotype data for P2Y12 inhibitor therapy selection and remaining gaps in the field. Ultimately, consideration of both clinical and genetic factors may guide selection of P2Y12 inhibitor therapy that optimally balances the atherothrombotic and bleeding risks.

A Community-Based COVID-19 Vaccine Education Initiative.

Coronavirus disease 2019 (COVID-19) has had a disparate impact on Black and Latinx communities. Even before the COVID-19 pandemic, inaccessibility and distrust of the medical community rooted in historical oppression led to hesitancy about medical interventions. In Boston, COVID-19 vaccination rates of Black and Latinx adolescents lagged behind their white and Asian peers. In response, Boston Medical Center created community vaccine clinic sites across Suffolk County. Pediatric resident physicians subsequently partnered with Boston Medical Center to establish an accompanying education program entitled "Ask-a-Doc" to help improve health literacy and address vaccine hesitancy that focused on Black and Latinx adolescents. In partnership with multidisciplinary stakeholders, including Boston Public School leaders, Ask-a-Doc pediatric resident physicians staffed 46 community vaccine events in 15 zip codes. At these events, 1521 vaccine doses were administered, with most administered to Black and Latinx community members. As of January 1, 2022, 67% of 51 first-year pediatric resident physicians had participated. Ask-A-Doc is an example of a community-based intervention that directly targets health inequities and misinformation and demonstrates that pediatric resident physicians can meaningfully engage in community outreach with sufficient protected time, resources, and institutional support. The resulting connections may lead to greater trust and credibility within systematically oppressed communities.

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.

Public-Private Partnerships to Lower the Risk of Diabetes Among Black Women Using Cooperative Agreements: The National Diabetes Prevention Program and the Black Women's Health Imperative.

The National Diabetes Prevention Program (National DPP) is a partnership of public and private organizations working to build a nationwide delivery system for a lifestyle change program (LCP), which is proved to prevent or delay onset of type 2 diabetes in adults with prediabetes. Through this program, the Centers for Disease Control and Prevention (CDC) establishes partnerships with organizations to prevent or delay the onset of type 2 diabetes by using the evidence-based and audience-tailored LCP. The DP17-1705 cooperative agreement aims to expand the reach of the program in underserved areas and to populations currently underrepresented in the program relative to their risk. This article highlights a successful adaptation of the National DPP PreventT2 curriculum to address the needs of women who are Black funded by this cooperative agreement. The Change your Lifestyle, Change your Life (CYL2) program resulted from a partnership between CDC and the Black Women's Health Imperative. Successes and challenges associated with this program are highlighted. Lessons learned from these efforts can be used by practitioners to inform future type 2 diabetes prevention initiatives.

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.

Identifying Louisiana communities at the crossroads of environmental and social vulnerability, COVID-19, and asthma.

The COVID-19 pandemic has disproportionately affected the socially and environmentally vulnerable, including through indirect effects on other health conditions. Asthma is one such condition, which may be exacerbated by both prolonged adverse in-home exposures if quarantining in unhealthy homes and prolonged outdoor exposures if the ambient air quality is unhealthy or hazardous. As both are often the case in Environmental Justice (EJ) communities, here we have analyzed data at the census tract (CT) level for Louisiana to assess any correlation between social and environmental vulnerability, and health issues like COVID-19 and asthma. Higher Social Vulnerability Index (SVI), Particulate Matter less than 2.5 µm in diameter (PM2.5) and Ozone levels were associated with higher rates of cumulative COVID-19 incidence at various time points during the pandemic, as well as higher average annual asthma hospitalization rates and estimated asthma prevalence. Further, cumulative COVID-19 incidence during the first three months of the pandemic was moderately correlated with both asthma hospitalizations and estimated prevalence, suggesting similar underlying factors may be affecting both conditions. Additionally, 137 CTs were identified where social and environmental vulnerabilities co-existed, of which 75 (55%) had high estimated prevalence of asthma. These areas are likely to benefit from asthma outreach that considers both social and environmental risk factors. Fifteen out of the 137 CTs (11%) not only had higher estimated prevalence of asthma but also a high burden of COVID-19. Further research in these areas may help to elucidate any common social determinants of health that underlie both asthma and COVID-19 burdens, as well as better clarify the possible role of the environment as related to the COVID-19 burden in Louisiana.

Diabetes Self-Management Education and Association With Diabetes Self-Care and Clinical Preventive Care Practices.

PURPOSE: The purpose of the study is to assess self-reported receipt of diabetes education among people with diabetes and its association with following recommended self-care and clinical preventive care practices. METHODS: We analyzed data from the 2017 and 2018 Behavioral Risk Factor Surveillance System for 61 424 adults (≥18 years) with self-reported diabetes in 43 states and Washington, DC. Diabetes education was defined as ever taking a diabetes self-management class. The association of diabetes education with self-care practices (daily glucose testing, daily foot checks, smoking abstention, and engaging in leisure-time physical activity) and clinical practices (pneumococcal vaccination, biannual A1C test, and an annual dilated eye exam, influenza vaccination, health care visit for diabetes, and foot exam by a medical professional) was assessed. Multivariable logistic regression with predicted margins was used to predict the probability of following these practices, by diabetes education, controlling for sociodemographic factors. RESULTS: Of adults with diabetes, only half reported receiving diabetes education. Results indicate that receipt of diabetes education is associated with following self-care and clinical preventive care practices. Those who did receive diabetes education had a higher predicted probability for following all 4 self-care practices (smoking abstention, daily glucose testing, daily foot check, and engaging in leisure-time physical activity) and all 6 clinical practices (pneumonia vaccination, biannual A1C test, and an annual eye exam, flu vaccination, health care visit, and medical foot exam). CONCLUSIONS: The prevalence of adults with diabetes receiving diabetes education remains low. Increasing receipt of diabetes education may improve diabetes-related preventive care.

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.

Structural Studies on the Shapeshifting Murine Norovirus.

Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. The calicivirus capsid is composed of 180 copies of VP1 with a molecular weight of ~58 kDa. This coat protein is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. The P domain is subdivided into P1 and P2 subdomains, with the latter containing the binding sites for cellular receptors and neutralizing antibodies. Reviewed here are studies on murine norovirus (MNV) showing that the capsid responds to several physiologically relevant cues; bile, pH, Mg2+, and Ca2+. In the initial site of infection, the intestinal tract, high bile and metal concentrations and low pH cause two significant conformational changes: (1) the P domain contracts onto the shell domain and (2) several conformational changes within the P domain lead to enhanced receptor binding while blocking antibody neutralization. In contrast, the pH is neutral, and the concentrations of bile and metals are low in the serum. Under these conditions, the loops at the tip of the P domain are in the open conformation with the P domain floating on a linker or tether above the shell. This conformational state favors antibody binding but reduces interactions with the receptor. In this way, MNV uses metabolites and environmental cues in the intestine to optimize cellular attachment and escape antibody binding but presents a wholly different structure to the immune system in the serum. To our knowledge, this is the first example of a virus shapeshifting in this manner to escape the immune response.