Pregnancy in women with congenital heart disease: New insights into neonatal risk prediction.

BACKGROUND: Advances in managing adult congenital heart disease (ACHD) have led to an increased number of women with CHD reaching childbearing age. This demographic shift underscores the need for improved understanding and prediction of complications during pregnancy in this specific ACHD population. Despite progress in maternal cardiac risk assessment, the prediction of neonatal outcomes for ACHD pregnancies remains underdeveloped. Therefore, the aims of this study are to assess neonatal outcomes in a CHD women population, to identify their predictive factors and to propose a new risk score for predicting neonatal complications. METHODS: This registry study included all women born between 1975 and 1996 diagnosed with ACHD who underwent at least one cardiology consultation for ACHD in Cliniques Universitaires Saint-Luc. A multivariate analysis was performed to identify predictors of neonatal complications and these were incorporated into a new risk index. Its validity was assessed using bootstrap method. This score was then compared with scores adapted from the ZAHARA and CARPREG studies for offspring events prediction. RESULTS: Analysis of 491 pregnancies revealed 31.4% of neonatal complications. Four significant predictors of adverse neonatal outcomes were identified: cardiac treatment during pregnancy (OR 14.8, 95%CI [3.4-66]), hypertensive disorders of pregnancy (OR 11.4, 95%CI [3.4-39.0]), smoking during pregnancy (OR 10.6, 95%CI [2.8-40.6]), and pre-pregnancy BMI <18.5 kg/m² (OR 6.5, 95%CI [2.5-16.5]). The risk model demonstrated an AUC of 0.70 (95%CI [0.65-0.75]), which remained stable after bootstrap validation. This model significantly outperformed the scores adapted from ZAHARA and CARPREG data. Based on the regression coefficients, a risk score was subsequently developed comprising five risk categories. CONCLUSIONS: One third of ACHD pregnancies are complicated by poor neonatal outcome. These complications are determined by four independent factors relating to the cardiac and non-cardiac status of the patients, which have been incorporated into a risk score. Our study is one of the first to propose a predictive risk score of neonatal outcomes in ACHD pregancies, and paves the way for other validation and confirmation studies.

Hemoglobin and End-Organ Damage in Individuals with Sickle Cell Disease.

Background: Sickle cell disease (SCD) is an inherited, chronic, multifaceted blood disorder. Patients with SCD develop anemia, which has been associated with end-organ damage (EOD). Objectives: This retrospective, observational, repeated-measures study systematically characterizes the relationship between hemoglobin (Hb) level and EOD in adolescent and adult patients with SCD. Methods: The study population comprised patients with SCD aged ≥12 years with available Hb data from a US provider-centric health care database. For each patient, each Hb value over time was included as a separate observation. Study outcomes-the onset of any new EOD, including chronic kidney disease, pulmonary hypertension, stroke, and leg ulcer-were ascertained during the 1-year period after each Hb assessment. The association between Hb levels and risk of new EOD was estimated using multivariable generalized estimating equations. Results: A total of 16,043 unique patients with SCD contributed 44,913 observations. Adjusted odds of any EOD during the 1-year follow-up were significantly lower with higher Hb level. Risk reductions with higher Hb levels for chronic kidney disease, pulmonary hypertension, and leg ulcer were comparable. The risk of new EOD was significantly lower among adolescent and adult patients with higher Hb levels. Conclusions: In patients with SCD, higher Hb levels are associated with a reduced risk of developing EOD. Therapeutic strategies that result in higher Hb levels may offer clinical and economic value for patients with SCD. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Racial Diversity Among American Cardiologists: Implications for the Past, Present, and Future.

In the United States, race-based disparities in cardiovascular disease care have proven to be pervasive, deadly, and expensive. African American/Black, Hispanic/Latinx, and Native/Indigenous American individuals are at an increased risk of cardiovascular disease and are less likely to receive high-quality, evidence-based medical care as compared with their White American counterparts. Although the United States population is diverse, the cardiovascular workforce that provides its much-needed care lacks diversity. The available data show that care provided by physicians from racially diverse backgrounds is associated with better quality, both for minoritized patients and for majority patients. Not only is cardiovascular workforce diversity associated with improvements in health care quality, but racial diversity among academic teams and research scientists is linked with research quality. We outline documented barriers to achieving workforce diversity and suggest evidence-based strategies to overcome these barriers. Key strategies to enhance racial diversity in cardiology include improving recruitment and retention of racially diverse members of the cardiology workforce and focusing on cardiovascular health equity for patients. This review draws attention to academic institutions, but the implications should be considered relevant for nonacademic and community settings as well.

Differences in the prevalence of mental health disorders among Black American adults with sickle cell disease compared to those with non-heritable medical conditions or no medical conditions.

Our aim was to determine differences in the prevalence of mental health disorders between Black Americans living with sickle cell disease (SCD) and Black Americans with other, non-heritable medical conditions, or no medical conditions. We examined the prevalence of mental health disorders among a non-institutionalized, community sample of Black adults in the US from the National Survey of American Life. We compared the odds of mental health disorders between Black American adults with SCD and those with other medical conditions, or no medical condition. Among the SCD group, 38·8% reported at least one mental health disorder: 17·6% endorsed a mood disorder, 24·7% an anxiety disorder, 2·4% an eating disorder, and 11·8% a childhood disorder. Compared to those with other medical conditions, Black Americans with SCD had greater poverty, more children in the household, and were less likely to be married/cohabitating (all P < 0·05). Yet, Black Americans with SCD were not at greater odds of having a mental health disorder compared to those with other medical conditions. When compared to the group with no conditions, however, individuals with SCD had 2·57 greater odds of mood disorder (95% confidence interval: 1·43-4·65; P = 0·002). The effect remained when controlling for socioeconomic status, marital status, and perceived physical health. In this study, almost 40% of Black American adults with SCD presented with a mental health disorder. Prevalence of mental health disorders was similar among those with non-heritable medical conditions, but those without a medical condition had a lower prevalence than in SCD. Among Black Americans, there appear to be unmeasured factors, common across medical conditions, that are linked to mental health disorders.

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study.

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers. Seventeen patients received marrow from an HLA-identical sibling donor and five patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II-III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68%-98%) and 86% (95% CI, 63%-95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).

Abstract Animations for the Communication and Assessment of Pain in Adults: Cross-Sectional Feasibility Study.

BACKGROUND: Pain is the most common physical symptom requiring medical care, yet the current methods for assessing pain are sorely inadequate. Pain assessment tools can be either too simplistic or take too long to complete to be useful for point-of-care diagnosis and treatment. OBJECTIVE: The aim was to develop and test Painimation, a novel tool that uses graphic visualizations and animations instead of words or numeric scales to assess pain quality, intensity, and course. This study examines the utility of abstract animations as a measure of pain. METHODS: Painimation was evaluated in a chronic pain medicine clinic. Eligible patients were receiving treatment for pain and reported pain more days than not for at least 3 months. Using a tablet computer, participating patients completed the Painimation instrument, the McGill Pain Questionnaire (MPQ), and the PainDETECT questionnaire for neuropathic symptoms. RESULTS: Participants (N=170) completed Painimation and indicated it was useful for describing their pain (mean 4.1, SE 0.1 out of 5 on a usefulness scale), and 130 of 162 participants (80.2%) agreed or strongly agreed that they would use Painimation to communicate with their providers. Animations selected corresponded with pain adjectives endorsed on the MPQ. Further, selection of the electrifying animation was associated with self-reported neuropathic pain (r=.16, P=.03), similar to the association between neuropathic pain and PainDETECT (r=.17, P=.03). Painimation was associated with PainDETECT (r=.35, P<.001). CONCLUSIONS: Using animations may be a faster and more patient-centered method for assessing pain and is not limited by age, literacy level, or language; however, more data are needed to assess the validity of this approach. To establish the validity of using abstract animations ("painimations") for communicating and assessing pain, apps and other digital tools using painimations will need to be tested longitudinally across a larger pain population and also within specific, more homogenous pain conditions.

Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use.

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.

Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease.

Although a number of published trials exist of HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and nontransplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with SCD treated and not treated by HCT. In this brief review, projections about mortality risk based on recent published reports are reviewed and summarized. The published data show overall survival and event-free survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival rates in the Center for International Blood and Marrow Transplant Research (N = 412) and European Blood and Marrow Transplant (N = 487) registries were 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with SCD and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears to be similar to results in children. These preliminary observations, however, warrant further investigation.

Usability and Feasibility of an mHealth Intervention for Monitoring and Managing Pain Symptoms in Sickle Cell Disease: The Sickle Cell Disease Mobile Application to Record Symptoms via Technology (SMART).

Patients with sickle cell disease frequently experience severe pain events that lead to unplanned healthcare utilization. Mobile health tools (mHealth) may help prevent these events by providing remote monitoring and self-management support. This article describes the feasibility of the Sickle cell disease Mobile Application to Record symptoms via Technology (SMART), an mHealth app developed to help sickle cell disease patients monitor and manage their day-to-day symptoms. Fifteen patients recorded their pain intensity using a paper visual analog scale (VAS) and then repeated this measurement using an electronic VAS pain measure on SMART. Patients continued using SMART to record clinical symptoms, pain intensity, location and perceived severity, and treatment strategies for at least 28 days. Patient median age was 29 years (range 16-54); 60.0% were male. There was a high intraclass correlation between pain measurements entered on the paper VAS and SMART on the iPhone and the iPad We found a strong association between patient perceived pain severity and pain intensity entries using SMART (b = 1.71; p < 0.01). Daily compliance with SMART entries was a mean 75.0%, with a high of 85.7% in week 1 and low of 57.9% in week 4; however, one-third (n = 5) of the patients were 100.0% compliant even in week 4. Patients who were over age 35 or used an iPad for the study had the highest compliance rates. This study showed that SMART is a useable and feasible method for monitoring daily pain symptoms among adolescents and adults with sickle cell disease-related pain.

Factors associated with survival in a contemporary adult sickle cell disease cohort.

In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand the major contributors to early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who were enrolled since 2002 at three university hospitals in the southeast United States. Subjects were followed up for a median of 9.3 years. At enrollment, clinical parameters were collected, including hemoglobin (Hb) genotype, baseline laboratory values, comorbidities, and medication usage. Levels of soluble adhesion molecules were measured for a subset of 87 subjects. The relationship of clinical characteristics to survival was determined using regression analysis. Median age at enrollment was 32 years. Median survival was 61 years for all subjects. Median survival for Hb SS and Sß(0) was 58 years and for Hb SC and Sß(+) was 66 years. Elevated white blood count, lower estimated glomerular filtration rate, proteinuria, frequency of pain crises, pulmonary hypertension, cerebrovascular events, seizures, stroke, sVCAM-1, and short-acting narcotics use were significantly associated with decreased survival. Forty-two percent of subjects were on hydroxyurea therapy, which was not associated with survival. SCD continues to reduce life expectancy for affected individuals, particularly those with Hb Sß(0) and SS. Not only were comorbidities individually associated with decreased survival but also an additive effect was observed, thus, those with a greater number of negative endpoints had worse survival (P < 0.0001). The association of higher sVCAM-1 levels with decreased survival suggests that targeted therapies to reduce endothelial damage and inflammation may also be beneficial.

Patients welcome the Sickle Cell Disease Mobile Application to Record Symptoms via Technology (SMART).

The widespread use of mobile phones among patients provides a unique opportunity for the development of mobile health intervention designed specifically for sickle cell disease, which will improve self-management as well as health care delivery. Our objective was to determine the receptiveness of patients with sickle cell disease to technology and a mobile application (app) designed for sickle cell disease. Phase I included 100 patients who completed a survey inquiring about receptiveness to technology and use of mobile devices to self-manage and communicate with providers. Phase II surveyed 17 additional patients who tested a newly developed sickle cell disease app, to report its usability and utility. In Phase I, on a 0-10 Likert scale where 0 is not comfortable, and 10 is extremely comfortable, 87.0% of participants reported >5 comfort level using a mobile device for health care management. Participants were comfortable with texting (81.0%) and emailing (77.0%) but not with social media (40.0%). Most participants (84.0%) owned computer devices (desktops, laptops, tablets, or iPads), and 92.0% owned mobile devices. In Phase II, participants reported that the app tested was useful to track pain (88.0%), and 94.0% reported that it was easy to use, practical, and useful for health self-management. All reported that the app was useful to help one communicate with providers. Following the use of our app, patients found it an extremely valuable tool for tracking pain, health management, and communicating with providers. We conclude that mobile technology might provide an appropriate venue for sickle cell disease healthcare management.

Development of Coated PLA Films Containing a Commercial Olive Leaf Extract for the Food Packaging Sector.

A commercial olive leaf extract (OL), effective against Salmonella enterica, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, was added to three different coating formulations (methylcellulose, MC; chitosan, CT; and alginate, ALG) to produce active polylactic acid (PLA) coated films. Evaluation of these coated PLA films revealed significant inhibition of S. aureus growth, particularly with the MC and CT formulations exhibiting the highest inhibition rates (99.7%). The coated films were then tested for food contact compatibility with three food simulants (A: 10% ethanol; B: 3% acetic acid; D2: olive oil), selected to assess their suitability for pre-cut hams and ready-to-eat vegetables in relation to overall migration. However, coated films with active functions exhibited migration values in simulants A and B above legal limits, while promising results were obtained for simulant D2, highlighting the need to deeply investigate these coatings' impact on a real food system. Untargeted metabolomics revealed that the type of coating influenced the selective release of certain phenolic classes based on the food simulant tested. The Oxitest analysis of simulant D2 demonstrated that the MC and ALG-coated PLA films slightly slowed down the oxidation of this food simulant, which is an edible vegetable oil.

The use of abstract animations and a graphical body image for assessing pain outcomes among adults with sickle cell disease.

Painimation, a novel digital pain assessment tool, allows patients to communicate their pain quality, intensity, and location using abstract animations and a paintable body image. This study determined the construct validity of pain animations and body image measures by testing correlations with validated pain outcomes in adults with sickle cell disease (SCD). Analyses used baseline data from a multisite randomized trial of 359 adults with SCD and chronic pain. Participants completed questionnaires on demographics, pain severity, frequency and interference, catastrophizing, opioid use, mood and quality of life, plus the Painimation app. Participants were categorized by selected pain animations, and were split into groups based on the proportion of painted body image. The "shooting" pain animation and greater body image scores associated with poorer pain outcomes in univariate analyses, except "happy" mood days. Potential confounding was evaluated by age, gender, race, education, disability, site, depression, and anxiety. Only depression scores significantly covaried in multivariate models, accounting for the effect of greater body image score and shooting animation on all outcomes except daily pain intensity. Both pain animations and body image measures correlated with validated pain outcomes, quality of life and mental health measures. This demonstrates animations and body image data can assess SCD pain severity, potentially with more accuracy than a 0-10 scale. In exploratory analyses, depression scores accounted for the association between Painimation and other pain outcomes. Future research will explore whether Painimation can differentiate biological and psychosocial pain components. PERSPECTIVE: This article presents the preliminary construct validity of Painimation in sickle cell disease (SCD) by examining the associations of "pain animations" and body area image data with daily e-diary and traditional self-report pain outcomes.

Digital Cognitive Behavioral Therapy vs Education for Pain in Adults with Sickle Cell Disease.

Despite the significant burden of chronic pain in sickle cell disease (SCD), non-pharmacological approaches to manage pain in SCD are lacking. Behavioral interventions incorporating digital cognitive-behavioral therapy CBT) for pain should be compared to available education efforts. To compare a CBT intervention tailored for adults with SCD to a digital pain/SCD education intervention (Education) on improving pain and associated symptoms. Multisite randomized comparative effectiveness trial. Seven comprehensive SCD centers and virtual recruitment through community organizations in the United States. Adults (age 18+) with SCD-related chronic pain and/or daily opioid use randomized to CBT or Education. Over 12 weeks, the CBT arm received an app-based intervention for pain management; the Education arm received digital pain/SCD education. Both groups received interactive chatbot lessons plus personalized health coach support. Changes in pain interference scale (primary); and other patient-reported outcomes (secondary), including pain intensity, depression, anxiety, quality of life, and self-efficacy over 6 months. 453 participants completed screening, 359 (79%) were randomized to CBT (n=181) or Education (n=178), 332 (92%) were Black African American, 238 (66.3%) female. At 6 months, 250 (70%) participants (n=125 per arm) completed follow-up assessments, 93 (26%) missed their follow-up window, 16 (4%) withdrew. Engagement with the chatbot content was variable (76% connected, 48% completed ≥1 lesson). However, 80% of participants completed ≥1 session with a health coach via phone, video, or text. The 6 month change in pain interference for CBT (-2.13; 95% CI, -3.42 to -0.84) and Education (-2.66; 95%CI, -3.97 to -1.36) was not significantly different (mean difference: 0.54; 95%CI, -1.30 to 2.37; *P=*0.57). Daily pain intensity ratings did not change for either group. There were no between-arm differences in depression, anxiety, and quality of life. CBT and Education did not differ in their effect on pain and mental health in SCD when combined with health coaching. Variable engagement with digital components and high engagement with health coaching may explain the lack of between-group differences, but these findings also provide insights into delivering digital interventions in racial minority and hard-to-reach populations. Trial Registration: ClinicalTrials.gov NCT04419168.

Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.

BACKGROUND: Although nitric oxide based therapeutics have been shown in preclinical models to reduce vaso-occlusive events and improve cardiovascular function, a clinical trial of a phosphodiesterase 5 inhibitor increased rates of admission to hospital for pain. We aimed to examine if riociguat, a direct stimulator of the nitric oxide receptor soluble guanylate cyclase, causes similar increases in vaso-occlusive events. METHODS: This was a phase 1-2, randomised, double blind, placebo-controlled trial. Eligible patients were 18 years or older, had confirmed sickle cell disease documented by haemoglobin electrophoresis or HPLC fractionation (haemoglobin SS, SC, Sß-thalassemia, SD, or SO-Arab), and stage 1 hypertension or proteinuria. Participants were randomly assigned 1:1 to receive either riociguat or matching placebo via a web-based system to maintain allocation concealment. Both treatments were administered orally starting at 1·0 mg three times a day up to 2·5 mg three times a day (highest tolerated dose) for 12 weeks. Dose escalation by 0·5 mg was considered every 2 weeks if systolic blood pressure was greater than 95 mm Hg and the participant had no signs of hypotension; otherwise, the last dose was maintained. The primary outcome was the proportion of participants who had at least one adjudicated treatment-emergent serious adverse event. The analysis was performed by the intention-to-treat. This trial is registered with ClinicalTrials.gov (NCT02633397) and was completed. FINDINGS: Between April 11, 2017, and Dec 31, 2021, 165 participants were screened and consented to be enrolled into the study. Of these, 130 participants were randomly assigned to either riociguat (n=66) or placebo (n=64). The proportion of participants with at least one treatment-emergent serious adverse event was 22·7% (n=15) in the riociguat group and 31·3% (n=20) in the placebo group (difference -8·5% [90% CI -21·4 to 4·5]; p=0·19). A similar pattern emerged in other key safety outcomes, sickle cell related vaso-occlusive events (16·7 [n=11] vs 21·9% [n=14]; difference -5·2% [-17·2 to 6·5]; p=0·42), mean pain severity (3·18 vs 3·32; adjusted mean difference -0·14 [-0·70 to 0·42]; p=0·69), and pain interference (3·15 vs 3·12; 0·04 [-0·62 to 0·69]; p=0·93) at 12 weeks were similar between groups. Regarding the key clinical efficacy endpoints, participants taking riociguat had a blood pressure of -8·20 mm Hg (-10·48 to -5·91) compared with -1·24 (-3·58 to 1·10) in those taking placebo (-6·96 mm Hg (90% CI -10·22 to -3·69; p<0·001). INTERPRETATION: Riociguat was safe and had a significant haemodynamic effect on systemic blood pressure. The results of this study provide measures of effect and variability that will inform power calculations for future trials. FUNDING: Bayer Pharmaceuticals.

Association between trauma triage and time-to-vaso-occlusive events in patients with sickle cell disease after traumatic injury: a retrospective study.

Introduction: Sickle cell disease (SCD) is associated with vaso-occlusive events (VOEs) that can lead to disease complications, including early mortality. Given that similar inflammatory responses characterize VOE and traumatic injury, injured patients with SCD may be vulnerable to acute complications. This study is the first to examine whether traumatic injury is associated with increased severity of future VOEs. Methods: This cohort study was conducted using electronic health record data from an SCD clinic in Western Pennsylvania; 356 patients with SCD from January 2000 to July 2021 were identified via retrospective chart review. 55 patients were eligible based on continuous medical record data spanning 1 year preinjury and postinjury. Patients were sorted into three treatment groups based on injury management: (1) Neither triage to trauma team activation (TTA) nor inpatient admission (Early Discharge), (2) Triage but no inpatient admission (Triage Only), and (3) Triage and In-patient. Outcomes included time from injury to first VOE, annual VOE counts requiring an emergency department (ED) visit, and ED length of stay (LOS) for the first VOE after injury. Results: Early Discharge individuals experienced a VOE event within 2.93 days of injury, significantly shorter time to event than Triage and In-patient individuals at 52.375 days and Triage Only individuals at 100.16 days (p=0.0058). No difference in annual VOE counts was noted postinjury across all groups. However, a significant increase in VOE LOS preinjury (16.1 hours) to postinjury (77.4 hours) was noted only for the Triage Only group (p=0.038). Cox regression model showed that shortened time to VOE events was marginally associated with TTA status (p=0.06). Conclusion: Despite minimal changes in long-term VOE outcomes after injury, traumatic injuries may accelerate the time-to-VOE among the Early Discharge group. Therefore, future research is warranted to analyze whether the absence of postinjury triage assessment and intervention may cause unforeseen physiologic stressors contributing to VOE outcomes. Level of evidence: Level IV: retrospective case-control study with three negative criteria.

Burnout in US hematologists and oncologists: impact of compensation models and advanced practice provider support.

Burnout is prevalent throughout medicine. Few large-scale studies have examined the impact of physician compensation or clinical support staff on burnout among hematologists and oncologists. In 2019, the American Society of Hematology conducted a practice survey of hematologists and oncologists in the AMA (American Medical Association) Masterfile; burnout was measured using a validated, single-item burnout instrument from the Physician Work-Life Study, while satisfaction was assessed in several domains using a 5-point Likert scale. The overall survey response rate was 25.2% (n = 631). Of 411 respondents with complete responses in the final analysis, 36.7% (n = 151) were from academic practices and 63.3% (n = 260) from community practices; 29.0% (n = 119) were female. Over one-third (36.5%; n = 150) reported burnout, while 12.0% (n = 50) had a high level of burnout. In weighted multivariate logistic regression models incorporating numerous variables, compensation plans based entirely on relative value unit (RVU) generation were significantly associated with high burnout among academic and community physicians, while the combination of RVU + salary compensation showed no significant association. Female gender was associated with high burnout among academic physicians. High advanced practice provider utilization was inversely associated with high burnout among community physicians. Distinct patterns of career dissatisfaction were observed between academic and community physicians. We propose that the implementation of compensation models not based entirely on clinical productivity increased support for women in academic medicine, and expansion of advanced practice provider support in community practices may address burnout among hematologists and oncologists.

Placenta growth factor in sickle cell disease: association with hemolysis and inflammation.

Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute chest syndrome. The observed correlation between PlGF and various measures of red cell destruction suggests that hemolysis, and the resultant erythropoietic response, results in the up-regulation of PlGF. Although relatively specific, PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular cell adhesion molecule, has low predictive accuracy for the presence of PHT. Prospective studies are required to conclusively define the contribution of PlGF to the pathogenesis of PHT and other hemolytic complications in SCD.