Attitudes, Beliefs, and Intention to Receive a COVID-19 Vaccine for Pediatric Patients With Sickle Cell Disease.

Sickle cell disease (SCD), which occurs primarily in individuals of African descent, has been identified as a preexisting health condition for COVID-19 with higher rates of hospitalization, intensive care unit admissions, and death. National data indicate Black individuals have higher rates of vaccine hesitancy and lower COVID-19 vaccination rates. Understanding the key predictors of intention to receive a COVID-19 vaccine is essential as intention is strongly associated with vaccination behavior. This multisite study examined attitudes, beliefs, intentions to receive COVID-19 vaccines, and educational preferences among adolescents, young adults, and caregivers of children living with SCD. Participants completed an online survey between July 2021 and March 2022. Multivariate logistic regression was used to examine the association between participant age and COVID-19 vaccine attitudes, beliefs, and vaccine intentions. Of the 200 participants, 65.1% of adolescents, 62.5% of young adults, and 48.4% of caregivers intended to receive a COVID-19 vaccine for themselves or their child. Perception that the vaccine was safe was statistically significant and associated with patient and caregiver intention to receive the COVID-19 vaccine for themselves or their child. Participant age was also statistically significant and associated with the intent to get a booster for patients. Study findings highlight key concerns and influencers identified by patients with SCD and their caregivers that are essential for framing COVID-19 vaccine education during clinical encounters. Study results can also inform the design of messaging campaigns for the broader pediatric SCD population and targeted interventions for SCD subpopulations (eg, adolescents, caregivers).

Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024.

We report highly pathogenic avian influenza A(H5N1) virus in dairy cattle and cats in Kansas and Texas, United States, which reflects the continued spread of clade 2.3.4.4b viruses that entered the country in late 2021. Infected cattle experienced nonspecific illness, reduced feed intake and rumination, and an abrupt drop in milk production, but fatal systemic influenza infection developed in domestic cats fed raw (unpasteurized) colostrum and milk from affected cows. Cow-to-cow transmission appears to have occurred because infections were observed in cattle on Michigan, Idaho, and Ohio farms where avian influenza virus-infected cows were transported. Although the US Food and Drug Administration has indicated the commercial milk supply remains safe, the detection of influenza virus in unpasteurized bovine milk is a concern because of potential cross-species transmission. Continued surveillance of highly pathogenic avian influenza viruses in domestic production animals is needed to prevent cross-species and mammal-to-mammal transmission.

Real-world evidence: Long-term safety of deferiprone in a large cohort of patients with sickle cell disease enrolled in a registry for up to 10 years.

Patients with sickle cell disease (SCD) and other anemias who receive blood transfusions are at risk of organ damage due to transfusional iron overload. Deferiprone is an iron chelator with a well-established safety and efficacy profile that is indicated for the treatment of transfusional iron overload. Here, we report safety data from the large-scale, retrospective Ferriprox® Total Care Registry, which involved all patients with SCD taking deferiprone following the 2011 approval of deferiprone in the United States through August 2020. A total of 634 patients who had initiated deferiprone treatment were included. The mean (SD) duration of deferiprone exposure in the registry was 1.6 (1.6) years (range 0 to 9.7 years). In the overall patient population (N = 634), 64.7% (n = 410) of patients reported a total of 1885 adverse events (AEs). In subgroup analyses, 54.6% (n = 71) of pediatric patients and 67.3% (n = 339) of adult patients reported AEs. The most common AEs reported in patients receiving deferiprone were sickle cell crisis (22.7%), nausea (12.1%), vomiting (8.7%), abdominal discomfort (5.4%), and fatigue (5.4%). Neutropenia was reported in four (0.6%) patients and severe neutropenia/agranulocytosis (defined as absolute neutrophil count <0.5 × 109/L) was reported in two (0.3%) patients. Of patients with evaluable data, all cases of neutropenia and severe neutropenia/agranulocytosis resolved with deferiprone discontinuation. Results from the nearly 10 years of real-world data collected in the Ferriprox® Total Care Registry demonstrate that deferiprone is safe and well tolerated in patients with SCD or other anemias who have transfusional iron overload.

Burden of employment loss and absenteeism in adults and caregivers of children with sickle cell disease.

ABSTRACT: Sickle cell disease (SCD) is a genetic disorder affecting 100 000 people with an estimated annual medical cost of $3 billion in the United States; however, the economic impact on patients is not well described. We aimed to examine the indirect economic burden and test the hypothesis that socioeconomic status and greater social vulnerability risks are associated with increased absenteeism and employment loss. We surveyed adults and caregivers of children with SCD at 5 US centers from 2014 to 2021. Logistic regression models were used to examine the associations of employment loss and missed days of work with demographics and social determinants. Indirect costs were estimated by multiplying the self-reported missed days of work and job loss by 2022 average wages by the state of the participating institution. Of the 244 participants, 10.3% reported employment loss in the last 5 years, and 17.5% reported missing 10 or more days of work. Adults had 3 times more employment loss compared with caregivers of children with SCD (OR, 3.18; 95% CI, 1.12-9.01) but fewer missed days of work (OR, 0.24; 95% CI, 0.11-0.0.51). Participants who did not live with a partner reported increased employment loss (OR, 4.70; 95% CI, 1.04-21.17) and more missed days of work (OR, 4.58; 95% CI, 1.04-20.15). The estimated annual indirect economic burden was $2 266 873 ($9290 per participant). Adults with SCD and caregivers of children with SCD commonly report employment loss and missed days of work as important risk factors. The high indirect economic burden suggests that future economic evaluations of SCD should include SCD-related indirect economic burden.

Safety of Ultrasound Contrast Agents in Pediatric Patients With Sickle Cell Disease and Trait.

Ultrasound contrast agent (UCA) use is increasing. Recent isolated reports observed a rise in pain-related adverse events with the intravenous administration of the UCA Definity in adults with sickle cell disease. To date, no studies have investigated the incidence of similar adverse events with UCA Lumason or Optison. We describe our experience regarding the safety of Lumason and Optison in children with sickle cell disease and trait who underwent contrast-enhanced ultrasound exams in our department with intravenous, intravesical, and other intracavitary routes. No pain-related or other adverse events were observed in this pediatric population with any route of UCA administration.

Estimating IgG concentration directly by radial immunodiffusion or indirectly by refractometry measure of serum total protein lack precision.

OBJECTIVE: To establish and compare the precision of serum total protein (STP) measured by an optical refractometer to the precision of IgG concentrations measured using radial immunodiffusion (RID), the reference test for quantifying IgG in neonatal calves. SAMPLE: 6 sera with previously measured IgG concentration using RID from neonatal beef calves were selected from 3 stratum: low-serum IgG stratum between >5.0 and <15.0g/L(n = 4); moderate-serum IgG stratum between 35.0-45.0g/L(n = 1); high-serum IgG stratum between 60.0-70.0g/L(n = 1). METHODS: STP was measured 13 times with an optical refractometer. IgG concentrations were measured 28 times with a commercial bovine IgG RID for each sera. The homogeneity of variance within the tests was evaluated with the Levene test (α = 0.10). Unrestricted random sampling bootstrapping (5,000 repetitions) was used to calculate the coefficient of variation (CV) for each serum and test. The homogeneity of variance between simulated test CVs by serum was evaluated (α = 0.10). Differences between simulated test CV by serum were assessed with the Kruskal-Wallis test (α = 0.05). RESULTS: No difference was observed in the variance for STP between sera (P = .39). The average CV for STP was 4.2%, 10.1% for the low IgG stratum, and 15.5% for the moderate/high IgG stratum. Variance differed in serum IgG concentration (P < .0001). Serum with higher IgG concentrations had more variance. Simulated CV for STP and IgG had homogeneity of variance for only 1 sera (P = .31). STP had a smaller CV compared to IgG for every serum (P < .0001). CLINICAL RELEVANCE: Estimating IgG concentration directly by RID or indirectly by STP lacks the precision that might affect diagnostic interpretation regarding a calf's absorption of maternal antibodies.

Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial.

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults. METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant's randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE. DISCUSSION: Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children. TRIAL REGISTRATION: The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354).

Immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients with severe hemophilia A: interim results from a phase 3, prospective, multicenter, open-label study.

AIM: To determine the immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients (PUPs) with severe hemophilia A (HA). METHODS: This prospective, phase 3 study (NCT02615691) was conducted in PUPs, or patients with ≤2 exposure days (EDs) prior to screening, aged <6 years with severe HA. The primary endpoint was incidence of factor VIII (FVIII) inhibitor development. This protocol-specified interim analysis was conducted after 50 patients had completed ≥50 EDs without developing FVIII inhibitors or had developed a confirmed inhibitor at any time. RESULTS: Of the enrolled patients, 59/80 (73.8%) received ≥1 dose of rurioctocog alfa pegol; 54 received prophylaxis, and 35 on-demand treatment. Incidence of inhibitor development was 0.19 (10/52). Total annualized bleeding rate (95% CIs) was 3.2 (2.0-5.0) for patients receiving prophylaxis and 3.2 (1.6-6.3) for on-demand treatment. Hemostatic efficacy of most bleedings was rated as 'excellent' or 'good' after 24 hours (122/131 [93.1%]) and at resolution (161/170 [94.7%]). Five patients received ≥1 dose of rurioctocog alfa pegol for immune tolerance induction (ITI) and 1 patient was defined as having ITI success. Thirteen patients experienced 14 treatment-related adverse events, including 10 cases of FVIII inhibitor development. CONCLUSION: This is the first prospective study of rurioctocog alfa pegol for the treatment of PUPs with severe HA. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02615691).

Return visit rates after an emergency department discharge for children with sickle cell pain episodes.

BACKGROUND: High return visit rates after hospitalization for people with sickle cell disease (SCD) have been previously established. Due to a lack of multicenter emergency department (ED) return visit rate data, the return visit rate following ED discharge for pediatric SCD pain treatment is currently unknown. PROCEDURE: A seven-site retrospective cohort study of discharged ED visits for pain by children with SCD was conducted using the Pediatric Emergency Care Applied Research Network Registry. Visits between January 2017 and November 2021 were identified using previously validated criteria. The primary outcome was the 14-day return visit rate, with 3- and 7-day rates also calculated. Modified Poisson regression was used to analyze associations for age, sex, initial hospitalization rate, and a visit during the COVID-19 pandemic with return visit rates. RESULTS: Of 2548 eligible ED visits, approximately 52% were patients less than 12 years old, 50% were female, and over 95% were non-Hispanic Black. The overall 14-day return visit rate was 29.1% (95% confidence interval [CI]: 27.4%-30.9%; site range 22.7%-31.7%); the 7- and 3-day return visit rates were 23.0% (95% CI: 21.3%-24.6%) and 16.7% (95% CI: 15.3%-18.2%), respectively. Younger children had slightly lower 14-day return visit rates (27.3% vs. 31.1%); there were no associations for site hospitalization rate, sex, and a visit occurring during the pandemic with 14-day returns. CONCLUSION: Nearly 30% of ED discharged visits after SCD pain treatment had a return visit within 14 days. Increased efforts are needed to identify causes for high ED return visit rates and ensure optimal ED and post-ED care.

Assessment of accredited veterinary diagnostic laboratory use of breakpoints for canine and feline Escherichia coli infections in the United States and Canada.

The objective of this study was to assess the use of breakpoints in antibiotic susceptibility testing among veterinary diagnostic laboratories in the United States and Canada. An eight-question survey was conducted via phone and email to determine how often laboratories use breakpoints consistent with published guidelines in wounds, lower urinary tract infections and upper urinary tract infections (pyelonephritis) involving Escherichia coli, both in dogs and cats, for a total of 6 different hypothetical clinical scenarios. Nineteen veterinary diagnostic laboratories that perform antibiotic susceptibility testing on samples from dogs and cats in the United States or Canada and were accredited by the American Association of Veterinary Laboratory Diagnosticians (AAVLD) responded to the survey between January 15th and September 15th, 2022. The overall response rate of laboratories that were not excluded for known lack of dog and cat antibiotic susceptibility testing was 19 of 44 laboratories. Of the 17 respondent laboratories that reported using minimal inhibitory concentration breakpoints, only four laboratories used breakpoints consistent with published guidelines in all six clinical scenarios included in the survey. Our results suggest that there is clinically important variation in what breakpoints laboratories use to determine antibiotic susceptibility, which is of antibiotic stewardship and clinical relevance. Using breakpoints that are too high, too low, or inappropriately reporting "not interpreted" as the interpretive category may result in inappropriate use of antibiotics.

Psychologists as leaders in equitable science: Applications of antiracism and community participatory strategies in a pediatric behavioral medicine clinical trial.

Psychologists have an ethical responsibility to advance health equity and can play a significant role in improving health care experiences for families racialized as Black, including those with sickle cell disease (SCD), a group of genetic blood disorders primarily affecting communities of color. Parents of children with SCD report experiences of stigma and discrimination due to racism in the health care system. The current commentary describes the application of antiracism and participatory strategies to the research design, implementation, and dissemination of a behavioral medicine clinical trial (Engage-HU; NCT03442114) of shared decision-making (SDM) for pediatric patients with SCD, including (a) the development of a research question to promote justice for racialized groups; (b) a focus on "redressing imbalances" through SDM and a multidisciplinary, inclusive research team led by a Black psychologist; (c) community participatory approaches through the integration of stakeholder feedback across the study; and (d) centering context by attending to structural realities in response to the COVID-19 and racism pandemics. With attention to the fact that most primary caregivers of children with SCD are Black women, an intersectionality lens was applied. Implications and considerations for psychologists working to advance health equity in medical settings are also discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Health-related quality of life in patients with ß-thalassemia: Data from the phase 3 BELIEVE trial of luspatercept.

BACKGROUND: Patients with transfusion-dependent (TD) ß-thalassemia require long-term red blood cell transfusions (RBCTs) that lead to iron overload, impacting health-related quality of life (HRQoL). METHODS: The impact of luspatercept, a first-in-class erythroid maturation agent, versus placebo on HRQoL of patients with TD ß-thalassemia was evaluated in the phase 3 BELIEVE trial. HRQoL was assessed at baseline and every 12 weeks using the 36-item Short Form Health Survey (SF-36) and Transfusion-dependent Quality of Life questionnaire (TranQol). Mean change in HRQoL was evaluated from baseline to week 48 for patients receiving luspatercept + best supportive care (BSC) and placebo + BSC and between luspatercept responders and non-responders. RESULTS: Through week 48, for both groups, mean scores on SF-36 and TranQol domains were stable over time and did not have a clinically meaningful change. At week 48, more patients who achieved clinical response (≥50% reduction in RBCT burden over 24 weeks) in the luspatercept + BSC group had improvement in SF-36 Physical Function compared with placebo + BSC (27.1% vs. 11.5%; p = .019). CONCLUSIONS: Luspatercept + BSC reduced transfusion burden while maintaining patients' HRQoL. HRQoL domain improvements from baseline through 48 weeks were also enhanced for luspatercept responders.

The effect of an aiming device on the accuracy of humeral transcondylar screw placement.

OBJECTIVES: (1) To evaluate the accuracy of an aiming device on placement of humeral transcondylar screws compared to fluoroscopic methods. (2) To compare experience level on outcome. STUDY DESIGN: Randomized, match pair, prospective ex-vivo study. SAMPLE POPULATION: A total of 68 dogs. METHODS: Canine cadaveric forelimbs were randomly assigned to either aiming device or fluoroscopic-guided groups, and to diplomate or resident. Digital radiography was used to evaluate screw trajectory deviation and eccentricity on the humeral condyle. Procedure time, outcome based on experience, and complications were recorded. RESULTS: The aiming device screw trajectory angle was decreased in the right limb (1.9 ± 1.1°) compared with the left (3.6 ± 1.1°, p = .0178), and compared to fluoroscopy (3.4 ± 1.1° p = .0128). There was no difference between leg laterality with fluoroscopy (p = .9979). Trajectory angle was increased with resident versus diplomate (3.4 ± 1.1° and 2.5 ± 1.1° respectively, p = .0366). Eccentricity deviation was decreased using fluoroscopy versus aiming device (3.1 ± 0.36 mm, 4.2 ± 0.36 mm, respectively, p = .0017). The risk of joint involvement was 8 times greater in aiming device groups, though not significant (p = .0575). Significant complications included increased drill attempts in fluoroscopic groups (p = .0237). CONCLUSION: The aiming device provided accurate placement of transcondylar screws, in terms of both position on the condyle and trajectory angle. Results were similar to fluoroscopic-guided method. CLINICAL SIGNIFICANCE: An aiming device is an acceptable means of placing humeral transcondylar screws. The use of the aiming device had an eight times increased risk of joint involvement compared to fluoroscopy.

Cardiac Magnetic Resonance Strain in Beta Thalassemia Major Correlates with Cardiac Iron Overload.

BACKGROUND: Beta thalassemia major (Beta-TM) is an inherited condition which presents at around two years of life. Patients with Beta-;TM may develop cardiac iron toxicity secondary to transfusion dependence. Cardiovascular magnetic resonance (CMR) T2*, a technique designed to quantify myocardial iron deposition, is a driving component of disease management. A decreased T2* value represents increasing cardiac iron overload. The clinical manifestation is a decline in ejection fraction (EF). However, there may be early subclinical changes in cardiac function that are not detected by changes in EF. CMR-derived strain assesses myocardial dysfunction prior to decline in EF. Our primary aim was to assess the correlation between CMR strain and T2* in the Beta-TM population. METHODS: Circumferential and longitudinal strain was analyzed. Pearson's correlation was calculated for T2* values and strain in the Beta-TM population. RESULTS: We identified 49 patients and 18 controls. Patients with severe disease (low T2*) were found to have decreased global circumferential strain (GCS) in comparison to other T2* groups. A correlation was identified between GCS and T2* (r = 0.5; p < 0.01). CONCLUSION: CMR-derived strain can be a clinically useful tool to predict early myocardial dysfunction in Beta-TM.

Secondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease.

PURPOSE: To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease. METHODS: Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemia/myelodysplastic syndrome (MDS; n = 15) and solid tumor (n = 7). Fine-Gray regression models examined for risk factors for leukemia/MDS and any secondary neoplasm. RESULTS: The 10-year incidence of leukemia/MDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemia/MDS (hazard ratio, 22.69; 95% CI, 4.34 to 118.66; P = .0002) or any secondary neoplasm (hazard ratio, 7.78; 95% CI, 2.20 to 27.53; P = .0015) were higher with low-intensity (nonmyeloablative) regimens compared with more intense regimens. All low-intensity regimens included total-body irradiation (TBI 300 or 400 cGy with alemtuzumab, TBI 300 or 400 cGy with cyclophosphamide, TBI 200, 300, or 400 cGy with cyclophosphamide and fludarabine, or TBI 200 cGy with fludarabine). None of the patients receiving myeloablative and only 23% of those receiving reduced-intensity regimens received TBI. CONCLUSION: Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemia/MDS.

Placentophagia and the Tao of POEF.

Placentophagia, ingestion of placenta and amniotic fluid, usually during parturition, is a behavioral feature of nearly all nonaquatic, placental mammals, and is a nexus for several interlocking behavioral phenomena. Placentophagia has not been typical of human cultures, but in recent years, some women in affluent societies have engaged in it, thereby bringing publicity to the behavior. First, we summarized benefits of placentophagia for nonhuman mammals, which include increased attractiveness of neonates, enhanced onset of maternal behavior, suppression of pseudopregnancy, and enhancement of opioid hypoalgesia by Placental Opioid-Enhancing Factor (POEF), a benefit that may extend well outside the context of parturition. The research on POEF in animals was discussed in detail. Then we discussed placentophagia (placentophagy) in humans, and whether there is validity to the claims of various benefits reported primarily in the pro-placentophagy literature, and, although human afterbirth shows POEF activity, the POEF effect has not yet been tested in humans. Finally, we discussed the general possible implications, for the management of pain and addiction, of isolating and characterizing POEF.

Sources of variance in the results of a commercial bovine immunoglobulin G radial immunodiffusion assay.

Radial immunodiffusion (RID) is used to quantify IgG concentration in neonatal beef or dairy calf serum; variability has been noted that may affect the precision and accuracy of assay results. We determined the source, range, and homogeneity of variance in the results of a commercial bovine IgG RID assay (Triple J Farm). To estimate the variance in the precipitin ring diameter, we used 6 sera, measured 28 times across 8 plates and 4 lots, and 3 standards with known IgG concentrations, measured 75 times across 69 plates and 5 lots. The source of diameter variance was determined using variance partition coefficients for lot, plate, and repetition. We used 11 different methods to generate standard curves to convert RID precipitin ring diameters to IgG concentrations. The Levene test of homogeneity of variance (α = 0.1) was used to evaluate the equality of variance between the standards or serum precipitin ring diameters and calculated IgG concentrations. Lot and plate contributed minimally to the diameter variance. Precipitin ring diameters had equal variance. Calculated IgG concentrations for serum not requiring dilution had equal variance. A linear equation from aggregated standards, performed within the same day, had greater accuracy for the calculated IgG concentrations of the standards compared to other equation methods. Regardless of standard curve methodology or IgG concentration, variability inherent to the assay limits its clinical usefulness.