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Summary: Depressive symptoms are prevalent in individuals living with sickle cell disease (SCD) and may exacerbate pain. This study examines whether higher depressive symptoms are associated with pain outcomes, pain catastrophizing, interference and potential opioid misuse in a large cohort of adults with SCD. The study utilized baseline data from the 'CaRISMA' trial, which involved 357 SCD adults with chronic pain. Baseline assessments included pain intensity, daily mood, the Patient Health Questionnaire (PHQ), the Generalized Anxiety Disorders scale, PROMIS Pain Interference, Pain Catastrophizing Scale, the Adult Sickle Cell Quality of Life Measurement Information System and the Current Opioid Misuse Measure. Participants were categorized into 'high' or 'low' depression groups based on PHQ scores. Higher depressive symptoms were significantly associated with increased daily pain intensity, negative daily mood, higher pain interference and catastrophizing, poorer quality of life and a higher likelihood of opioid misuse (all p < 0.01). SCD patients with more severe depressive symptoms experienced poorer pain outcomes, lower quality of life and increased risk of opioid misuse. Longitudinal data from this trial will determine whether addressing depressive symptoms may potentially reduce pain frequency and severity in SCD. [ABSTRACT FROM AUTHOR]

Health‐related quality of life (HRQOL) is a patient‐reported outcome that assesses the impact of a disease or illness on different domains of a patient's life. Different general and disease‐specific measures can be used to evaluate HRQOL. This article aimed to summarize the evidence for HRQOL among patients with transfusion‐dependent (TDT) and non‐transfusion‐dependent thalassemia (NTDT). We included HRQOL data related to standard therapy with blood transfusions, iron chelation, and/or luspatercept in TDT and NTDT, as well as curative therapies for TDT, including hematopoietic stem cell transplant (HSCT) and gene therapy. Patients with thalassemia had worse HRQOL scores compared to the general population, and chronic pain was seen to increase in frequency and severity over time with age. NTDT patients reported worse physical health and functioning, mental health, general health, and vitality than TDT patients. However, TDT patients reported worse pain, change in health, and social support than NTDT. Most therapies improved overall HRQOL among thalassemia patients. Deferasirox, an oral iron chelator, was associated with more HRQOL benefits compared to deferoxamine, an intravenous iron chelator. Luspatercept showed clinically meaningful improvement in physical functioning among TDT and NTDT. Furthermore, HSCT and gene therapy were associated with better physical, emotional, and mental domains scores. [ABSTRACT FROM AUTHOR]

Summary: Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence‐based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow‐up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates. [ABSTRACT FROM AUTHOR]

Summary: It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post‐transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013–2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non‐relapse mortality (NRM). The analysis demonstrated a significant, non‐linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25–30 [hazard ratio (HR) 1.66–1.71, p < 0.05] and MUD transplants at a BMI of 25–45 (HR, 1.61–3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available. [ABSTRACT FROM AUTHOR]

Given that appropriate long-term iron chelation is essential in the treatment of transfusion-dependent anaemias,14,15 deferiprone b.i.d. has the potential to improve treatment adherence and health outcomes in patients with transfusional iron overload. Twenty-seven patients had a primary diagnosis of thalassaemia major, one patient had -thalassaemia/haemoglobin H disease and one patient had sickle -thalassaemia. Fourteen patients reported mild AEs, 13 patients reported moderate AEs and one patient reported a severe AE. Lifelong iron chelation therapy is critical for patients with transfusion-dependent anaemias, and full adherence to therapy is essential to optimise long-term patient outcomes.1,2 Deferiprone is an oral iron chelator with high efficiency in binding and removing excess intracellular and extracellular iron.3,4 Owing to its elimination half-life of approximately 2 h, deferiprone is administered three times daily (t.i.d.) to promote longer extent of exposure and better control of labile iron.5-7 Clinical trial data show adherence rates with deferiprone t.i.d. from 79% to 98%8,9; however, real-world adherence is generally lower than in clinical trials, as the t.i.d. regimen may be inconvenient and the midday dose may often be missed.10-12 The United States Food and Drug Administration recently approved a twice-a-day modified-release formulation of deferiprone (Ferriprox TAD 1000 mg tablet; manufactured by Apotex Inc., Toronto, Ontario, Canada) for the treatment of patients with transfusional iron overload due to thalassaemia syndromes, sickle cell disease or other anaemias.13 In single-dose and multiple-dose pharmacokinetic studies of deferiprone in healthy volunteers (Tables S1 and S2), we found that the twice-daily (b.i.d.) formulation had equivalent 24-h drug exposure to the original immediate-release tablet administered t.i.d. (Figure S1), and exposure was not affected by administration with food (Table S3). [Extracted from the article]

Control haemoglobinopathy blood safety project Keywords: sickle cell disease; thalassaemia; vaccines; iron overload; hepatitis EN sickle cell disease thalassaemia vaccines iron overload hepatitis e160 e164 5 11/30/21 20211201 NES 211201 Non-concordance with preventive recommendations is common among patients with chronic conditions, including sickle cell disease (SCD) and transfusion-dependent thalassaemia (TDT).1,2 Iron overload is common among chronically transfused patients with SCD and TDT leading to increased morbidity, mortality and cost of care, especially as they live longer.3-5 The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations support completion of hepatitis A (HepA) and hepatitis B (HepB) vaccinations, including SCD and TDT.6,7 Cardiac iron overload is the leading cause of mortality in TDT,8 while it is rare in SCD.9 Guidelines recommend liver iron overload assessment every 1-2 years for patients with SCD receiving chronic transfusions.10,11 The recommendation for TDT is annual assessment of liver and cardiac iron concentration.3,8 However, there are limited data on concordance with these recommendations. Child/adolescent patients with TDT who were concordant with HepA vaccination recommendations were concordant with the other two preventive service recommendations (Fig 1B). [Extracted from the article]

Background: The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes. Methods: This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014‐2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied. Results: The median age was 55 years (range, 18‐83 years). The median PCS was –0.21 (range, –1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was –0.13 (range, –1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00‐1.08; P =.0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00‐1.08; P =.0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02‐1.15; P =.0004). CCS was not significantly associated with survival, relapse, or NRM. Conclusions: Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes. A new community risk score for hematopoietic cell transplant recipients, derived from a large publicly available database (the County Health Rankings and Roadmaps), has been developed to describe the community health status of patients and transplant centers. A patient community risk score is associated with nonrelapse mortality and overall survival; however, a center community risk score is not associated with transplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression‐free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2. On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1‐1.7 [P =.06]), REL (HR, 1.03; 99% CI, 0.9‐1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1‐1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1‐1.4 [P =.02]) compared with the reference group (those aged 60‐69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2, including day 100 NRM (1% [95% CI, 1%‐2%] vs 0% [95% CI, 0%‐1%]; P =.003]), 2‐year PFS (64% [95% CI, 60%‐67%] vs 69% [95% CI, 66%‐73%]; P =.003), and 2‐year OS (85% [95% CI, 82%‐87%] vs 89% [95% CI, 86%‐91%]; P =.01]), likely representing frailty. Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups. Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy for the management of patients with multiple myeloma, which is a disease of older adults. The results of the current large database study confirm that AHCT remains an effective consolidation therapy in fit older adults aged ≥70 years. [ABSTRACT FROM AUTHOR]

We studied 2,528 patients with upfront autologous haematopoietic cell transplantation (AHCT) for multiple myeloma (MM) from 2008–2017 to develop a prognostic model to predict outcomes. High‐risk cytogenetics included t(4;14), t(14;16), t(14;20), del13q on karyotype, del17p, +1q or 1pdel. A Cox model identified factors prognostic of progression/relapse in a training subset (n = 1,246). A weighted score using these factors was assigned to a validation cohort (n = 774). Presence of high‐risk cytogenetics [hazard ratio, (HR) 1·68 (1·3–2·17)] and pre‐AHCT bone marrow plasma cells (BMPCs) ≥10% [1·68 (1·33–2·12)] were assigned 4 points each; albumin at diagnosis <3·5 g/dl [1·31 (1·07–1·61)] 2; standard risk cytogenetics 1, and no cytogenetics abnormality, BMPCs <10% at AHCT and albumin ≥3·5 g/dl at diagnosis 0 points each. A three‐category system with low risk (0–3), intermediate risk (4–8) and high risk (9–10) showed 3‐year progression‐free survival in the low vs. intermediate vs. high risk of 58% (95% CI: 52–63) vs. 49% (95% CI: 43–56) vs. 31% (95% CI: 12–51), P < 0.001 respectively, and 3‐year OS in low vs. intermediate vs. high risk of 88% (95% CI: 84–91) vs. 81% (95% CI: 76–86) vs. 64% (95% CI: 39–80); P < 0·001. Our prognostic scoring system can identify MM patients at risk for early relapse after AHCT. [ABSTRACT FROM AUTHOR]

Background: Although rituximab-based high-dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto-HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab-based conditioning on auto-HCT outcomes in patients who have DLBCL.Methods: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto-HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab-containing chemoimmunotherapy and had chemosensitive disease pre-HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS).Results: The study cohort was divided into 2 groups: BEAM (n = 667) and R-BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS (P = .83) or progression-free survival (PFS) (P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse (P = .15) or nonrelapse mortality (P = .12) was observed. Variables independently associated with lower OS included older age at auto-HCT (P < .001), absence of CR at auto-HCT (P < .001) and early chemoimmunotherapy failure (P < .001). Older age (P < .0002) and non-CR pre-HCT (P < .0001) were also associated with inferior PFS. There was no significant difference in early infectious complications between the 2 cohorts.Conclusion: In this large registry analysis of DLBCL patients undergoing auto-HCT, the addition of rituximab to the BEAM conditioning regimen had no impact on transplantation outcomes. Older age, absence of CR pre auto-HCT, and early chemoimmunotherapy failure were associated with inferior survival. [ABSTRACT FROM AUTHOR]

Objectives: The primary objectives were to (a) identify current published research in electronic health (eHealth) and mobile health (mHealth) interventions for youth undergoing cancer treatment and child, adolescent, and young adult survivors of childhood cancer and (b) critically appraise the current scientific evidence on their effectiveness and efficacy. As an exploratory aim, we identified pediatric cancer patients' and survivors' perceptions, attitudes, and concerns related to eHealth and mHealth interventions.Methods: A comprehensive search of the literature was performed to identify peer-reviewed journal articles that included the use of mHealth and eHealth interventions among youth receiving active cancer treatment and survivors of childhood cancer through the age range of childhood to young adulthood (mean age 21 years or younger at the time of diagnosis; mean age 39 years or younger at the time of intervention). The search was conducted via six electronic databases: PubMed, CINAHL, EMBASE, PsycINFO, IEEEXplore and the Cochrane Library.Results: Of the 1879 potential records examined, 21 met criteria for inclusion for a total of 1506 participants. Of the investigations included, 13 were randomized controlled trials, and eight were nonrandomized studies. Findings demonstrated feasibility as well as acceptability with these approaches. Evidence of efficacy for interventions targeting emotional distress, health behaviors, health outcomes, and neurocognitive functioning was mixed.Conclusions: Given the growing evidence of efficacy, coupled with increasing access to digital technologies, eHealth and mHealth may serve an important role in improving mental and physical health outcomes of youth undergoing cancer treatment and child, adolescent, and young adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To determine the factors associated with exercise capacity in adults with sickle cell disease (SCD) and its relationship to hospitalizations and mortality. Methods: A total of 223 participants in the Cooperative Study of Sickle Cell Disease (CSSCD) (64% female, 70% hemoglobin SS/Sβ0 thalassemia, mean age 43.3 ± 7.5 years) underwent maximal exercise testing using a treadmill protocol with a mean duration of 11.6 ± 5.2 minutes. Results: Female sex (β = −3.34, 95% CI [−1.80, −4.88], P < 0.001), older age (β = −0.14, 95% CI [−0.24, −0.04], P = 0.005), higher body mass index (β = −0.23, 95% CI [−0.37, −0.10]; P = 0.001), and lower hemoglobin (β = 0.56, 95% CI [0.08, 1.04], P = 0.02) were independently associated with lower fitness, while there was a trend with abnormal pulmonary function testing (β = −1.42, 95% CI [−2.92, 0.07]; P = 0.06). Lower percent‐predicted forced expiratory volume in 1 second (FEV1) was independently associated with lower fitness (β = 0.08, 95% CI [0.03, 0.13], P = 0.001). Genotype and hospitalization rates for pain and acute chest syndrome (ACS) prior to testing were not associated with exercise capacity. Baseline exercise capacity predicted neither future pain or ACS nor survival in our cohort. Adults with SCD tolerated maximal exercise testing. Conclusions: Prospective studies are needed to further evaluate the impact of regular exercise and improved fitness on clinical outcomes and mortality in SCD. [ABSTRACT FROM AUTHOR]

Objectives To identify barriers to hydroxyurea adherence (negative beliefs, access, and/or recall barriers), and their relationship to adherence rates and health-related quality of life ( HRQOL) among adolescents and young adults ( AYA) with sickle cell disease ( SCD). Methods A cross-sectional survey was administered to 34 AYAs (12-22 years old) in SCD clinics from January to December 2015. Study measures included Brief Medication Questionnaire, Modified Morisky Adherence Scale 8-items, visual analog scale, and Patient Reported Outcomes Measurement Information System. Results Participants (59% male; 91% Black) had a median age of 13.5 years ( IQR 12-18). Participants reported negative beliefs (32%), recall barriers (44%), and access barriers (32%). Participants with recall barriers reported worse pain ( P=.02), fatigue ( P=.05), and depression ( P=.05). The number of adherence barriers inversely correlated with adherence level using © MMAS-8 ( rs=−.38, P=.02) and VASdose ( rs=−.25, P=.14) as well as MCV ( rs=−.45, P=.01) and HbF% ( rs=−.36, P=.05), suggesting higher hydroxyurea adherence in patients with fewer barriers. Conclusions Patients with fewer barriers to hydroxyurea adherence were more likely to have higher adherence rates and better HRQOL scores. Routine assessment of hydroxyurea adherence and its related barriers could provide actionable information to improve adherence rates, HRQOL, and other clinical outcomes. [ABSTRACT FROM AUTHOR]

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease ( SCD) who receive chronic or episodic red blood cell transfusions. Iron-induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging ( MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long-term (over the 5 years prior to enrolment) mean serum ferritin ( MSF), spot-ferritin values and liver iron content ( LIC) measured using MRI and liver biopsy. Thirty-two SCD patients (median age 15 years) with transfusional iron overload were recruited from two U.S. institutions. Long-term MSF and spot-ferritin values significantly correlated with LIC by MRI-R2* ( r = 0·77, P < 0·001; r = 0·82, P < 0·001, respectively). LIC by MRI-R2* had strong positive correlation with LIC by liver biopsy ( r = 0·98, P < 0·001) but modest inverse correlation with cardiac MRI-T2* ( r = −0·41, P = 0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression. [ABSTRACT FROM AUTHOR]

The authors focus on the ineffectiveness of the medical flight kit (MFK) in treating children during in-flight medical emergencies (IME). Topics include the challenges of managing paediatric IME, the lack of medical equipment for infants in emergency situations in airlines under the U.S. Federal Aviation Administration (FAA) and European Aviation Safety Agency (EASA), and the need for paediatricians and commercial airlines to improve paediatric IME and ensure medical safety onboard.