Abstract

INTRODUCTION Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. METHODS This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. RESULTS Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence (n = 29) or "quantitatively" as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. CONCLUSIONS Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messagesPredictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort.Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes.Inadequate adherence to ICT is associated with increased lifetime health costs.There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.

Abstract

BACKGROUND AND OBJECTIVES Transfusion-dependent β-thalassaemia can lead to severe psychological issues in paediatric and adolescent patients. However, the psychological interventions for these patients are limited in clinical practice. We aimed to investigate the impact of a 3-month psychological intervention on the quality of life (QOL) of children with β-thalassaemia (12-18 years old) who relied on blood transfusion in this study. MATERIALS AND METHODS In the current randomized controlled trial, a total of 143 paediatric or adolescent patients (12-18 years old) with transfusion-dependent β-thalassaemia were recruited. They were randomized into the control group (n = 71) who received standard physiological treatment and the intervention group (n = 72) who received a 3-month intervention in addition to standard physiological treatment. The effects of the interventions on the QOL and psychological outcomes of these participants were analysed. RESULTS The 3-month intervention significantly improved the scores of PedsQoL 4.0 Generic Core Scales of paediatric patients with transfusion-dependent β-thalassaemia. It also significantly improved the psychological status and alleviated the depression among children and adolescent patients by alleviating anhedonia, negative mood and negative self-esteem among them. CONCLUSION Psychological intervention has positive effects on the treatment for children with transfusion-dependent β-thalassaemia.

Abstract

OBJECTIVE Preterm infants frequently receive red cell transfusions; however, the effect of transfusions on cognition is unclear. We evaluated the relationship between transfusions and cognitive outcomes in preterm infants enrolled in a randomized trial of erythropoiesis stimulating agents (ESAs). STUDY DESIGN Preterm infants were randomized to ESAs or placebo during initial hospitalization, and transfusions recorded. Children were evaluated using standard developmental tests of cognition at 18-22 months (56 ESA, 24 placebo) and 3.5-4 years (39 ESA, 14 placebo). RESULTS Cognitive scores at 18-22 months were inversely correlated with transfusion volume (p = 0.02). Among those receiving ≥1 transfusion, cognitive scores were significantly higher in the ESA-treated group (p = 0.003). At 3.5-4 years, transfusions were not correlated with cognitive scores. CONCLUSIONS In the placebo group, transfused children had lower cognitive scores than did non-transfused children at 18-22 months. In the ESA group, cognitive scores did not differ by transfusion status, suggesting ESAs might provide neuroprotection.

Abstract

BACKGROUND Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. PURPOSE To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. METHODS/SEARCH STRATEGY Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. FINDINGS Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. IMPLICATIONS FOR PRACTICE To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. IMPLICATIONS FOR RESEARCH It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.

Abstract

Background: Deferasirox is the first line of treatment in iron overload. In spite of the many studies concerning the efficacy of deferasirox, some patients remain unresponsive to deferasirox.Methods: One hundred and sixty patients were enrolled in stratified randomized controlled study. Patients were randomly divided into four regimens, group I (n=40) received 30 mg/kg deferasirox, group II (n=40) received 20 mg omeprazole and 30 mg/kg deferasirox, group III (n=40) received 400 mg vitamin E and 30 mg/kg deferasirox and group IV (n=40) received 420 mg silymarin and 30 mg/kg deferasirox. Blood specimens were collected from each patient for up to 24 h, and then plasma deferasirox concentrations were inspected.Results: Silymarin, Vitamin E and omeprazole significantly increased the peak plasma concentration of deferasirox (P<0.001) by 27.9, 14.9 and 2.4 fold respectively as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57 and 4.98-fold, respectively, following administration of omeprazole, vitamin E and silymarin compared to deferasirox alone.Conclusion: Silymarin, vitamin E and omeprazole represent promising adjuvant therapy to improve the chelation efficacy of deferasirox that might also be further applied to enhance the pharmacokinetics of deferasirox to overcome the lack of response.

Abstract

PURPOSE Red blood cell transfusion is a key element of treatment among patients with transfusion-dependent thalassemia (TDT). Volume overload and HCC syndrome (hypertension, convulsion, and intracranial hemorrhage) are fatal complications related to transfusion. Furosemide has been widely used to prevent hypertension secondary to volume overload with unclear supportive evidence. This study aimed to evaluate the efficacy of furosemide to prevent volume overload among children and young adults diagnosed with TDT. METHODS Patients diagnosed with TDT were enrolled and randomized to receive either furosemide pretransfusion or no furosemide pretransfusion. After 3 weeks to 4 months of wash-out periods, those patients underwent the alternate regimens as per crossover design of the study. Clinical and laboratory parameters including blood pressure and NT-proBNP levels were measured before and after each transfusion. The difference of those parameters between two randomized groups and their potential associated factors were analyzed. RESULTS In all, 30 patients undergoing 60 red blood cell transfusions were enrolled in the study. All were randomized and crossover was designed as receiving and not receiving furosemide pretransfusion. No transfusion reactions, symptoms of volume overload and HCC syndrome were observed. No statistically significant correlation was found between pretransfusion furosemide and the difference between pre- and posttransfusion systolic blood pressure (2 mmHg systolic blood pressure difference in pretransfusion furosemide and 1.5 mmHg in no pretransfusion furosemide; p-value = 0.721), as well as between pretransfusion furosemide and the difference between pre- and posttransfusion NT-proBNP levels (-3.8 pg/mL NT-proBNP level difference in pretransfusion furosemide and -2.4 pg/mL in no pretransfusion furosemide; p-value = 0.490). No significant correlation was also observed even in selected patients with high NT-proBNP levels (p-value = 0.262). Associated factors affecting the difference between pre- and posttransfusion NT-proBNP levels were analyzed, and none of those were affected concerning the difference in the levels. CONCLUSION Furosemide has been included in standard transfusion guidelines in many institutions. Our study provided important evidence of the unnecessary use of the drug in preventing volume overload particularly in pediatric and young adult patients with TDT. THAI CLINICAL TRIALS REGISTRY TCTR NUMBER TCTR20180209001. Registered 6 February 2018, https://www.clinicaltrials.in.th/.

Abstract

BACKGROUND β-Thalassemias are characterized by the presence of mutations in the globin gene that result in the absence or reduced synthesis of β-globin chains of the hemoglobin tetramer. Several studies have reported increased oxidative stress in β-thalassemia major (β-TM) patients. N-acetylcysteine (NAC), a derivative of L-cysteine amino acid, is commonly used as a mucolytic drug. Numerous studies have reported efficient antioxidant activity of NAC. PURPOSE To evaluate the effects of NAC on oxidative stress status and hemoglobin levels in children with β-TM. METHODS This study was conducted between June and December 2019. One hundred β-TM patients were divided into two groups: 50 received NAC 10 mg/kg orally for 3 months (treatment group), while the other 50 received no treatment (non-treatment group). Total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and hemoglobin (Hb) and ferritin levels were measured and compared between groups. RESULTS At the end of the study period, Hb and TAC levels were significantly higher in the treatment group than in the non-treatment group (P < .001 and .01, respectively). On the other hand, serum ferritin levels, TOS, and OSI were significantly lower (P = .004, .01, and .001, respectively) in the treatment group. CONCLUSION NAC can effectively reduce the oxidative status and increase the pre-transfusion Hb levels in children with β-TM. Furthermore, NAC could reduce iron overload in these patients.

Abstract

Transfusion-associated circulatory overload is the most frequent serious adverse transfusion reaction, with an incidence close to 1% of transfused patients in the general adult population. Patients in ICUs are probably more at risk of transfusion-associated circulatory overload as they are more frequently transfused and associated with more comorbidities. However, the epidemiology of transfusion-associated circulatory overload in ICU is not well characterized, leading to a risk of underdiagnosis. OBJECTIVES We conducted a scoping review to describe the incidence, risk factors, and outcomes of transfusion-associated circulatory overload in PICU and adult ICU. DATA SOURCES PubMed, Ovid Medline, Ovid All EBM Reviews, Ovid Embase, and EBSCO CINAHL COMPLETE. STUDY SELECTION Two reviewers independently screened each article for inclusion criteria. Studies were eligible if they reported data on incidence, risk factors, or outcomes of transfusion-associated circulatory overload in at least 10 ICU patients. DATA SYNTHESIS Among 5,926 studies identified, nine were included. Five studies were prospective, and four were retrospective. The definition of transfusion-associated circulatory overload varied among studies. The pooled incidence of transfusion-associated circulatory overload was of 5.5% (95% CI, 2.6-9.4%) in adult ICUs (four studies, 2,252 patients, high heterogeneity). In PICUs, two studies (345 patients) reported 0 cases, and a third study (136 patients) reported variable incidences between 1.5% and 76%, depending on diagnostic criteria. Risk factors for transfusion-associated circulatory overload included positive fluid balance, the number and type of products transfused, rate of transfusion, and cardiovascular and renal comorbidities. Transfusion-associated circulatory overload was associated with increased ICU and hospital lengths of stay, whereas the association with mortality was not consistent. CONCLUSIONS Transfusion-associated circulatory overload is frequent in ICU patients and is associated with adverse outcomes. The lack of a pediatric-adjusted definition of transfusion-associated circulatory overload may lead to a risk of underdiagnosis of this condition in PICUs. Further research is warranted to improve the knowledge of transfusion-associated circulatory overload and the safety of transfusion in ICU patients.

Abstract

Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N=64 their age ranged from10-18 (median 12) months, 54.7% males; receiving < or = 6 transfusions; serum ferittin (SF) >400-< 1000 ng/ml were randomized to "early start deferiprone" (.ES-DFP) at a low dose (50 mg/kg/day) or to "delay chelation" (DC), and remained in the study until their serum ferritin (SF) level reached ≥1000 mug/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months post-randomization, 100% of the subjects in DC group had achieved SF > 1000 microg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level >0.6 microM was observed in 97% vs. 40% of the DS and ES groups, respectively, (p<0.001). The time to reach SF>1000 microg/L was delayed by 6 months in the ES-DFP group (P<0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES-DFP group. This article is protected by copyright. All rights reserved.

Abstract

Limited evidence exists to support the withholding of feeds during packed red blood cell (PRBC) transfusion to reduce the incidence of transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants. The aim of the manuscript was to systematically review studies reporting the effect of implementing a policy of withholding feeds on the incidence of TANEC in preterm infants. The following databases were searched for relevant studies published between the databases' inception and December 2016: PubMed, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index of Nursing and Allied Health Literature, and Pediatric Academic Societies Abstract Archive. Other relevant sources were also searched. There were no restrictions on study design. Studies reporting on the incidence of TANEC (stage ≥2 necrotizing enterocolitis within 48-72 h) after implementation of a policy of withholding feeds in the peritransfusion period in preterm infants were included. This meta-analysis used a random-effects model with assessment of quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. There were no randomized controlled trials (RCTs). Pooled results from 7 non-RCTs (n = 7492) showed that withholding feeds during PRBC transfusion significantly reduced the incidence of TANEC (RR: 0.47; 95% CI: 0.28, 0.80; P = 0.005; I2 = 11%). The overall quality of evidence was moderate on GRADE analysis. These findings suggest that withholding feeds during the peritransfusion period may reduce the risk of TANEC in preterm infants. Adequately powered RCTs are needed to confirm these findings.