Hydroxyurea Adherence Strategies for Persons with Sickle Cell Disease: A Systematic Review
Journal of health care for the poor and underserved. 2021;32(1):99-118
INTRODUCTION Adherence to hydroxyurea is essential to modify the pathology of sickle cell disease. OBJECTIVE To identify best strategies to support adherence to hydroxyurea in persons with sickle cell disease. METHODS A systematic review was conducted. PubMed, Cumulative Index of Nursing and Allied Health Literature, PsycArticles, PsycInfo, Embase databases and Cochrane Library were searched for studies between 1998 to 2018. RESULTS Six studies met inclusion criteria: two randomized controlled trials, three prospective studies, and one retrospective chart review. DISCUSSION Few studies addressed strategies that tested adherence interventions primarily composed of behavioral change resulting in medication adherence. More studies on hydroxyurea adherence are needed.
Role of gene therapy in Fanconi anemia: A systematic and literature review with future directions
Hematology/oncology and stem cell therapy. 2021
Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ± 5.7 years. All patients had lentiviral-mediated GT. A 1-year follow-up showed stabilization in blood lineages, without any serious adverse effects from GT. A metaregression analysis could not be conducted, as very little long-term follow-up data of patients was observed, and the median survival rate could not be calculated. Thus, we can conclude that GT seems to be a safe procedure in FA; however, further research needs to be conducted on the longitudinal clinical effects of GT in FA, for a better insight into its potential to become a standard form of treatment.
Weekly epistaxis duration as an indicator of epistaxis severity in hereditary hemorrhagic telangiectasia-Preliminary results from a randomized controlled trial
Laryngoscope investigative otolaryngology. 2021;6(3):370-375
OBJECTIVES There is great interest in developing and studying novel therapies for epistaxis in hereditary hemorrhagic telangiectasia (HHT) given its associated morbidity and impact on patients' quality of life. Several recent randomized controlled trials (RCTs) have been negative, likely attributed to poorly characterized outcome measures. This study reported on and evaluated an epistaxis outcome measure, weekly epistaxis duration (WED) in an ongoing RCT, with the aim of better characterizing the measurement of epistaxis for clinical trials. MATERIALS AND METHODS Patients were recruited to an ongoing phase II, double-blind, cross-over RCTs of oral doxycycline for HHT-associated epistaxis. Patients were included for the epistaxis measures analysis if they had already completed the initial 3-month run-in period, and had received treatment of either study drug doxycycline or placebo for a minimum of 6 months. The primary measure of interest was patient-reported outcome (PRO)-WED, captured from prospective daily diaries. Epistaxis severity score (ESS) was collected as a secondary outcome. RESULTS Seven patients were included for analysis, with 98% completion of the daily diary. The average PRO-WED across all patients was 85.0 minutes, SD 93.2 at baseline, and 65.6 minutes, SD 59.5 during treatment/placebo. Coefficient of variance for PRO-WED at baseline and during treatment/placebo was 0.49, SD 0.1 and 0.58, SD 0.2, respectively. Statistically significant changes in the mean PRO-WED from baseline to treatment/placebo was noted in six patients (86%). Only two patients (29%) had a significant change in ESS, with both reporting decreased (improved) scores after treatment/placebo as compared to baseline. CONCLUSIONS PRO-WED was a feasible clinical trials measure, was reasonably stable during baseline measurement, and appeared to be variable with treatment state, suggesting it may provide a sensitive clinical trials PRO in HHT.
Transfusion management of severe anaemia in African children: a consensus algorithm
British journal of haematology. 2021
The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice.
Children presenting to hospital with both uncomplicated and complicated severe anaemia enrolled in the TRACT trial (n= 3,196).
Large volume of whole blood transfusion: 30 ml/kg, (n= 1,598).
Recommended blood volume transfusion by current WHO guidelines: 20 ml/kg (n= 1,598).
Transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia had strong but opposing effects on mortality, depending on fever status. There was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring.
Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis
Blood advances. 2021;5(8):2137-2141
The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (hazard ratio, 1.65; P < .001), a 72.6% reduction in the proportion of patients with the composite end point of TTP-related death, TTP exacerbation, or occurrence of at least 1 treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P < .001), and a 33.3% reduction in the median number of therapeutic plasma exchange days (5.0 vs 7.5 days) vs placebo. No new safety signals were identified; mild mucocutaneous bleeding was the main safety finding. This integrated analysis provided new evidence that caplacizumab prevents mortality and refractory disease in acquired TTP and strengthened individual trial findings, with a confirmed favorable safety and tolerability profile. These trials were registered at www.clinicaltrials.gov as #NCT01151423 and #NCT02553317.
A scoping review of transition interventions for young adults with sickle cell disease
Pediatric blood & cancer. 2021;:e29135
Standardized programming for individuals with sickle cell disease (SCD) transitioning from pediatric to adult-centered care does not currently exist, resulting in high rates of mortality and morbidity. This scoping review examines and evaluates the current literature on SCD transition programs and interventions. Eligible studies described an existing program for individuals with SCD aged 12-29 years preparing to transition. The Evidence Project risk-of-bias tool was used to assess article quality. We identified 30 eligible articles, of which, only two were randomized controlled trials. Many studies have incomplete reports of feasibility information, such as completion rates, patient characteristics, and attrition; all studies were limited to a single institution; and most studies were rated high for risk of bias. Progress has been made in designing and gathering initial evaluation data for SCD transition programs; however, there is a need for higher quality studies, consistent assessment, and better dissemination of programs.
Calcium Channel Blockers in Conjunction with Standard Iron-Chelating Agents for β-Thalassemia Major: Systematic Literature Search
Thalassemia is a genetic mutation of the α- or β-globin chains that lead to defective erythropoiesis. This study aimed to collect evidences from all published studies that investigated the clinical effectiveness of calcium channel blockers (CCBs) in conjunction with chelation therapy for reducing iron overload in patients with thalassemia. A systematic search was conducted in PubMed, Institute for Scientific Information (ISI) Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Virtual Health Library. Original studies reporting the use of CCBs in patients with thalassemia were included for meta-analysis. A total of five randomized studies including 210 patients were included with a follow-up period of 3-12 months. There was no significant difference between amlodipine and control groups in increasing the heart T2* magnetic resonance imaging (MRI) [mean difference (MD) 95% confidence interval (95% CI) = -1.9 (-4.4 to 0.5), p = 0.119] or reducing the liver iron concentration [MD 95% CI = -0.046 (-0.325 to 0.2), p = 0.746]. Although there were no serious adverse events reported in the included trials, further studies are recommended to strengthen our findings.
Psychological intervention in children with transfusion-dependent β-thalassaemia
Vox sanguinis. 2021
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.
Bleeding Assessment Tools in the Diagnosis of von Willebrand Disease: Systematic Review & Meta-Analysis of Test Accuracy
Blood advances. 2021
BACKGROUND Von Willebrand Disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. OBJECTIVE We systematically reviewed diagnostic test accuracy results of bleeding assessment tools (BATs) to screen patients for VWD. METHODS We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. RESULTS The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval [CI] 66%-83%) and 54% (29%-77%), respectively. Certainty of evidence varied from moderate to high. CONCLUSION This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates will influence patient management.
Coadministration of silymarin with iron chelators in transfusion-dependent β-thalassemia patients: a systematic review and meta-analysis for effect on iron overload
Expert review of clinical pharmacology. 2021;:1-9
Background and aim: We conducted a systematic review to apprise the efficacy of silymarin in conjunction with standard iron chelators on iron overload for transfusion-dependent β-thalassemia (TDT) patients.Methods: We searched PubMed, Web of Science, Scopus, Sciencedirect, the Cochrane Library (the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) to 1 May 2020. All randomized controlled trials (RCTs) studies comparing the effect of iron chelators alone versus silymarin plus standard routine treatment on iron burden amid TDT were included in this review. Primary outcomes comprised serum ferritin level (ng/mL), liver iron concentration (LIC Fe/kg dry weight), and total iron binding capacity (TIBC mcg/dL)Results: Combination therapy of silymarin and iron chelators showed a significant improvement in serum ferritin level in TDT patients, compared to nonsilymarin users [eight studies, n = 477]; weighted mean difference (WMD) -1.79, 95% confidence interval [CI] -2.86 to -0.72, I(2) 96.1%; P = 0.001. Concurrent treatment with silymarin failed to significantly decrease LIC in TDT patients [two studies, n = 106]; WMD 0.74, 95% CI -1.62 to 3.10, I(2) 96.6%; P = 0.54.Conclusion: There is no evidence of the effectiveness of adding silymarin to standard iron chelators to reduce iron load in TDT.