The role of hydroxyurea to prevent silent stroke in sickle cell disease: Systematic review and meta-analysis
Hasson C, Veling L, Rico J, Mhaskar R
BACKGROUND Chronic blood transfusions are standard of care for stroke prevention in sickle cell disease but is not cost effective and not without risks. Hydroxyurea has emerged as an option in the prevention of silent stroke in sickle cell disease. OBJECTIVE To evaluate the role of hydroxyurea in preventing silent strokes in a systematic review by adhering to the Cochrane guidelines. METHODS PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials were searched for the related articles. Eligibility criteria included randomized controlled trials (RCTs) comparing the use of hydroxyurea vs blood transfusions and observational studies evaluating the role of hydroxyurea to prevent stroke and silent stroke in patients with sickle cell anemia or sickle cell beta thalassemia. The meta-analysis was conducted using STATA software version 13. RESULTS We included 10 single arm observational studies with 361 participants, and one RCT study with 60 participants receiving hydroxyurea, respectively. There were no deaths attributed to hydroxyurea. The results revealed that 1% (95% CIs 0.0 to 0.05) of patients receiving hydroxyurea had stroke. 18% (95% CIs 0.03 to 0.4) of the hydroxyurea patients had silent stroke. 24% (95% CIs 0.02 to 0.57) of the hydroxyurea patients had adverse events attributed to hydroxyurea. CONCLUSION Our findings suggest that hydroxyurea is safe and may prevent silent stroke and stroke in sickle cell disease. More high-quality studies including RCTs are needed.
The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents
Mhaskar R, Wao H, Miladinovic B, Kumar A, Djulbegovic B
The Cochrane Database of Systematic Reviews. 2016;((2)):CD009624.
BACKGROUND Erythropoiesis-stimulating agents (ESAs) are commonly used to treat chemotherapy-induced anemia (CIA). However, about half of patients do not benefit. OBJECTIVES To evaluate the benefits and harms related to the use of iron as a supplement to ESA and iron alone compared with ESA alone in the management of CIA. SEARCH METHODS We searched for relevant trials from the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1 January 2016), MEDLINE (1950 to February 2016), and www.clinicaltrials.gov without using any language limits. SELECTION CRITERIA All randomized controlled trials (RCTs) comparing 'iron plus ESA' or 'iron alone' versus 'ESA alone' in people with CIA were eligible for inclusion. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included eight RCTs (12 comparisons) comparing ESA plus iron versus ESA alone enrolling 2087 participants. We did not find any trial comparing iron alone versus ESAs alone in people with CIA. None of the included RCTs reported overall survival. There was a beneficial effect of iron supplementation to ESAs compared with ESAs alone on hematopoietic response (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.09 to 1.26; P < 0.0001; 1712 participants; 11 comparisons; high-quality evidence). Assuming a baseline risk of 35% to 80% for hematopoietic response without iron supplementation, between seven and 16 patients should be treated to achieve hematopoietic response in one patient. In subgroup analyses, RCTs that used intravenous (IV) iron favored ESAs and iron (RR 1.20 (95% CI 1.10 to 1.31); P < 0.00001; 1321 participants; eight comparisons), whereas we found no evidence for a difference in hematopoietic response in RCTs using oral iron (RR 1.04 (95% CI 0.87 to 1.24); P = 0.68; 391 participants; three comparisons). There was no evidence for a difference between the subgroups of IV and oral iron (P = 0.16). There was no evidence for a difference between the subgroups of types of iron (P = 0.31) and types of ESAs (P = 0.16) for hematopoietic response.The iron supplementation to ESAs might be beneficial as fewer participants treated with iron supplementation required red blood cell (RBC) transfusions compared to the number of participants treated with ESAs alone (RR 0.74 (95% CI 0.60 to 0.92); P = 0.007; 1719 participants; 11 comparisons; moderate-quality evidence). Assuming a baseline risk of 7% to 40% for RBC transfusion without iron supplementation, between 10 and 57 patients should be treated to avoid RBC transfusion in one patient.We found no evidence for a difference in the median time to hematopoietic response with addition of iron to ESAs (hazard ratio (HR) 0.93 (95% CI 0.67 to 1.28); P = 0.65; 1042 participants; seven comparisons; low-quality evidence). In subgroup analyses, RCTs in which dextran (HR 0.95 (95% CI 0.36 to 2.52); P = 0.92; 340 participants; three comparisons), sucrose iron (HR 1.15 (95% CI 0.60 to 2.21); P = 0.67; 102 participants; one comparison) and sulfate iron (HR 1.24 (95% CI 0.99 to 1.56); P = 0.06; 55 participants; one comparison) were used showed no evidence for difference between iron supplementation versus ESAs alone compared with RCTs in which gluconate (HR 0.78 (95% CI 0.65 to 0.94); P = 0.01; 464 participants; two comparisons) was used for median time to hematopoietic response (P = 0.02). There was no evidence for a difference between the subgroups of route of iron administration (P = 0.13) and types of ESAs (P = 0.46) for median time to hematopoietic response.Our results indicated that there could be improvement in the hemoglobin (Hb) levels with addition of iron to ESAs (mean difference (MD) 0.48 (95% CI 0.10 to 0.86); P = 0.01; 827 participants; seven comparisons; low-quality evidence). In RCTs in which IV iron was used there was evidence for a difference (MD 0.84 (95% CI 0.21 to 1.46); P = 0.009; 436 participants; four comparisons) compared with oral iron (MD 0.07 (95% CI -0.19 to 0.34); P = 0.59; 391 participants; three comparisons) for mean change i
Platelet transfusion: a systematic review of the clinical evidence
Kumar A, Mhaskar R, Grossman BJ, Kaufman RM, Tobian AA, Kleinman S, Gernsheimer T, Tinmouth AT, Djulbegovic B, AABB Platelet Transfusion Guidelines Panel
BACKGROUND Platelet (PLT) transfusion is indicated either prophylactically or therapeutically to reduce the risk of bleeding or to control active bleeding. Significant uncertainty exists regarding the appropriate use of PLT transfusion and the optimal threshold for transfusion in various settings. We formulated 12 key questions to assess the role of PLT transfusion. STUDY DESIGN AND METHODS We performed a systematic review (SR) of randomized controlled trials (RCTs) and observational studies. A comprehensive search of PubMed, Web of Science, and Cochrane registry of controlled trials was performed. Methodologic quality of included studies was assessed and a meta-analysis was performed if more than two studies with similar designs were identified for a specific question. RESULTS Seventeen RCTs and 55 observational studies were included in the final SR. Results from RCTs showed a beneficial effect of prophylactic compared with therapeutic transfusion for the prevention of significant bleeding in patients with hematologic disorders undergoing chemotherapy or stem cell transplantation. We found no difference in significant bleeding events related to the PLT count threshold for transfusion or the dose of PLTs transfused. Overall methodologic quality of RCTs was moderate. Results from observational studies showed no evidence that PLT transfusion prevented significant bleeding in patients undergoing central venous catheter insertions, lumbar puncture, or other surgical procedures. The methodologic quality of observational studies was very low. CONCLUSION We provide a comprehensive assessment of evidence on the use of PLT transfusions in a variety of clinical settings. Our report summarizes current knowledge and identifies gaps to be addressed in future research.Copyright © 2014 AABB.