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Hydroxyurea for secondary stroke prevention in children with sickle cell anaemia: a systematic review of clinical evidence and outcomes
Aderinto, N., Olatunji, G., Kokori, E., Abdulbasit, M.
Annals of medicine and surgery (2012). 2024;86(2):1042-1047
Abstract
BACKGROUND Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea's effectiveness and safety in preventing secondary strokes in paediatric SCA patients. METHODS This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention. RESULTS A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels. CONCLUSION Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.
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Efficacy and safety of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis
Wang, L., He, M., Wang, W., Li, S., Zhao, G.
European journal of pediatrics. 2024
Abstract
Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However, the efficacy of infliximab in primary treatment of Kawasaki disease (KD) or retreatment of intravenous immunoglobulin (IVIG)-resistant KD in children is controversial. Therefore, we conducted a meta-analysis to compare the efficacy of infliximab alone or in combination with IVIG to IVIG. Eligible randomized and non-randomized trials were retrieved by searching literature databases prior to May 31, 2023. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous variables, and mean difference (MD) with 95% CI was estimated for continuous variables. A total of 14 eligible studies comprising 1257 participants were included. In refractory KD, infliximab alone was associated with a higher effectiveness rate (OR = 4.48, 95% CI 2.67-7.52) and defervescence rate (OR = 5.01, 95% CI 2.99-8.37) and resulted in a 1.08-day-shorter duration of fever (95% CI 0.61-1.55, P < 0.001) and 1.36-day-shorter length of hospital stay (95% CI 0.65-2.08) compared with IVIG. Incidences of coronary artery lesions (CALs), newly developing CALs, and CAL regression did not differ between both groups. For initial treatment of KD, infliximab in addition to IVIG led to a nominally significant higher effectiveness rate (OR = 2.26, 95% CI 1.02-5.01) and a larger reduction of right coronary artery Z score (MD = -0.24, 95% CI -0.27 to -0.21) but did not show additional efficacy in improving other outcomes. The safety profile was similar between both groups. Conclusion: The meta-analysis demonstrates that infliximab alone is a well-tolerated and effective treatment for IVIG-resistant KD. The additional efficacy of infliximab to IVIG for initial treatment of KD is limited. More large and high-quality trials are needed to confirm the efficacy of infliximab, especially for intensification of primary treatment for KD. What is Known: • Infliximab is a novel monoclonal antibody specifically blocking tumor necrosis factor-alpha and is approved for treatment of several immune-mediated inflammatory disorders. • The efficacy of infliximab in treating children with Kawasaki disease is controversial. What is New: • Infliximab is an effective and safe treatment for children with refractory Kawasaki disease but adds limited efficacy to intravenous immunoglobulin for initial treatment of Kawasaki disease.
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Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis
Wang, C., Lebedeva, V., Yang, J., Anih, J., Park, L. J., Paczkowski, F., Roshanov, P. S.
Perioperative medicine (London, England). 2024;13(1):5
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Abstract
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
PICO Summary
Population
Children or adults without known inherited bleeding disorders undergoing surgery or other invasive procedures (63 randomised controlled trials, n= 4,163).
Intervention
Desmopressin administered intravenously or subcutaneously before, during, or immediately after a surgical or interventional procedure.
Comparison
Placebo, usual care, or antifibrinolytic agents.
Outcome
Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95; 95% confidence interval (CI) [0.86, 1.05]) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75; 95% CI [0.47, 1.19]) when compared to placebo or usual care. However, the authors demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units; 95% CI [-0.94, -0.15]), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI [-0.56, -0.23]), and the risk of bleeding events (2 trials, RR 0.45; 95% CI [0.24, 0.84]). The certainty of evidence of these findings was generally low.
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A systematic review of tourniquet use in paediatric orthopaedic surgery: can we extrapolate from adult guidelines?
Pintar, V., Brookes, C., Trompeter, A., Bridgens, A., Hing, C., Gelfer, Y.
EFORT open reviews. 2024;9(1):80-91
Abstract
PURPOSE Tourniquets are commonly used intraoperatively in orthopaedic surgery to control bleeding and improve visibility in the surgical field. Recent evidence has thrown into question the routine use of tourniquets in the adult population resulting in a British Orthopaedic Association standard for intraoperative use. This systematic review evaluates the evidence on the practice, benefits, and risks of the intraoperative use of tourniquets for trauma and elective orthopaedic surgery in the paediatric population. METHODS A prospectively registered systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022359048). A search of MEDLINE, Embase, the Cochrane Library and a Grey literature search was performed from their earliest record to 23 March 2023. Studies reporting tourniquet data in paediatric patients undergoing orthopaedic surgery were included. Data extracted included demographics, involved limb, trauma versus elective use, tourniquet use as primary or secondary measure, and tourniquet parameters and complications. RESULTS Thirty-nine studies were included. Tourniquet practices and information reporting varied considerably. Tourniquets were used uneventfully in the majority of patients with no specific benefits reported. Several physiological and biochemical changes as well as complications including nerve injury, compartment syndrome, skin burns, thrombosis, post-operative limb swelling, and pain were reported. CONCLUSIONS Tourniquets are routinely used in both trauma and elective paediatric orthopaedic surgery with no high-quality research affirming benefits. Severe complications associated with their use are rare but do occur. High-quality studies addressing their benefits, the exact indication in children, and the safest way to use them in this population are necessary.
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Preoperative Transfusion in Sickle Cell Disease Children Undergoing Adenotonsillectomy
Kanotra, S., Muller, S. H., Kanotra, J., Gardner, R., Kanotra, S. P.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2023;75(2):227-235
Abstract
OBJECTIVE To perform a systematic review and meta-analysis comparing two pre-operative transfusion regimens (conservative versus aggressive) in children with sickle cell disease(SCD) undergoing adenotonsillectomy in terms of post-operative complications, complications related to SCD and transfusion related complications. DATA SOURCES AND REVIEW METHODS A literature review was performed through PubMed, EMBASE, Cochrane, and Ovid databases using the following phrases: (Adenotonsillectomy OR Tonsillectomy) AND (Sickle Cell Disease OR Sickle Cell Trait). Using predetermined inclusion and exclusion criteria, seven articles were selected for systemic review and two control trials were included in meta-analysis. RESULTS Out of a total of 3,146 results, seven articles were selected for review and two controlled trials were included in the meta-analysis. There was no statistically significant difference in the rate of primary and secondary hemorrhage between the aggressive and conservative transfusion regimens (RR = 3.1, CI = 0.84-11.4, p-value = 0.089). The rate of sickle cell disease related complications including vaso-occlusive crisis and acute chest syndrome was also not statistically significant between the two transfusion groups (RR = 1.4, CI = 0.7-2.8, p-value = 0.339). Even though, the transfusion related complications did not reach statistical significance, there was a higher complication rate in the group receiving aggressive blood transfusion. CONCLUSION In SCD children undergoing adenotonsillectomy, an aggressive transfusion regimen that focuses on reducing the Hemoglobin S ratio to below 30% has not been shown to be more effective in reducing post-operative complications when compared to a conservative transfusion regimen. Therefore, it is reasonable to utilize a conservative transfusion regimen, thereby reducing the transfusion-associated risks.
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Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: A systematic review and meta-analyses
Abdellatif, M., Abozaid, A. A. F., Shah, P. S., Dhouibi, N., Nguyen-Khac, T., Khleif, R., Luu, M. N., Quyen, D. K., Mohareb, A., Vaghela, G., et al
Canadian journal of physiology and pharmacology. 2023
Abstract
Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence's certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dl) (TSB) was significant at 12, 24, 36, 48 and 72 hours with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN+PT group had a shorter duration of phototherapy (MD -14.36 hours; 95% CI -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger RCTs are needed for confirmation of these results.
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Endoscopic Primary Prophylaxis to Prevent Bleeding in Children with Esophageal Varices: A Systematic Review and Meta-Analysis
Alatas, F. S., Monica, E., Ongko, L., Kadim, M.
Pediatric gastroenterology, hepatology & nutrition. 2023;26(5):231-238
Abstract
PURPOSE This systematic review and meta-analysis aimed to compare endoscopy as primary versus secondary prophylaxis to prevent future bleeding in children with esophageal varices. METHODS A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was conducted using the Scopus, PubMed, and Cochrane databases for relevant studies on the outcome of rebleeding events after endoscopy in primary prophylaxis compared to that in secondary prophylaxis. The following keywords were used: esophageal varices, children, endoscopy, primary prophylaxis and bleeding. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale and statistically analyzed using RevMan 5.4 software. RESULTS A total of 174 children were included from four eligible articles. All four studies were considered of high-quality based on the Newcastle-Ottawa Quality Assessment Scale. Patients who received primary prophylaxis had 79% lower odds of bleeding than those who received secondary prophylaxis (odds ratio, 0.21; 95% confidence interval [CI], 0.07-0.66; I(2)=0%, p=0.008). Patients in the primary prophylaxis group underwent fewer endoscopic procedures to eradicate varices than those in the secondary prophylaxis group, with a mean difference of 1.73 (95% CI, 0.91-2.56; I(2)=62%, p<0.0001). CONCLUSION Children with high-risk varices who underwent primary prophylaxis were less likely to experience future bleeding episodes and required fewer endoscopic procedures to eradicate the varices than children who underwent secondary prophylaxis.
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Safety and efficacy of pharmacological approaches available for multisystem inflammatory syndrome in children (MIS-C): a systematic review
Velusamy, Y., Vivekanandan, G., Romli, M. H., Shankar, A., Karuppiah, T., Yubbu, P.
The Turkish journal of pediatrics. 2023;65(5):719-738
Abstract
BACKGROUND To describe the existing pharmacological managements for Multisystem Inflammatory Syndrome in Children (MIS-C) in a systematic way, to identify the available pharmacological managements in MIS-C, evaluate its safety and efficacy and identify the best treatment procedures for practice recommendation. METHODS A systematic search using six databases was conducted on August 18, 2021, updated in January 26th 2023. Terminologies that were used in this search are children, MIS-C/PIMS and SARS-CoV-2. A PRISMA flow diagram was used to report the study selection process. Quality analysis was done based on NOS and GRADE tools. Data synthesis was conducted by extracting the information on drugs used, efficacy and side effects. RESULTS From the 32 articles included, a total of 2331 children with MIS-C were studied. The main pharmacological approaches were immunomodulatory therapy, i.e., intravenous immunoglobulin (IVIG) (77.3%), steroids (60.5%), and a combination of IVIG and steroids (41.3%). IVIG and steroids were found to be potentially effective and safe treatments for MIS-C. Combination of IVIG and steroids was found favorable in severe cases with higher recovery rate. Refractory treatments include second dose of initial treatment and biological response modifier drugs like anakinra, tocilizumab, infliximab. A small number of studies investigating supportive treatment consisted of vasoactive, inotropic and anticoagulation. The mortality rate was 1.28% and only three studies reported side effects from the treatment. Evidence of outcome from GRADE were mostly at moderate, low and very low levels. CONCLUSIONS This review provides preliminary evidence to support the current standard treatment practices in managing MIS-C pharmacologically. However, comprehensive investigation is required using clinical trials to provide stronger outcome evidence.
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Frequency of red blood cell transfusions in preterm neonates in Brazil: A systematic review and meta-analysis
Valete, C. O. S., Angelica Luiz Ferreira, E., Montenegro, C. P., Pilati, M. C. A., Rodrigues Wilde, M. O. D., Witkowski, S. M.
Vox sanguinis. 2023
Abstract
BACKGROUND AND OBJECTIVES Red blood cell transfusions are frequent in preterm neonates. The proportion of preterm neonates transfused in Brazil remains unknown. We systematically reviewed the literature to estimate the frequency of red blood cell transfusions in preterm neonates in Brazil. MATERIALS AND METHODS The LILACS, EMBASE, Cochrane, SciELO, MEDLINE (PubMed), Web of Science, Scopus, BDTD and 27 national university institutional databases were searched for studies that analysed red blood cell transfusion in preterm neonates in Brazil without period restriction. The Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed, and the GRADE methodology was applied. A random-effects model along with the restricted maximum likelihood method was used, and the Freeman-Tukey transformed proportion was used to estimate effect size. RESULTS Nine studies, representing 6548 preterm neonates, were included in the qualitative and quantitative analyses. The mean gestational age ranged from 26.0 to 31.6 weeks. Most of the studies were from the Southeast region. The pooled estimated frequency of red blood cell transfusions was 58.0% (95% confidence interval = 52.0%-64.0%, p < 0.001) with low certainty. There was statistically significant heterogeneity among studies (I(2) = 92.5%, p < 0.001). CONCLUSION In this current meta-analysis of the evidence available, which included moderate and extremely preterm neonates, the observed frequency of red blood cell transfusions in preterm neonates in Brazil was 58.0% and this estimate can help health programming. Some Brazilian regions were not included in this study, and further research is needed to provide a more representative overview of Brazil.
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10.
Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature
Karapati E, Sokou R, Iliodromiti Z, Tsaousi M, Sulaj A, Tsantes AG, Petropoulou C, Pouliakis A, Tsantes AE, Boutsikou T, et al
Seminars in thrombosis and hemostasis. 2023
Abstract
Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.