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1.
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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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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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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Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants
Romantsik O, Smit E, Odd DE, Bruschettini M
The Cochrane database of systematic reviews. 2023;3(3):Cd001691
Abstract
BACKGROUND Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013. OBJECTIVES To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL and clinical trial registries in January 2022. A new, more sensitive search strategy was developed, and searches were conducted without date limits. SELECTION CRITERIA We included randomised controlled trials (RCTs) or quasi-RCTs in which phenobarbital was given within the first 24 hours of life to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birth weight below 1500 g or respiratory failure. Phenobarbital was compared to no intervention or placebo. We excluded infants with serious congenital malformations. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were all grades of IVH and severe IVH (i.e. grade III and IV); secondary outcomes were ventricular dilation or hydrocephalus, hypotension, pneumothorax, hypercapnia, acidosis, mechanical ventilation, neurodevelopmental impairment and death. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 10 RCTs (792 infants). The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH of any grade compared with control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.84 to 1.19; risk difference (RD) 0.00, 95% CI -0.06 to 0.07; I² for RD = 65%; 10 RCTs, 792 participants; low certainty evidence) and in severe IVH (RR 0.88, 95% CI 0.64 to 1.21; 10 RCTs, 792 participants; low certainty evidence). The evidence is very uncertain about the effect of phenobarbital on posthaemorrhagic ventricular dilation or hydrocephalus (RR 0.62, 95% CI 0.31 to 1.26; 4 RCTs, 271 participants; very low certainty evidence), mild neurodevelopmental impairment (RR 0.57, 95% CI 0.15 to 2.17; 1RCT, 101 participants; very low certainty evidence), and severe neurodevelopmental impairment (RR 1.12, 95% CI 0.44 to 2.82; 2 RCTs, 153 participants; very low certainty evidence). Phenobarbital may result in little to no difference in death before discharge (RR 0.88, 95% CI 0.64 to 1.21; 9 RCTs, 740 participants; low certainty evidence) and mortality during study period (RR 0.98, 95% CI 0.72 to 1.33; 10 RCTs, 792 participants; low certainty evidence) compared with control. We identified no ongoing trials. AUTHORS' CONCLUSIONS The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.
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Eltrombopag for Adults and Children with Immune-Refractory Thrombocytopenic Purpura: A Systematic Review
de Barros Torelli, D. F. H., Oliveira, C. B. S., Nai, G. A., Trindade, E. M., Prestes-Carneiro, L. E.
Journal of clinical medicine. 2023;12(12)
Abstract
Eltrombopag is an agonist that binds to the membrane-bound domain of the thrombopoietin receptor used in immune thrombocytopenic purpura (ITP). We conducted a meta-analysis of randomized controlled trials to assess the efficacy and safety of eltrombopag in adults and children with refractory ITP. Adults who received eltrombopag had a significantly better platelet response (relative risk [RR], 3.65; 95% confidence interval [CI], 2.39-5.55), but there were no differences in the incidence of bleeding (RR, 0.8; 95% CI, 0.52-1.22) and adverse effects (RR, 0.99; 95% CI, 0.55-1.78) compared with the placebo. In children, there was no difference between eltrombopag and placebo for a platelet response >50,000/mm(3) (RR, 3.93; 95% CI, 0.56-27.79) and the number of adverse events (RR, 0.99; 95% CI, 0.25-1.49); however, a lower incidence of bleeding was observed (RR, 0.47; 95% CI, 0.27-0.83). Treatment with eltrombopag protected adults and children from severe disease and death.
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Efficacy and safety of pharmacological interventions for managing sickle cell disease in children and adolescents: protocol for a systematic review with network meta-analysis
Tonin, F. S., Ginete, C., Fernandez-Llimos, F., Ferreira, J., Delgadinho, M., Brito, M.
BMJ open. 2023;13(2):e064872
Abstract
INTRODUCTION Sickle cell disease (SCD), an inherited haemoglobinopathy, has important impact on morbidity and mortality, especially in paediatrics. Previous systematic reviews are limited to adult patients or focused only on few therapies. We aim to synthesise the evidence on efficacy and safety of pharmacological interventions for managing SCD in children and adolescents. METHODS AND ANALYSIS This systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9). We will follow international recommendations on conduction and report of systematic reviews and meta-analyses. Searches will be conducted in PubMed, Scopus and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival and adverse events. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with surface under the cumulative ranking curve analyses. Different statistical methods and models will be tested. Dichotomous outcomes will be reported as OR, risk ratio or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION This study refers to a systematic review, so no ethics approval is necessary. We intent to publish our findings in international, peer-reviewed journal. Data will also be presented to peers in scientific events. Additionally, the results obtained in this study may contribute towards the update of therapeutic guidelines and for the development of health policies for SCD. PROSPERO REGISTRATION NUMBER CRD42022328471.
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Platelet transfusions in preterm infants: current concepts and controversies-a systematic review and meta-analysis
Ribeiro HS, Assunção A, Vieira RJ, Soares P, Guimarães H, Flor-de-Lima F
European journal of pediatrics. 2023
Abstract
Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.
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The efficacy and the safety of eltrombopag in pediatric patients with severe aplastic anemia: a systematic review
Marrapodi MM, Mascolo A, Roberti D, Martino MD, Rafaniello C, Riccardi C, Rossi F
Frontiers in pediatrics. 2023;11:1149718
Abstract
BACKGROUND Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited. METHODS AND FINDINGS We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population. CONCLUSION Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.
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The effect of perioperative antithrombin supplementation on blood conservation and postoperative complications after cardiopulmonary bypass surgery: A systematic review, meta-analysis and trial sequential analysis
Li, T., Bo, F., Meng, X., Wang, D., Ma, J., Dai, Z.
Heliyon. 2023;9(11):e22266
Abstract
STUDY OBJECTIVE Antithrombin (AT) activity is reduced during cardiopulmonary bypass (CPB) surgery. Guidelines has demonstrated that perioperative AT supplementation contributed to blood conservation and prevent perioperative thrombotic complications and target organ injury owing to its role in reducing thrombin generation. But these recommends is lack of support of meta-analysis in the guidelines. This meta-analysis aims to include all the relevant randomized controlled trails (RCT) on patients who experienced cardiac surgeries with CPB and investigate the effect of perioperative AT on blood conservation and complications after cardiac surgery. METHODS Standard published RCTs were searched from bibliographic databases to identify all evidence reporting perioperative AT supplementation for patients undergoing cardiovascular surgeries. The primary outcome was postoperative blood loss, the secondary outcomes were blood component transfusion (red blood cell (RBC), fresh frozen plasma (FFP), platelet and autologous blood), postoperative morbidity and in hospital mortality. The relative risk (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes were estimated using a random-effects model. Trial sequential analysis (TSA) was performed using TSA software 0.9.5.10. RESULTS 13 RCTs with 996 participants undergoing different cardiovascular surgeries were included. Meta-analysis showed AT did not decrease postoperative blood loss (SMD -0.01, 95%CI -0.2 to 0.19). Subgroup analysis showed the effect of AT on postoperative blood loss was not associated with age, RCT type, surgery type, injection time of AT and AT deficiency. TSA further suggested that no additional studies were required for the stable result. Perioperative AT also did not reduce RBC ((SMD 0.10, 95%CI -0.66 to 0.85), (RR 0.99, 95%CI 0.83 to 1.19)), FFP ((SMD 0.11, 95%CI -0.19 to 0.41), (RR 1.30, 95%CI 0.90 to 1.87)), platelet (RR 1.10, 95%CI 0.83 to 1.46) and autologous blood (SMD 0.46, 95%CI -0.12 to 1.8504) transfusions. Perioperative AT significantly increased in hospital mortality (RR 2.53, 95%CI 1.02 to 6.28) and acute kidney injury (AKI) (RR 3.72, 95%CI 1.73 to 8.04) incidence. There was no significant difference in postoperative reexploration, thromboembolism, ECMO/IABP support, and stroke incidence between AT and non-AT group. CONCLUSIONS With the improvement of AT level and heparin sensitivity, perioperative AT has no significant effect on blood conservation. And it is noteworthy that the treatment increased in hospital mortality and the incidence of AKI after cardiac surgery.