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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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Management of non-compressible torso hemorrhage of the abdomen in civilian and military austere environments: a scoping review
Adams, D., McDonald, P. L., Holland, S., Merkle, A. B., Puglia, C., Miller, B., Allison, D. D., Moussette, C., Souza, C. J., Nunez, T., et al
Trauma surgery & acute care open. 2024;9(1):e001189
Abstract
BACKGROUND Non-compressible abdominal hemorrhage (NCAH) is the leading cause of potentially preventable deaths in both civilian and military austere environments, and an improvement in mortality due to this problem has not been demonstrated during the past quarter century. Several innovations have been developed to control hemorrhage closer to the point of injury. OBJECTIVE This review assessed NCAH interventions in civilian and military settings, focusing on austere environments. It identified innovations, effectiveness, and knowledge gaps for future research. METHODOLOGY The Joanna Briggs Institute for Evidence Synthesis methodology guided this scoping review to completion. Studies evaluating NCAH with human participants in civilian and military austere environments that were eligible for inclusion were limited to English language studies published between December 1990 and January 2023. The PCC (Participant, Concept, Context) framework was used for data synthesis. Deductive and inductive thematic analyses were used to assess the literature that met inclusion criteria, identify patterns/themes to address the research questions and identify common themes within the literature. A stakeholder consultation was conducted to review and provide expert perspectives and opinions on the results of the deductive and inductive thematic analyses. RESULTS The literature search identified 868 articles; 26 articles met the inclusion criteria. Textual narrative analysis of the 26 articles resulted in the literature addressing four main categories: NCAH, penetrating abdominal trauma, resuscitative endovascular balloon occlusion of the aorta (REBOA), and ResQFoam. The deductive thematic analysis aimed to answer three research questions. Research question 1 addressed the effectiveness of REBOA, damage control resuscitation, and damage control surgery in managing NCAH in austere environments. No effectiveness studies were found on this topic. Research question 2 identified three knowledge gaps in NCAH management in austere environments. The analysis identified early hemorrhage control, prehospital provider decision-making ability, and REBOA implementation as knowledge gaps in NCAH. Research question 3 identified five innovations that may affect the management of NCAH in the future: transport of patients, advanced resuscitative care, expert consultation, REBOA implementation, and self-expanding foam implementation. The inductive thematic analysis resulted in four recurrent themes from the literature: prehospital care, decision-making, hemorrhage control, and mortality in NCAH. During the stakeholders' consultation, the results of the deductive and inductive thematic analyses were reviewed and agreed on by the stakeholders. Special emphasis and discussion were given to prehospital management, expert opinions in the prehospital environment, decision-making in the prehospital environment, transport and resuscitation in the prehospital setting, REBOA, alternative discussion for research, and research gaps. CONCLUSION NCAH is still a significant cause of preventable death in both military and civilian austere environments, even with ongoing research and interventions aimed at extending survival in such conditions. This scoping review has identified several potential concepts that could reduce the mortality associated with a preventable cause of death due to hemorrhage in austere environments.
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Tranexamic acid for the prevention and treatment of postpartum hemorrhage in resource-limited settings: a literature review
Gedeno Gelebo, K., Mulugeta, H., Mossie, A., Geremu, K., Darma, B.
Annals of medicine and surgery (2012). 2024;86(1):353-360
Abstract
INTRODUCTION Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. Early recognition and appropriate treatment are crucial for managing postpartum haemorrhage. OBJECTIVES This literature review aimed to evaluate the efficacy of tranexamic acid in the prevention and treatment of postpartum haemorrhage in resource-limited settings. SEARCH METHODS This literature review was conducted based on the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. A computerized systematic search of the MEDLINE (PubMed), Google Scholar, and Cochrane databases using a combination of the following Medical Subject Headings (MeSH) terms for PubMed: [(obstetric haemorrhage OR postpartum haemorrhage OR massive obstetric haemorrhage) AND (tranexamic acid OR antifibrinolytic drugs) AND (prophylaxis OR prevention) AND (management OR treatment) AND (resource-limited settings OR resource-limited area OR developing countries)] to find articles published in English since 2010. SELECTION CRITERIA Studies on the obstetric population who underwent vaginal or caesarean delivery, comparing the use of tranexamic acid versus placebo (or no treatment) for treatment (or prevention) of postpartum haemorrhage with the outcome of postpartum haemorrhage rate, blood transfusion requirements, uterotonics requirements, hysterectomy, or mortality were included. RESULT In total, 5315 articles were identified. Following the elimination of duplicates, the methodological quality of 15 studies was evaluated independently, with eligibility determined based on the inclusion and exclusion criteria, as well as outcome variables. Finally, eight articles were included in the review. CONCLUSION This review provides evidence that the administration of tranexamic acid has the potential to decrease the need for blood transfusion, incidence of postpartum haemorrhage, demand for supplementary uterotonics, and maternal morbidity and mortality with marginal adverse effects. Healthcare systems must develop and implement interventions that involve the use of tranexamic acid for the treatment of postpartum haemorrhage in resource-limited settings.
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Intravenous iron versus blood transfusion for postpartum anemia: a systematic review and meta-analysis
Caljé, E., Groom, K. M., Dixon, L., Marriott, J., Foon, R., Oyston, C., Bloomfield, F. H., Jordan, V.
Systematic reviews. 2024;13(1):9
Abstract
BACKGROUND Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses. METHODS A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115). RESULTS Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I(2) = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I(2) = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I(2) = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I(2) = 84%). The overall quality of the evidence was low-moderate. DISCUSSION For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.
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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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Editor's Choice
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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Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis
Totoki, T., Makino, Y., Yamakawa, K., Koami, H., Wada, T., Ito, T., Iba, T.
Thrombosis journal. 2024;22(1):10
Abstract
BACKGROUND Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model. METHOD We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study. RESULTS We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I(2) values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55-2.23], I(2) value 55%). CONCLUSIONS Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results. TRIAL REGISTRATION This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID 000049820).
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Comparison of the effect of open-box versus closed-box prostheses on blood loss following total knee arthroplasty: a meta-analysis
Elhalag, R. H., Dean, Y. E., Hamdy, A., Hadhoud, A. M., Chébl, P., Shah, J., Gawad, M., Motawea, K. R.
Annals of medicine and surgery (2012). 2024;86(2):1021-1028
Abstract
PURPOSE Postoperative blood loss is a common complication following total knee arthroplasty (TKA). The authors aimed to analyze the significance of open versus closed-box prostheses in reducing blood loss after TKA. METHODS PubMed, Cochrane, Scopus, and Web of Science were searched. Observational studies and clinical trials comparing the effect of open-box versus closed-box prostheses on blood loss following TKA were included. The primary outcome was total blood loss following TKA. Secondary outcomes included average transfused units and total operation time. Continuous data were represented as mean difference (MD) and CI, while dichotomous data were presented as odds ratio (OR) and CI. RevMan software version 5.4 was used to conduct the analysis. RESULTS Four studies with a total number of 687 patients were included. The pooled analysis showed a statistically significant association between closed-box and decreased total blood loss following TKA compared with open-box (MD=173.19, 95% CI=88.77-257.61, P value <0.0001). Similar findings were reported in unilateral TKA (MD=190.63, 95% CI=70.91-310.35, P value=0.002), and bilateral TKA (MD=160.79, 95% CI=61.70-359.86, P value=0.001). There was no significant difference between open and closed-box regarding average transfused units (MD=0.02, 95% CI=-0.07-0.11, P value=0.68), blood transfusion rate (OR=1.38, 95% CI=0.85-2.26, P value=0.20), length of stay (MD=0.06, 95% CI=-0.27 to 0.38, P value=0.74), and total operation time (MD=1.08, 95% CI=-4.62 to 6.79, P value=0.71). CONCLUSION Closed-box reduces the total blood loss following unilateral and bilateral TKA. More studies are warranted to explore the benefits of Closed-box in patients with high bleeding susceptibility.
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Reported outcomes in patients with iron deficiency or iron deficiency anemia undergoing major surgery: a systematic review of outcomes
Stangl, S., Popp, M., Reis, S., Sitter, M., Saal-Bauernschubert, L., Schießer, S., Kranke, P., Choorapoikayil, S., Weibel, S., Meybohm, P.
Systematic reviews. 2024;13(1):5
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Editor's Choice
Abstract
BACKGROUND Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia. METHODS We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted. RESULTS Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77%) and "need for further resources" (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting. CONCLUSION This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020214247.
PICO Summary
Population
Patients with iron deficiency or iron deficiency anaemia undergoing major surgery (13 studies: 5 randomised controlled trials and 8 observational studies).
Intervention
Systematic review to identify and appraise outcomes reported for preoperative or perioperative treatment of iron deficiency, with or without anemia.
Comparison
Outcome
Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by ‘adverse event’ (77%) and ‘need for further resources’ (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting.
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Esophageal Stent in Acute Refractory Variceal Bleeding: A Systematic Review and a Meta-Analysis
Songtanin, B., Kahathuduwa, C., Nugent, K.
Journal of clinical medicine. 2024;13(2)
Abstract
Background: Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. Aim: To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. Methods: A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Results: Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, I(2) = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, I(2) = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, I(2) = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, I(2) = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, I(2) = 34). Conclusions: SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.
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Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials
Shen, N., Qiao, J., Jiang, Y., Yan, J., Wu, R., Yin, H., Zhu, S., Li, J.
Biomedical reports. 2024;20(3):44
Abstract
Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.