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Journal of Neurotrauma Nov 2023Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last... (Review)
Review
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.
Topics: Adult; Child; Humans; Young Adult; Anticoagulants; Brain Injuries, Traumatic; Erythrocyte Transfusion; Hypopituitarism; Venous Thromboembolism; Practice Guidelines as Topic
PubMed: 37341019
DOI: 10.1089/neu.2023.0149 -
European Journal of Pediatrics Aug 2023Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Infant, Newborn; Humans; Infant, Premature; Hemorrhage; Enterocolitis, Necrotizing; Thrombocytopenia; Sepsis
PubMed: 37258776
DOI: 10.1007/s00431-023-05031-y -
PharmacoEconomics Aug 2023Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed...
OBJECTIVES
Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia.
METHODS
Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist.
RESULTS
Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%).
CONCLUSIONS
Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.
Topics: Adult; Humans; Thrombopoietin; Cost-Benefit Analysis; Thrombocytopenia; Hemorrhage; Quality-Adjusted Life Years
PubMed: 37145291
DOI: 10.1007/s40273-023-01271-w -
Whole blood transfusion in the treatment of acute hemorrhage, a systematic review and meta-analysis.The Journal of Trauma and Acute Care... Aug 2023Whole blood (WB) transfusion received renewed interest after recent armed conflicts. The effectiveness as compared with blood component transfusion (BCT) is, however,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whole blood (WB) transfusion received renewed interest after recent armed conflicts. The effectiveness as compared with blood component transfusion (BCT) is, however, still topic of debate. Therefore, this study investigated the effect of WB ± BCT as compared with BCT transfusion on survival in trauma patients with acute hemorrhage.
METHODS
Studies published up to January 16, 2023, including patients with traumatic hemorrhage comparing WB ± BCT and BCT were included in meta-analysis. Subanalyses were performed on the effectiveness of WB in the treatment of civilian or military trauma patients, patients with massive hemorrhage and on platelet (PLT)/red blood cell (RBC), plasma/RBC and WB/RBC ratios. Methodological quality of studies was interpreted using the Cochrane risk of bias tool. The study protocol was registered in PROSPERO under number CRD42022296900.
RESULTS
Random effect pooled odds ratio (OR) for 24 hours mortality in civilian and military patients treated with WB as compared with BCT was 0.72 (95% confidence interval [CI], 0.53-0.97). In subanalysis of studies conducted in civilian setting (n = 20), early (4 hours, 6 hours, and emergency department) and 24 hours mortality was lower in WB groups compared with BCT groups (OR, 0.65; 95% CI, 0.44-0.96 and OR, 0.71; 95% CI, 0.52-0.98). No difference in late mortality (28 days, 30 days, in-hospital) was found. In military settings (n = 7), there was no difference in early, 24 hours, or late mortality between groups. The WB groups received significant higher PLT/RBC ( p = 0.030) during early treatment and significant higher PLT/RBC and plasma/RBC ratios during 24 hours of treatment ( p = 0.031 and p = 0.007). The overall risk of bias in the majority of studies was judged as serious due to serious risk on confounding and selection bias, and unclear information regarding cointerventions.
CONCLUSION
Civilian trauma patients with acute traumatic hemorrhage treated with WB ± BCT as compared to BCT had lower odds on early and 24-hour mortality. In addition, WB transfusion resulted in higher PLT/RBC and plasma/RBC ratios.
LEVEL OF EVIDENCE
Systematic Review and Meta-Analysis; Level III.
Topics: Humans; Blood Transfusion; Hemorrhage; Blood Component Transfusion; Resuscitation; Emergency Service, Hospital; Wounds and Injuries
PubMed: 37125904
DOI: 10.1097/TA.0000000000004000 -
World Journal of Emergency Surgery :... Mar 2023The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations.
METHODS AND ANALYSIS
In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials.
RESULTS
Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64-2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI - 0.99-0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07-5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment.
CONCLUSIONS
The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.
Topics: Humans; Fibrinogen; Hemorrhage; Hemostatics; Blood Transfusion; Elective Surgical Procedures
PubMed: 36998084
DOI: 10.1186/s13017-023-00497-5 -
International Journal of Colorectal... Mar 2023To analyse the safety and effectiveness of platelet-rich plasma (PRP) in anal fistula patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To analyse the safety and effectiveness of platelet-rich plasma (PRP) in anal fistula patients.
METHODS
Online databases including PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to December 5, 2022, for eligible studies about evaluating the efficacy of platelet-rich plasma (PRP) in treating anal fistula. Literature search, screening, data extraction, and quality assessment were carried out by two independent investigators. The overall cure rate, the complete cure rate, the recurrence rate, and the adverse event rate with their 95% confidence intervals (95% CI) were the primary calculation indexes. Subgroup analyses were conducted primarily according to whether PRP was combined with other treatments. Softwares of MedCalc 18.2 and Review Manager 5.3 were used for meta-analysis.
RESULTS
A total of 14 studies with 514 patients were included in the meta-analysis. The overall cure rate of 14 studies was 72.11% (95% CI 0.64-0.79). The cure rate of PRP alone was 62.39% (95% CI 0.55-0.69). The combined cure rate of PRP with other treatments was 83.12% (95% CI 0.77-0.88). The cure rate of interventions involving PRP were superior to the cure rate of surgery methods without using PRP significantly in the 4 randomized controlled studies (RR = 1.30, 95% CI 1.10-1.54, p = 0.002). The complete cure rate of the 8 studies was 66.37% (95% CI 0.52-0.79). The recurrence rate of the 12 studies was 14.84% (95% CI 0.08-0.24). The adverse event rate of the 12 studies was 6.31% (95% CI 0.02-0.12).
CONCLUSION
PRP showed favorable safety and effectiveness in the treatment of anal fistula, especially combined with other treatment procedures.
Topics: Humans; Platelet-Rich Plasma; Research Design; Rectal Fistula; Treatment Outcome
PubMed: 36905475
DOI: 10.1007/s00384-023-04367-z -
Transfusion and Apheresis Science :... Jun 2023Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE sometimes cannot be implemented. The aim of this study was to systematically review patients with a first TTP episode who were treated without TPE.
METHOD
The PubMed, Embase, Web of Science and Cochrane Library databases were searched by two investigators independently to collect case reports and clinical studies on TTP patients treated without TPE. After removing duplicate records and records that did not meet the inclusion criteria, the patients' data of eligible studies, including the basic characteristics, treatment regimens, and outcomes were extracted for further analysis.
RESULTS
A total of 5338 potentially relevant original studies were identified, from which 21 studies, including 14 cases, 3 case series and 4 retrospective studies, met eligibility requirements and were included. Treatment regimens in the absence of TPE were found to vary based on individual information. Most patients recovered, with normal platelet counts and ADAMT13 activity at discharge. In the meta-analysis of retrospective studies, the TPE-free group had no higher mortality than the TPE-treated group.
CONCLUSION
Our study shows that TPE-free treatment may not increase the mortality of TTP patients, which provides a new treatment concept for patients with first episodes of TTP. However, the current evidence is not high due to the lack of randomized controlled trials, so more well-designed prospective clinical trials are warranted to investigate the safety and efficacy of TPE-free treatment regimens in TTP patients.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Prospective Studies; Treatment Outcome; Plasma Exchange
PubMed: 36878741
DOI: 10.1016/j.transci.2023.103661 -
Seminars in Thrombosis and Hemostasis Mar 2024Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including...
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 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.
Topics: Female; Infant, Newborn; Humans; Hemostatics; Fetal Growth Retardation; Hemostasis; Blood Coagulation Disorders; Hemorrhage; Thrombelastography; Thrombosis; Thrombocytopenia
PubMed: 36807290
DOI: 10.1055/s-0043-1762893 -
Tropical Medicine & International... Apr 2023Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different PIMs, according to the blood product they are used on and the arbovirus targeted.
METHODS
Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main PIMs (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods.
RESULTS
We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load-mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating Chikungunya virus, Dengue virus and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).
CONCLUSION
Not all PIMs achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the PIMs. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated PIMs and be logistically prepared to implement these techniques quickly.
Topics: Humans; Arboviruses; Detergents; Polyamines; Zika Virus; Riboflavin; Zika Virus Infection
PubMed: 36806816
DOI: 10.1111/tmi.13863 -
Frontiers in Endocrinology 2023The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.
OBJECTIVE
The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.
METHODS
The data of patients with antithyroid drug-induced aplastic anemia were retrieved from PubMed and Wanfang Medical Network databases from 1992 to August 2022. The clinical characteristics, such as age distribution, gender tendency, common symptoms, blood cell count, bone marrow features, treatment strategy, and prognosis, were analyzed.
RESULTS
A total of 17 cases (male:female = 1:16) had been retrieved. Patients' age ranged from 16 to 74 years (median 50 years). Among them, 82.3% (14/17) of the patients were administered methimazole (MMI), and 78.6% of them had MMI ≥30 mg/day. In addition, 88.2% (15/17) of the patients had sore throat and fever, and 47.1% (8/17) of the patients had hemorrhagic symptoms. Aplastic anemia occurred within 6 months after initiation of the antithyroid therapy in 94.1% of the patients. Agranulocytosis (94.1%) was the most common and earliest blood cell change, and 47.1% of the patients experienced progressive platelet decline during the treatment process. The treatments include timely withdrawal of antithyroid drugs, broad-spectrum antibiotics, granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF), glucocorticoids and other immunosuppressive agents, and supportive treatments such as erythrocyte transfusion and platelet transfusion. Moreover, 70.6% of the patients had complete or near-complete remission within 8 days to 6 weeks.
CONCLUSION
Aplastic anemia is a rare and serious adverse reaction of antithyroid drugs, which is more common in women. It usually occurs during early treatment with high-dose antithyroid drugs. Most patients have a good prognosis after timely drug ceasing and appropriate treatment.
Topics: Female; Humans; Male; Adolescent; Young Adult; Adult; Middle Aged; Aged; Antithyroid Agents; Anemia, Aplastic; Methimazole; Bone Marrow; Glucocorticoids
PubMed: 36777352
DOI: 10.3389/fendo.2023.1064723