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The Impact of Time to Hemostatic Intervention and Delayed Care for Patients with Traumatic Hemorrhage: A Systematic Review
Lamb T, Tran A, Lampron J, Shorr R, Taljaard M, Vaillancourt C
The journal of trauma and acute care surgery. 2023
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Editor's Choice
Abstract
BACKGROUND Uncontrolled bleeding is a common cause of preventable mortality in trauma. While intuitive that delays to hemostasis may lead to worse outcomes, the impacts of these delays remain incompletely explored. This systematic review aimed to characterize the extant definitions of delayed hemostatic intervention and to quantify the impacts of delays on clinical outcomes. METHODS We searched EMBASE, MEDLINE, and Web of Science from inception to August 2022. Studies defining "delayed intervention" and those comparing times to intervention among adults presenting to hospital with blunt or penetrating injuries who required major hemostatic intervention were eligible. The co-primary outcomes were mortality and the definition of delay to hemostasis employed. Secondary outcomes included units of packed red blood cells received, length of stay in hospital, and length of stay in intensive care. RESULTS We identified 2,050 studies, with 24 studies including 10,168 patients meeting inclusion criteria. The majority of studies were retrospective observational cohort studies and most were at high risk of bias. A variety of injury patterns and hemostatic interventions were considered, with 69.6% of studies reporting a statistically significant impact of increased time to intervention on mortality. Definitions of delayed intervention ranged from ten minutes to four hours. Conflicting data were reported for impact of time on receipt of blood products, while one study found a significant impact on intensive care length of stay. No studies assessed length of stay in hospital. CONCLUSIONS The extant literature is heterogeneous with respect to injuries included, methods of hemostasis employed, and durations of delay examined. While the majority of the included studies demonstrated a statistically significant relationship between time to intervention and mortality, an evidence-informed definition of delayed intervention for bleeding trauma patients at large has not been solidified. Additional, standardized research is needed to establish targets which could reduce morbidity and mortality. LEVEL OF EVIDENCE Level IV, Systematic Review.
PICO Summary
Population
Patients with traumatic haemorrhage (24 studies, n= 10,168).
Intervention
Systematic review to characterize the extant definitions of delayed haemostatic intervention and to quantify the impacts of delays on clinical outcomes.
Comparison
Outcome
The majority of studies were retrospective observational cohort studies and most were at high risk of bias. A variety of injury patterns and haemostatic interventions were considered, with 69.6% of studies reporting a statistically significant impact of increased time to intervention on mortality. Definitions of delayed intervention ranged from ten minutes to four hours. Conflicting data were reported for impact of time on receipt of blood products, while one study found a significant impact on intensive care length of stay. No studies assessed length of stay in hospital.
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Comparison of anticoagulation monitoring strategies for adults supported on extracorporeal membrane oxygenation: A systematic review
Sun J, Ma Y, Su W, Miao H, Guo Z, Chen Q, Zhang Y, Ma X, Chen S, Ding R
Heart & lung : the journal of critical care. 2023;61:72-83
Abstract
BACKGROUND Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear. OBJECTIVES This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO. METHODS The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. RESULTS Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion. CONCLUSION Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.
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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.
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Predictive value of tachycardia for mortality in trauma-related haemorrhagic shock: a systematic review and meta-regression
Jávor, P., Hanák, L., Hegyi, P., Csonka, E., Butt, E., Horváth, T., Góg, I., Lukacs, A., Soós, A., Rumbus, Z., et al
BMJ open. 2022;12(10):e059271
Abstract
OBJECTIVES Heart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma. DESIGN This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. DATA SOURCES EMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020. ELIGIBILITY CRITERIA Papers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered. DATA EXTRACTION AND SYNTHESIS Data extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products. RESULTS From a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate. CONCLUSIONS In accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians.
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Predictors of transfusion in trauma and their utility in the prehospital environment: a scoping review
Yin G, Radulovic N, O'Neill M, Lightfoot D, Nolan B
Prehospital emergency care. 2022;:1-25
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Editor's Choice
Abstract
Background: Hemorrhage is a leading cause of preventable mortality from trauma, necessitating resuscitation through blood product transfusions. Early and accurate identification of patients requiring transfusions in the prehospital setting may reduce delays in time to transfusion upon arrival to hospital, reducing mortality. The purpose of this study is to characterize existing literature on predictors of transfusion and analyze their utility in the prehospital context.Objectives: The objectives of this study are to characterize the existing quantity and quality of literature regarding predictor scores for transfusion in injured patients, and to analyse the utility of predictor scores for massive transfusions in the prehospital setting and identify prehospital predictor scores for future research.Methods: A search strategy was developed in consultation with information specialists. A literature search of OVID MEDLINE from 1946 to present was conducted for primary studies evaluating the predictive ability of scoring systems or single variables in predicting transfusion in all trauma settings.Results: Of the 5824 studies were identified, 5784 studies underwent title and abstract screening, 94 studies underwent full text review, and 72 studies were included in the final review. We identified 16 single variables and 52 scoring systems for predicting transfusion. Amongst single predictor variables, fluids administered and systolic blood pressure had the highest reported sensitivity (100%) and specificity (89%) for massive transfusion protocol (MTP) activation respectively. Amongst scoring systems for transfusion, the Shock Index and Modified Shock Index had the highest reported sensitivity (96%), while the Pre-arrival Model had the highest reported specificity (95%) for MTP activation. Overall, 20 scores were identified as being applicable to the prehospital setting, 25 scores were identified as being potentially applicable, and seven scores were identified as being not applicable.Conclusions: We identified an extensive list of predictive single variables, validated scoring systems, and derived models for massive transfusion, presented their properties, and identified those with potential utility in the prehospital setting. By further validating applicable scoring tools in the prehospital setting, we may begin to administer more timely transfusions in the trauma population.
PICO Summary
Population
Trauma patients (72 studies).
Intervention
Scoping review to characterize the existing literature regarding predictor scores for transfusion in injured patients, to analyse the utility of predictor scores for massive transfusions in the prehospital setting, and to identify pre-hospital predictor scores for future research.
Comparison
Outcome
Sixteen single variables and fifty-two scoring systems were identified for predicting transfusion. Amongst single predictor variables, fluids administered and systolic blood pressure had the highest reported sensitivity (100%) and specificity (89%) for massive transfusion protocol (MTP) activation respectively. Amongst scoring systems for transfusion, the Shock Index and Modified Shock Index had the highest reported sensitivity (96%), while the Pre-arrival Model had the highest reported specificity (95%) for MTP activation. Overall, 20 scores were identified as being applicable to the pre-hospital setting, 25 scores were identified as being potentially applicable, and seven scores were identified as being not applicable.
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Comparison of Risk Scores for Lower Gastrointestinal Bleeding: A Systematic Review and Meta-analysis
Almaghrabi M, Gandhi M, Guizzetti L, Iansavichene A, Yan B, Wilson A, Oakland K, Jairath V, Sey M
JAMA network open. 2022;5(5):e2214253
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Free full text
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Full text
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Editor's Choice
Abstract
IMPORTANCE Clinical prediction models, or risk scores, can be used to risk stratify patients with lower gastrointestinal bleeding (LGIB), although the most discriminative score is unknown. OBJECTIVE To identify all LGIB risk scores available and compare their prognostic performance. DATA SOURCES A systematic search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1990, through August 31, 2021, was conducted. Non-English-language articles were excluded. STUDY SELECTION Observational and interventional studies deriving or validating an LGIB risk score for the prediction of a clinical outcome were included. Studies including patients younger than 16 years or limited to a specific patient population or a specific cause of bleeding were excluded. Two investigators independently screened the studies, and disagreements were resolved by consensus. DATA EXTRACTION AND SYNTHESIS Data were abstracted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline independently by 2 investigators and pooled using random-effects models. MAIN OUTCOMES AND MEASURES Summary diagnostic performance measures (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) determined a priori were calculated for each risk score and outcome combination. RESULTS A total of 3268 citations were identified, of which 9 studies encompassing 12 independent cohorts and 4 risk scores (Oakland, Strate, NOBLADS [nonsteroidal anti-inflammatory drug use, no diarrhea, no abdominal tenderness, blood pressure ≤100 mm Hg, antiplatelet drug use (nonaspirin), albumin <3.0 g/dL, disease score ≥2 (according to the Charlson Comorbidity Index), and syncope], and BLEED [ongoing bleeding, low systolic blood pressure, elevated prothrombin time, erratic mental status, and unstable comorbid disease]) were included in the meta-analysis. For the prediction of safe discharge, the AUROC for the Oakland score was 0.86 (95% CI, 0.82-0.88). For major bleeding, the AUROC was 0.93 (95% CI, 0.90-0.95) for the Oakland score, 0.73 (95% CI, 0.69-0.77) for the Strate score, 0.58 (95% CI, 0.53-0.62) for the NOBLADS score, and 0.65 (95% CI, 0.61-0.69) for the BLEED score. For transfusion, the AUROC was 0.99 (95% CI, 0.98-1.00) for the Oakland score and 0.88 (95% CI, 0.85-0.90) for the NOBLADS score. For hemostasis, the AUROC was 0.36 (95% CI, 0.32-0.40) for the Oakland score, 0.82 (95% CI, 0.79-0.85) for the Strate score, and 0.24 (95% CI, 0.20-0.28) for the NOBLADS score. CONCLUSIONS AND RELEVANCE The Oakland score was the most discriminative LGIB risk score for predicting safe discharge, major bleeding, and need for transfusion, whereas the Strate score was best for predicting need for hemostasis. This study suggests that these scores can be used to predict outcomes from LGIB and guide clinical care accordingly.
PICO Summary
Population
Patients with lower gastrointestinal bleeding (LGIB), (9 studies).
Intervention
Systematic review and meta-analysis to identify all LGIB risk scores available and to compare their prognostic performance.
Comparison
Outcome
Four risk scores were identified: Oakland, Strate, NOBLADS, and BLEED. Summary diagnostic performance measures (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) determined a priori were calculated for each risk score and outcome combination. For the prediction of safe discharge, the AUROC for the Oakland score was 0.86. For major bleeding, the AUROC was 0.93 for the Oakland score, 0.73 for the Strate score, 0.58 for the NOBLADS score, and 0.65 for the BLEED score. For transfusion, the AUROC was 0.99 for the Oakland score and 0.88 for the NOBLADS score. For haemostasis, the AUROC was 0.36 for the Oakland score, 0.82 for the Strate score, and 0.24 for the NOBLADS score.
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Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting
Drop J, Van Den Helm S, Monagle P, Wildschut E, de Hoog M, Gunput STG, Newall F, Dalton HJ, MacLaren G, Ignjatovic V, et al
Research and practice in thrombosis and haemostasis. 2022;6(2):e12687
Abstract
OBJECTIVES Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies. DATA SOURCES Embase, Medline, Web of Science, Cochrane Library and Google Scholar. STUDY SELECTION English original studies of pediatric ECMO patients describing hemostatic tests or outcome. DATA EXTRACTION Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized. DATA SYNTHESIS A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. CONCLUSIONS This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.
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Hypocalcemia as a predictor of mortality and transfusion. A scoping review of hypocalcemia in trauma and hemostatic resuscitation
Kronstedt S, Roberts N, Ditzel R, Elder J, Steen A, Thompson K, Anderson J, Siegler J
Transfusion. 2022
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Free full text
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Abstract
BACKGROUND Calcium plays an essential role in physiologic processes, including trauma's "Lethal Diamond." Thus, inadequate serum calcium in trauma patients exacerbates the effects of hemorrhagic shock secondary to traumatic injury and subsequently poorer outcomes compared to those with adequate calcium levels. Evidence to date supports the consideration of calcium derangements when assessing the risk of mortality and the need for blood product transfusion in trauma patients. This review aims to further elucidate the predictive strength of this association for future treatment guidelines and clinical trials. METHODS Publications were collected on the relationship between i-Ca and the outcomes of traumatic injuries from PubMed, Web of Science, and CINAHL. Manuscripts were reviewed to select for English language studies. Hypocalcemia was defined as i-Ca <1.2 mmol/L. RESULTS Using PRISMA guidelines, we reviewed 300 studies, 7 of which met our inclusion criteria. Five papers showed an association between hypocalcemia and mortality. CONCLUSIONS In adult trauma patients, there has been an association seen between hypocalcemia, mortality, and the need for increased blood product transfusions. It is possible we are now seeing an association between low calcium levels prior to blood product administration and an increased risk for mortality and need for transfusion. Hypocalcemia may serve as a biomarker to show these needs. Therefore, hypocalcemia could potentially be used as an independent predictor for multiple transfusions such that ionized calcium measurements could be used predictively, allowing faster administration of blood products.
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Recommendations for Improving Stop the Bleed: A Systematic Review
Nichols R, Horstman J
Military medicine. 2022
Abstract
INTRODUCTION In response to mass casualty events, The Hartford Consensus brought together subject matter experts across multiple disciplines in health care and public safety to create guidelines and publications intended to improve survivability in active shooter events. Among the recommendations was the earlier recognition and treatment application of life-threatening hemorrhage control. These recommendations culminated in efforts to create the Stop the Bleed Campaign, which aims to empower the layperson to render aid in a life-threatening bleeding emergency. As of February 2020, the program has held over 86,000 courses, trained over 1.4 million attendees, and over 77,000 instructors since its inception. In addition to spreading within the United States, American College of Surgeons (ACS) Stop the Bleed (StB) classes have been held in 118 different countries. This systematic narrative review aims to answer the following research question: What does the ACS StB Initiative do well, and where can it improve? MATERIALS AND METHODS The following search terms were utilized: "Stop the Bleed," "American College of Surgeons," "bleeding control," "first-aid," tourniquet, "wound pack," "direct pressure" hemorrhage, and bystander. The inclusion criteria were that the article needed to speak to the program or some aspect of bystander first aid, the article needed to be in a civilian setting, the article needed to be more than a case study or overview, and the first aid tools needed to be in the StB curriculum. 4 databases were searched, which produced 138 articles for screening. One hundred four full-text articles were able to be retrieved, and 56 articles were determined to meet the inclusion criteria once the full text was reviewed. RESULTS Fifty-six articles were included in the final review and were placed into the following categories: Needs Within the Community, Confidence and Knowledge, Training Modalities, Barriers and Gaps in Training, Instructor Selection, Skill Retention, and Patient Outcomes. The articles were then organized into each outcome for synthesis and reporting of the results. The program overwhelmingly improves short-term confidence, but gaps in skill retention, data collection on patient outcomes, and settings that would benefit were identified. CONCLUSION StB is an effective tool in building confidence in laypersons, which is its biggest strength. A review of the literature shows several areas where the curriculum and materials could be better developed. Research can also be further refined to better quantify the program's impact.
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Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review
Zhu, Z., Yu, Y., Hong, K., Luo, M., Ke, Y.
World Journal of Emergency Surgery : Wjes. 2022;17(1):48
Abstract
OBJECTIVE Viscoelastic hemostatic assay (VHA) provides a graphical representation of a clot's lifespan and reflects the real time of coagulation. It has been used to guide trauma resuscitation; however, evidence of the effectiveness of VHAs is still limited. This systematic review aims to summarize the published evidence to evaluate the VHA-guided strategy in resuscitating trauma patients. METHODS The PubMed, Embase, and Web of Science databases were searched from their inception to December 13, 2021. Randomized controlled trials (RCTs) or observational studies comparing VHA-guided transfusion to controls in resuscitating trauma patients were included in this systematic review. RESULTS Of the 7743 records screened, ten studies, including two RCTs and eight observational studies, met the inclusion criteria. There was great heterogeneity concerning study design, enrollment criterion, VHA device, VHA-guided strategy, and control strategy. Thrombelastography (TEG) was used as a guiding tool for transfusion in eight studies, and rotational thromboelastometry (ROTEM), and TEG or ROTEM were used in the other two studies. The overall risk of bias assessment was severe or mild in RCTs and was severe or moderate in observational studies. The main outcomes reported from the included studies were blood transfusion (n = 10), mortality (n = 10), hospital length of stay (LOS) (n = 7), intensive care unit LOS (n = 7), and cost (n = 4). The effect of the VHA-guided strategy was not always superior to the control. Most of the studies did not find significant differences in the transfusion amount of red blood cells (n = 7), plasma (n = 5), platelet (n = 7), cryoprecipitate/fibrinogen (n = 7), and mortality (n = 8) between the VHA-guided group and control group. Notable, two RCTs showed that the VHA-guided strategy was superior or equal to the conventional coagulation test-guided strategy in reducing mortality, respectively. CONCLUSION Although some studies demonstrated VHA-guided strategy probable benefit in reducing the need for blood transfusion and mortality when resuscitating trauma patients, the evidence is still not robust. The quality of evidence was primarily downgraded by the limited number of included studies and great heterogeneity and severe risk of bias in these. Further studies are strongly recommended.
