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Reporting Bias is Highly Prevalent in Systematic Reviews and Meta-Analyses of Platelet Rich Plasma Injections for Hip Osteoarthritis
Kim, D., Bashrum, B. S., Kotlier, J. L., Mayfield, C. K., Thompson, A. A., Abu-Zahra, M., Hwang, M., Bolia, I. K., Petrigliano, F. A., Liu, J. N.
Arthroscopy, sports medicine, and rehabilitation. 2024;6(1):100851
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Editor's Choice
Abstract
PURPOSE To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. METHODS The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. RESULTS Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. CONCLUSIONS Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. CLINICAL RELEVANCE It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.
PICO Summary
Population
Patients with hip osteoarthritis (15 systematic reviews).
Intervention
Systematic review to describe the incidence and types of spin bias in systematic reviews of platelet-rich plasma injections for hip osteoarthritis and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.
Comparison
Outcome
All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration.
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Role of hydroxyurea therapy in the prevention of organ damage in sickle cell disease: a systematic review and meta-analysis
Khargekar, N., Banerjee, A., Athalye, S., Mahajan, N., Kargutkar, N., Tapase, P., Madkaikar, M.
Systematic reviews. 2024;13(1):60
Abstract
BACKGROUND Hydroxyurea is an affordable drug that reduces vaso-occlusive crises and transfusion requirements in sickle cell disease. However, its effectiveness in preventing chronic organ damage is still unclear. This systematic review and meta-analysis aimed to evaluate the role of hydroxyurea in preventing organ morbidity. METHOD We included original articles published in English from 1st January 1990 to 31st January 2023, reporting hydroxyurea therapy and organ damage from PubMed, Google Scholar, Scopus, and CrossRef databases. A total of 45 studies with 4681 sickle cell disease patients were evaluated for organ damage. RESULTS Our analysis showed that hydroxyurea intervention significantly lowered transcranial Doppler and tricuspid regurgitant velocity, with a standardized mean difference of - 1.03 (- 1.49; - 0.58); I (2) = 96% and - 1.37 (CI - 2.31, - 0.42); I (2) = 94%, respectively. Moreover, the pooled estimate for albuminuria showed a beneficial effect post-hydroxyurea therapy by reducing the risk of albuminuria by 58% (risk ratio of 0.42 (0.28; 0.63); I (2) = 28%). CONCLUSION Our study found that a hydroxyurea dose above 20 mg/kg/day with a mean rise in HbF by 18.46% post-hydroxyurea therapy had a beneficial role in reducing transcranial doppler velocity, tricuspid regurgitant velocity, albuminuria, and splenic abnormality. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42023401187.
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Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities
Khalid, S., Ali, A., Deepak, F., Zulfiqar, M. S., Malik, L. U., Fouzan, Z., Nasr, R. A., Qamar, M., Bhattarai, P.
Annals of medicine and surgery (2012). 2024;86(1):361-372
Abstract
INTRODUCTION Knee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options. METHODS PubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. RESULTS Our meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I (2)=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I(2)=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I (2)=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I (2)=68%) compared to CS injections, with the most significant improvement observed at 6 months. CONCLUSIONS PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.
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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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The role of preoperative transfusion in sickle cell disease, a systematic review and meta-analysis
Abdu, Y., Rahhal, A., Ahmed, K., Adli, N., Abdou, M., Ali, E. A. H., Al-Kindi, S., Al Rasheed, M., Altooq, J., Bougmiza, I., et al
Blood reviews. 2024;:101183
Abstract
This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022. Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75-10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.
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Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review
Vogel, J. P., Nguyen, P. Y., Ramson, J., De Silva, M. S., Pham, M. D., Sultana, S., McDonald, S., Adu-Bonsaffoh, K., McDougall, A. R. A.
American journal of obstetrics and gynecology. 2024
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Editor's Choice
Abstract
OBJECTIVE Care bundles are a promising approach to reducing postpartum hemorrhage (PPH)-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for PPH prevention and/or treatment. DATA SOURCES We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to 9 June 2023) and ClinicalTrials.gov and ICTRP (last 5 years) using a phased search strategy, combining terms for PPH and care bundles. STUDY ELIGIBILITY CRITERIA Peer-review studies evaluating PPH-related care bundles. Care bundles were defined as interventions comprising three or more components implemented collectively, concurrently or in rapid succession. Randomized and non-randomized controlled trials, interrupted time series and before-after studies (controlled or uncontrolled) were eligible. STUDY APPRAISAL AND SYNTHESIS Risk of bias assessed using ROB2 (randomized trials) and ROBINS-I (non-randomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies we used effect direction tables and summarized results narratively. RESULTS Twenty-two studies were included for analysis. For prevention-only bundles (two studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization and ICU stay, and maternal wellbeing. For treatment-only bundles (nine studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (RR 0.40; 95% CI 0.32-0.50) as well as blood transfusion for bleeding, PPH, severe PPH, and mean blood loss. One non-randomized trial and seven uncontrolled studies suggest other PPH treatment bundles might reduce blood loss and severe PPH, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative (CMQCC) care bundle may reduce severe maternal morbidity (RR 0.64, 95% CI 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSIONS The E-MOTIVE intervention improves PPH-related outcomes among women delivering vaginally, and the CMQCC bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.
PICO Summary
Population
Women experiencing vaginal birth or caesarean delivery (22 studies).
Intervention
Care bundles for postpartum haemorrhage (PPH) prevention and/or treatment.
Comparison
Outcome
For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization and intensive care unit stay, and maternal wellbeing. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (RR 0.40; 95% CI [0.32, 0.50] as well as blood transfusion for bleeding, PPH, severe PPH, and mean blood loss. One non-randomized trial and seven uncontrolled studies suggest other PPH treatment bundles might reduce blood loss and severe PPH, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative (CMQCC) care bundle may reduce severe maternal morbidity (RR 0.64; 95% CI [0.57, 0.72]. Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types.
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[Translated article] Efficacy of platelet-rich plasma in rotator cuff repair: systematic review and meta-analysis
Sánchez-Losilla, C., Ferré-Aniorte, A., Álvarez-Díaz, P., Barastegui-Fernández, D., Cugat, R., Alentorn-Geli, E.
Revista espanola de cirugia ortopedica y traumatologia. 2024
Abstract
OBJECTIVE To analyze the efficacy and safety after the application of platelet-rich-plasma (PRP) as an adjuvant in arthroscopic rotator cuff repairs. MATERIAL AND METHODS A bibliographic search of the literature of prospective studies with level of evidence one or two was carried out from January 2004 to December 2021, including studies that compare the functional and re-tear results after arthroscopic cuff repair rotator with or without PRP. RESULTS A total of 281 articles were identified, of which 14 met the inclusion criteria. The overall re-rupture rate was 24%. In the PRP group, a decrease in the re-rupture rate and better functional results were demonstrated, although these differences were not significant. CONCLUSIONS Adjuvant treatment with PRP has shown promising results, although there is not yet enough evidence to provide a clear advantage for routine use in clinical practice.
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Effectiveness of Injectable Platelet-Rich Fibrin in the Treatment of Oral Lichen Planus: A Systematic Review and Meta-Analysis
Gupta, N., Bhargava, A., Saigal, S., Sharma, S., Patel, M., Prakash, O.
Cureus. 2024;16(1):e51626
Abstract
Oral lichen planus (OLP) is a chronic inflammatory condition affecting the oral mucosa. The current review investigated the potential effectiveness of injectable platelet-rich fibrin (i-PRF) as a treatment for OLP when compared to other interventions. The current review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy was implemented across databases such as PubMed, Embase, Scopus, Web of Science, CINAHL, and Google Scholar. The search utilized a combination of Boolean operators (AND, OR) and Medical Subject Headings (MeSH) terms to capture relevant studies. Comparative clinical studies focusing on i-PRF as a treatment for OLP and other interventions were included. Outcomes assessed were pain, surface area of lesions, and patient satisfaction. Review Manager 5.4 was used for statistical analysis. The Risk of Bias 2.0 (RoB 2.0) tool was used to assess the methodological quality of the studies. Three studies were included for the final analysis. The findings indicated that both the i-PRF and comparison treatment groups demonstrated reductions in pain and lesion size. The post-treatment Visual Analogue Scale (VAS) scores showed a decrease in pain intensity, and there was an improvement in lesion extension in the i-PRF-treated sites. The results also revealed increased patient satisfaction with i-PRF treatment. Adverse effects were not reported or specified in the included studies. Quantitative analysis for pain (VAS) showed a mean difference of 0.38 (95% CI: 0.63-1.40), but there was no significant difference between the i-PRF and control groups at p=0.46. Though intragroup differences showed statistically significant differences between pre and post intervention, intergroup differences were not significant for any of the assessed outcomes. The findings from this study suggest that i-PRF holds promise as a potential treatment for OLP. The use of i-PRF resulted in pain reduction, lesion size improvement, and increased patient satisfaction. However, it is important to consider the limitations of the included studies, such as variability in study designs, small sample sizes, and the limited number of studies.
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Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta-analysis
Gibbs, V. N., Champaneria, R., Sandercock, J., Welton, N. J., Geneen, L. J., Brunskill, S. J., Dorée, C., Kimber, C., Palmer, A. J., Estcourt, L. J.
The Cochrane database of systematic reviews. 2024;1(1):Cd013295
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Editor's Choice
Abstract
BACKGROUND Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care. OBJECTIVES To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology. SEARCH METHODS We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants. DATA COLLECTION AND ANALYSIS We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received. MAIN RESULTS We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials). AUTHORS' CONCLUSIONS We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.
PICO Summary
Population
People undergoing elective hip or knee surgery (102 randomised controlled trials).
Intervention
Antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.
Comparison
Placebo or one of the active interventions.
Outcome
The primary outcomes were the proportion of participants requiring an allogeneic blood transfusion and all‐cause mortality. Tranexamic acid was the most common drug studied. Mortality was not reported by many trials. Tranexamic acid interventions consistently ranked higher than other treatments such as aprotinin, EACA and topical fibrin sealants compared with placebo. The authors noted that mixed routes of administration (oral and intra‐articular, intravenous and intra‐articular) appear to be more effective than single routes of administration and higher doses of tranexamic acid feature higher up the treatment ranking hierarchy. The authors identified 30 ongoing studies.