Abstract

BACKGROUND We assessed quality of life (QoL) of patients undergoing surgery for proximal femur fracture and performed a cost-effectiveness analysis of haemostatic drugs for reducing postoperative bleeding. METHODS We analysed data from an open, multicentre, parallel, randomized controlled clinical trial (RCT) that assessed the efficacy and safety of tranexamic acid (TXA group) and fibrin glue (FG group) administered topically prior to surgical closure, compared with usual haemostasis methods (control group). For this study we conducted a cost-effectiveness analysis of these interventions from the Spanish Health System perspective, using a time horizon of 12 months. The cost was reported in $US purchasing power parity (USPPP). We calculated the incremental cost-effectiveness ratio (ICER) per QALY (quality-adjusted life-year). RESULTS We included 134 consecutive patients from February 2013 to March 2015: 42 patients in the TXA group, 46 in the FG group, and 46 in the control group. Before the fracture, EuroQol visual analogue scale (EQ-VAS) health questionnaire score was 68.6. During the 12 months post-surgery, the intragroup EQ-VAS improved, but without reaching pre-fracture values. There were no differences between groups for EQ-VAS and EuroQol 5 dimensions 5 levels (EQ-5D-5L) health questionnaire score, nor in hospital stay costs or medical complication costs. Nevertheless, the cost of one FG treatment was significantly higher (399.1 $USPPP) than the cost of TXA (12.9 $USPPP) or usual haemostasis (0 $USPPP). When comparing the cost-effectiveness of the interventions, FG was ruled out by simple dominance since it was more costly (13,314.7 $USPPP) than TXA (13,295.2 $USPPP) and less effective (utilities of 0.0532 vs. 0.0734, respectively). TXA compared to usual haemostasis had an ICER of 15,289.6 $USPPP per QALY). CONCLUSIONS There were no significant differences between the intervention groups in terms of postoperative changes in QoL. However, topical TXA was more cost-effective than FG or usual haemostasis. TRIAL REGISTRATION ClinicalTrials.gov: NCT02150720. Date of registration 30/05/2014. Retrospectively registered.

Abstract

BACKGROUND The frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. This is an update of a previously published Cochrane Review. OBJECTIVES To assess the clinical effectiveness and harms of interventions for treating leg ulcers in people with sickle cell disease. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017. SELECTION CRITERIA Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. We used GRADE to assess the quality of the evidence. MAIN RESULTS Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms. AUTHORS' CONCLUSIONS Given the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.

Abstract

Background: Leukocytes contained in the allogeneic packed red blood cell (PRBC) are the cause of certain adverse reactions associated with blood transfusion. Leukoreduction consists of eliminating leukocytes in all blood products below the established safety levels for any patient type. In this systematic review, we appraise the clinical effectiveness of allogeneic leukodepleted (LD) PRBC transfusion for preventing infections and death in patients undergoing major cardiovascular surgical procedures. Methods: We searched randomized controlled trials (RCT), enrolling patients undergoing a major cardiovascular surgical procedure and transfused with LD-PRBC. Data were extracted, and risk of bias was assessed according to Cochrane guidelines. In addition, trial sequential analysis (TSA) was used to assess the need of conducting additional trials. Quality of the evidence was assessed using the GRADE approach. Results: Seven studies met the eligibility criteria. Quality of the evidence was rated as moderate for both outcomes. The risk ratio for death from any cause comparing the LD-PRBC versus non-LD-PRBC group was 0.69 (CI 95% = 0.53 to 0.90; I (2) = 0%). The risk ratio for infection in the same comparison groups was 0.77 (CI 95% = 0.66 to 0.91; I (2) = 0%). TSA showed a conclusive result in this outcome. Conclusions: We found evidence that supports the routine use of leukodepletion in patients undergoing a major cardiovascular surgical procedure requiring PRBC transfusion to prevent death and infection. In the case of infection, the evidence should be considered sufficient and conclusive and hence indicated that further trials would not be required.

Abstract

BACKGROUND Red blood cell (RBC) transfusions are essential in health care. The quality of recommendations included in clinical practice guidelines (CPG), regarding this intervention, has not been systematically evaluated. This paper systematically assessed CPGs for RBC-transfusion, to appraise their methodological quality, to explore changes in quality over time, and to assess the consistency of the hemoglobin threshold (HT) recommendations. METHODS We searched for CPGs that included recommendations of RBC-transfusion in generic databases, compiler entities, registries, clearinghouses and guideline developers. Three reviewers extracted data on CPGs characteristics and HT recommendations, independently appraised the quality of the studies using AGREE II and resolved disagreements by consensus. RESULTS We examined 16 CPGs. Mean scores (mean +/- SD) were: scope and purpose (59.4% +/- 19.8%), stakeholder involvement (43.2% +/- 22.6%), rigor of development (50% +/- 25%), clarity of presentation (74.4% +/- 12.6%), applicability (19.4% +/- 18.8%), and editorial independence (41% +/- 30%). Seven CPGs recommended a restrictive strategy for RBC transfusion; four CPGs gave a guarded statement considering an HT of 7 g/dL, as safe to prescribe an RBC transfusion. Eight CPGs did not provide an HT stating that RBC transfusions should not be prescribed by HT alone. CONCLUSIONS Only 3 out of the 16 evaluated CPGs were "recommended" by the independent evaluators. Four domains "stakeholder involvement," "rigor of development," applicability," and "editorial independence" had serious shortcomings. Recommendations about the use of an HT for RBC-transfusion were heterogeneous among guidelines. Greater efforts are needed to provide high-quality CPGs in the RBC-transfusion practice.

Abstract

INTRODUCTION We assessed the efficacy of fibrin sealant (FS) and tranexamic acid (TXA) administered topically in patients with a hip fracture treated with prosthetic replacement. MATERIALS AND METHODS Parallel, multicentre, open label, randomised, clinical trial. We compared three interventions to reduce blood loss: (1) 10 ml of FS, (2) 1 g of topical TXA, both administered at the end of the surgery, and (3) usual haemostasis (control group). The main outcome was blood loss collected in drains. Other secondary variables were total blood loss, hidden blood loss, transfusion rate, average hospital stay, complications, adverse events, and mortality. RESULTS A total of 158 patients were included, 56 in the FS group, 52 in the TXA group, and 50 in the control group. The total amount of blood collected in drains was lower in the TXA group (148.6 ml, SD 122.7 in TXA; 168.2 ml, SD 137.4 in FS; and 201.5 ml, SD 166.5 in control group) without achieving statistical significance (p = 0.178). The transfusion rate was lower in the TXA group (32.7%), compared with FS group (42.9%) and control group (44.0%), without statistical significance (p = 0.341). There were no complications or adverse effects related to the evaluated interventions. CONCLUSIONS The use of TXA and FS administered topically prior to surgical closure in patients with a sub-capital femoral fracture undergoing arthroplasty did not significantly reduce either postoperative blood loss or transfusion rate, compared with a group that only received usual haemostasis.

Abstract

BACKGROUND Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors with the potential to improve the healing of chronic wounds. This is the first update of a review first published in 2012. OBJECTIVES To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS In June 2015, for this first update, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library): Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched for ongoing and unpublished clinical trials in the WHO International Clinical Trials Registry Platform (ICTRP) (searched January 2015). We did not impose any restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. We did not apply any date or language restrictions. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology, including two reviewers independently selecting studies for inclusion, extracting data, and assessing risk of bias. MAIN RESULTS The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks).It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I2 = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I2 = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I2 = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I2 = 0%, low quality evidence from 3 trials, 102 participants). AUTHORS' CONCLUSIONS PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.

Abstract

INTRODUCTION Tranexamic acid (TXA) is becoming widely used in orthopedic surgery to reduce blood loss and transfusion requirements, but consensus is lacking regarding the optimal route and dose of administration. The aim of this study was to compare the efficacy and safety of topical and intravenous routes of TXA with routine hemostasis in patients undergoing primary total knee arthroplasty (TKA). MATERIALS AND METHODS We performed a randomized, multicenter, parallel, open-label clinical trial in adult patients undergoing primary TKA. Patients were divided into three groups of 50 patients each: Group 1 received 1 g topical TXA, Group 2 received 2 g intravenous TXA, and Group 3 (control group) had routine hemostasis. The primary outcome was total blood loss. Secondary outcomes were hidden blood loss, blood collected in drains, transfusion rate, number of blood units transfused, adverse events, and mortality. RESULTS One hundred and fifty patients were included. Total blood loss was 1021.57 (481.09) mL in Group 1, 817.54 (324.82) mL in Group 2 and 1415.72 (595.11) mL in Group 3 (control group). Differences in total blood loss between the TXA groups and the control group were clinically and statistically significant (p < 0.001). In an exploratory analysis differences between the two TXA groups were not statistically significant (p = 0.073) Seventeen patients were transfused. Transfusion requirements were significantly higher in Group 3 (p = 0.005). No significant differences were found between groups regarding adverse events. CONCLUSION We found that 1 g of topical TXA and 2 g of intravenous TXA were both safe strategies and more effective than routine hemostasis to reduce blood loss and transfusion requirements after primary TKA. LEVEL OF EVIDENCE I.

Abstract

BACKGROUND The goals of the treatment of muscle injuries are to shorten the time of healing and to avoid relapses. The aim of this study was to assess the efficacy of autologous platelet-rich plasma (PRP) in the healing of muscle injuries. MATERIALS AND METHODS A multicentre, randomised, double-blind, parallel, controlled clinical trial was conducted in 71 patients (81.8% males) aged 45.6 (SD=10.0) years with muscle tears in the legs and haematoma. The haematoma was evacuated in all patients. Thirty-three patients were randomised to a single dose of autologous PRP and 38 patients to simulation of PRP administration. The primary end-point was time to complete recovery of muscle injury. Secondary end-points were pain, relapses, ultrasound parameters, and adverse events. The total follow-up per patient was 12 months. RESULTS Time to complete recovery after the treatment was 31.63 days (SD=15.38) in the PRP group, and 38.43 days (SD=18.58) in the control group (p=0.261). Pain decreased over time in both groups without statistical differences between them. Eight patients relapsed (seven in the control group, and one in the PRP group). There were no adverse effects related to the interventions. DISCUSSION Autologous PRP did not significantly improve the time to healing compared to that in the control group.

Abstract

BACKGROUND Postoperative blood loss in patients after total knee arthroplasty may cause local and systemic complications and influence clinical outcome. The aim of this study was to assess whether fibrin glue or tranexamic acid reduced blood loss compared with routine hemostasis in patients undergoing total knee arthroplasty. METHODS A randomized, single-center, parallel, open clinical trial was performed in adult patients undergoing primary total knee arthroplasty. Patients were divided into four groups. Group 1 received fibrin glue manufactured by the Blood and Tissue Bank of Catalonia, Group 2 received Tissucol (fibrinogen and thrombin), Group 3 received intravenous tranexamic acid, and Group 4 (control) had no treatment other than routine hemostasis. The primary outcome was total blood loss collected in drains after surgery. Secondary outcomes were the calculated hidden blood loss, transfusion rate, preoperative and postoperative hemoglobin, number of blood units transfused, adverse events, and mortality. RESULTS One hundred and seventy-two patients were included. The mean total blood loss (and standard deviation) collected in drains was 553.9 +/- 321.5 mL for Group 1, 567.8 +/- 299.3 mL for Group 2, 244.1 +/- 223.4 mL for Group 3, and 563.5 +/- 269.7 mL for Group 4. In comparison with the control group, Group 3 had significantly lower total blood loss (p < 0.001), but it was not significantly lower in Groups 1 and 2. The overall rate of patients who had a blood transfusion was 21.1% (thirty-five of 166 patients analyzed per protocol). Two patients required transfusion in Group 3 compared with twelve patients in Group 4 (p = 0.015). No significant difference was observed between the two fibrin glue groups and the control group with regard to the need for transfusion. There was no difference between groups with regard to the percentage of adverse events. CONCLUSIONS Neither type of fibrin glue was more effective than routine hemostasis in reducing postoperative bleeding and transfusion requirements, and we no longer use them. However, this trial supports findings from previous studies showing that intravenous tranexamic acid can decrease postoperative blood loss. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Abstract

BACKGROUND Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors and has the potential to aid wound healing. OBJECTIVES To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS We searched the Cochrane Wounds Group Specialised Register (searched 15 August 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8); Ovid MEDLINE (1950 to August Week 1 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, August 14, 2012); Ovid EMBASE (1980 to 2012 Week 32); EBSCO CINAHL (1982 to 10 August 2012) and International Clinical Trials Registry Platform (ICTRP)(accessed 22 August 2012). No date or language restrictions were applied. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. DATA COLLECTION AND ANALYSIS Two review authors independently assessed each study against the inclusion criteria, extracted data and assessed risk of bias for all included trials. We calculated the risk ratio (RR) or the mean difference (MD) and time to wound healing was analysed as survival data using the hazard ratio (HR). We considered heterogeneity as significant when I(2) was >75%. MAIN RESULTS Nine eligible RCTs were included, with a total of 325 participants of whom 44% were women. The median number of participants per RCT was 26 (range 10 to 86). Four RCTs recruited people with mixed chronic wounds (there were participants with wounds caused by more than one aetiology and participants who had wounds of several aetiologies in the same trial), three RCTs recruited people with venous leg ulcers and two RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range eight to 40 weeks).One study was at low risk of bias, three studies were at high risk of bias with the remainder being at overall unclear risk of bias. The proportion of completely healed chronic wounds was reported in seven RCTs that compared PRP with standard treatment or placebo, with no statistically significant difference between the groups, in diabetic foot ulcers (RR 1.16; 95% CI 0.57 to 2.35), in venous leg ulcers (pooled RR 1.02; 95% CI 0.81 to 1.27; I(2)=0% ) and in mixed chronic wounds (pooled RR 1.85; 95% CI 0.76 to 4.51; I(2)=42%). The total area epithelialised at the end of the intervention was reported in three RCTs of mixed chronic wounds, there was no statistically significant difference between the groups (pooled MD -1.94 cm(2); 95% CI -4.74 to 0.86; I(2)=47%). The percentage of wound area healed was reported in two RCTs of mixed chronic wounds, and results were statistically significant in favour of the PRP group (RR 51.78%; 95% CI 32.70 to 70.86; I(2)= 0%). Wound complications like infection or necrosis were reported by three RCTs, and there was no statistically significant difference between groups (RR 1.08; 95% CI 0.31 to 3.73). Adverse effects were reported by three studies and there was no statistically significant difference between people treated with PRP and those not given PRP (pooled RR 1.07; 95% CI 0.32 to 3.58; I(2)=0%). AUTHORS' CONCLUSIONS There is currently no evidence to suggest that autologous PRP is of value for treating chronic wounds. However, current evidence is based on a small number of RCTs, most of which are either at high or unclear risk of bias. Well-designed and adequately powered clinical trials are needed.