Quality of life and cost-effectiveness analysis of topical tranexamic acid and fibrin glue in femur fracture surgery.

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.

Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial.

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.

Ácido tranexámico en cirugía ortopédica / Tranexamic acid in orthopedic surgery

El sangrado perioperatorio en ocasiones conduce a transfusiones sanguíneas no exentas de complicaciones y riesgos, con un alto gasto sanitario. Entre otros métodos de prevención, el tratamiento con ácido tranexámico (TXA) ha mostrado ser efectivo en la disminución de las pérdidas sanguíneas quirúrgicas y especialmente en el postoperatorio inmediato. Al respecto, los estudios que lo han evaluado en cirugía ortopédica muestran su eficacia y seguridad, administrado por vía tanto intravenosa como intraarticular. Las dosis habituales por vía intravenosa evaluadas oscilan entre 10 y 20 mg/kg, o en dosis fijas de 1 a 2 g, mientras por vía intraarticular varía entre 250 mg y 3 g. El TXA como antifibrinolítico tiene un potencial efecto trombótico y está contraindicado en aquellos pacientes con riesgo o antecedentes de trombosis. Su administración por vía tópica podría ser más segura aunque se precisan estudios que lo confirmen (AU)

Perioperative bleeding may require blood transfusions, which are sometimes not without complications and risks, with the subsequent increase in health care costs. Among other prevention methods, treatment with tranexamic acid (ATX) has shown to be effective in reducing surgical blood loss, especially in the immediate postoperative period. In this regard, studies evaluating ATX in orthopedic surgery show that it is effective and safe when administered intravenously or intra-articularly. The usual evaluated intravenous doses range between 10 mg/Kg and 20 mg/kg or a fixed dose of 1 g to 2 g; while intra-articularly, it varies between 250 mg and 3 g. ATX, as an anti-fibrinolytic has a potential thrombotic effect, thus it is contraindicated in those patients at risk or with a history of thrombosis. Its topical administration may be safer, but studies are needed to confirm this (AU)

[Tranexamic acid in orthopedic surgery]. / Ácido tranexámico en cirugía ortopédica.

Perioperative bleeding may require blood transfusions, which are sometimes not without complications and risks, with the subsequent increase in health care costs. Among other prevention methods, treatment with tranexamic acid (ATX) has shown to be effective in reducing surgical blood loss, especially in the immediate postoperative period. In this regard, studies evaluating ATX in orthopedic surgery show that it is effective and safe when administered intravenously or intra-articularly. The usual evaluated intravenous doses range between 10mg/Kg and 20mg/kg or a fixed dose of 1g to 2g; while intra-articularly, it varies between 250 mg and 3g. ATX, as an anti-fibrinolytic has a potential thrombotic effect, thus it is contraindicated in those patients at risk or with a history of thrombosis. Its topical administration may be safer, but studies are needed to confirm this.

Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial.

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.

A randomized, double-blind multicentre clinical trial comparing the efficacy of calcium dobesilate with placebo in the treatment of chronic venous disease.

OBJECTIVE: To assess the efficacy of calcium dobesilate on the quality-of-life (QoL) of patients with chronic venous disease (CVD). DESIGN: Randomised, parallel, double blind, placebo-controlled clinical trial. METHODS: Patients were recruited from vascular surgery clinics and randomised to 500mg capsules of calcium dobesilate twice a day for 3 months or placebo. The primary outcome measure was 'QoL after 3 months' treatment measured by the specific Chronic Insufficiency Venous International Questionnaire (CIVIQ). Secondary outcomes were QoL at 12 months and assessment of the CVD signs and symptoms. The principal analysis was undertaken on the intention-to-treat (ITT) data. RESULTS: Five hundred and nine patients were recruited (246 to calcium dobesilate and 263 to placebo). The analysis of the 'QoL after 3 months' showed no significant differences between groups (p=0.07). For secondary outcomes, oedema and symptoms of CVD, there were no significant differences between groups. In a multi-factorial analysis, the 'QoL at 12 months' was better in the calcium dobesilate group than in placebo group (p=0.02). CONCLUSIONS: Treatment with calcium dobesilate was not found to be superior to placebo on the QoL of CVD patients. The sustained effect of calcium dobesilate observed after treatment should be confirmed in future studies.

Calcitonin for metastatic bone pain.

BACKGROUND: Pain is the most frequent symptom experienced by cancer patients, its intensity dependent on the site of the tumour. Tumours that compromise bone or nervous structures due to the bone destruction process are the most painful. There are several treatments to deal with pain (and other symptoms) caused by bone metastases. The hormone, calcitonin, has the potential to relieve pain, and also retain bone density, thus reducing the risk of fractures. This review is an update of a previously published review in The Cochrane Library (Issue 3, 2003) on this topic. OBJECTIVES: To assess the effectiveness of calcitonin in controlling metastatic bone pain and reducing bone complications (hypercalcemia, fractures and nerve compression) in patients with bone metastases. SEARCH STRATEGY: Electronic searches were performed in MEDLINE (1966 to 2005), EMBASE (1974 to 2005), the Cochrane Central Register of Controlled Trials (Issue 2, 2005), specialised registers of the Cochrane Cancer Network and of the Cochrane Pain, Palliative and Supportive Care Group. Registers of clinical trials in progress were also searched. SELECTION CRITERIA: Studies were included if they were randomised, double-blind clinical trials of patients with metastatic bone pain, treated with calcitonin, where the major outcome measure was pain, assessed at four weeks or longer. DATA COLLECTION AND ANALYSIS: Study selection and data extraction were performed by two independent review authors. Only two studies (90 patients) were eligible for inclusion in the review and therefore meta-analysis of the data was not possible. Intention-to-treat analysis was performed by imputing all missing values as adverse outcomes. MAIN RESULTS: Of the two small studies included in the review, one study showed a non-significant effect of calcitonin in the number of patients with total pain reduction (RR 2.50; CI 95%, 0.55 to 11.41). The second study provided no evidence that calcitonin reduced analgesia consumption (RR 1.05; CI 95%, 0.90 to 1.21) in patients with painful bone metastases. There was no evidence that calcitonin was effective in controlling complications due to bone metastases; for improving quality of life; or patients' survival. Although not statistically significant, a greater number of adverse effects were observed in the groups given calcitonin in the two included studies (RR 3.35, CI 95%, 0.72 to 15.66). AUTHORS' CONCLUSIONS: The limited evidence currently available does not support the use of calcitonin to control pain from bone metastases. Since the last version of this review, none of the new relevant studies have provided additional information on this treatment, in contrast to other therapeutic approaches that should be considered.

Meta-analysis of flavonoids for the treatment of haemorrhoids.

BACKGROUND: The aim of the study was to evaluate the impact of flavonoids on those symptoms important to patients with symptomatic haemorrhoids. METHODS: A comprehensive search strategy was used. All published and unpublished randomized controlled trials comparing any type of flavonoid to placebo or no therapy in patients with symptomatic haemorrhoids were included. Two reviewers independently screened studies for inclusion, retrieved all potentially relevant studies and extracted data. RESULTS: Fourteen eligible trials randomized 1514 patients. Studies were of moderate quality and showed variability in the results with potential publication bias. Meta-analyses using random-effects models suggested that flavonoids decrease the risk of not improving or persisting symptoms by 58 per cent (relative risk (RR) 0.42 (95 per cent confidence interval (c.i.) 0.28 to 0.61)) and showed an apparent reduction in the risk of bleeding (RR 0.33 (95 per cent c.i. 0.19 to 0.57)), persistent pain (RR 0.35 (95 per cent c.i. 0.18 to 0.69)), itching (RR 0.65 (95 per cent c.i. 0.44 to 0.97)) and recurrence (RR 0.53 (95 per cent c.i. 0.41 to 0.69)). CONCLUSION: Limitations in methodological quality, heterogeneity and potential publication bias raise questions about the apparent beneficial effects of flavonoids in the treatment of haemorrhoids.

[Descriptive analysis of chronic pain clinics operating in Spain in 2001]. / Análisis descriptivo en el año 2001 de las Unidades de Tratamiento del Dolor Crónico en España.

OBJECTIVES: To describe the characteristics and care approaches to care of chronic pain clinics operating in Spain in 2001. DESIGN: Cross-sectional mail survey of pain clinics in Spain. SETTING: Chronic pain clinics in Spain. STATISTICAL ANALYSIS: Descriptive statistics of pain clinics responding to the questionnaire. RESULTS: Fifty-six of the 79 pain clinics (70.8%) responded; 57.1% were in public facilities, 55.4% were affiliated with medical schools, and 53.6% were interdisciplinary units. Both acute and chronic pain were treated by 72.4% of the respondents. Anesthesiology departments supervised 89.3% of the clinics. Only 57.1% had staff permanently assigned to the pain clinic. A mean 2194 (SD 2041) visits by patients were received annually. The most commonly applied treatments were drugs, blocks, spinal techniques, and transcutaneous electrical nerve stimulation. Implantable systems were more frequently used in chronic pain clinics than in mixed pain clinics, and in university-affiliated clinics than in non-teaching facilities (P=0.03 in both comparisons). A psychological approach was used more often in interdisciplinary clinics than in units operated by staff from a single specialty (P<0.01). CONCLUSIONS: Chronic pain clinics were not evenly distributed throughout Spain. The number of patients treated at pain clinics was high. The various characteristics of pain clinics--such as funding source, interdisciplinarity, university affiliation, and specialization in chronic pain--a were factors that affected the use of certain treatments.

Análisis descriptivo en el año 2001 de las Unidades de Tratamiento del Dolor Crónico en España / Descriptive analysis of chronic pain clinics operating in Spain in 2001

OBJETIVO: Descripción de las características y actividad asistencial de las Unidades de Dolor Crónico (UDC)de España durante el año 2001.DISEÑO: Estudio transversal basado en una encuesta por correo realizada a las UDC españolas. UNIDAD DE ESTUDIO: UDC españolas. ANÁLISIS: Análisis descriptivo de las UDC que cumplimentaron la encuesta. RESULTADOS: De 79 UDC encuestadas, respondieron56 (70,8%), de las cuales el 57,1% eran públicas, el55,4% desarrollaban actividad docente y el 53,6% eran multidisciplinares. El 72,4% de UDC eran mixtas. El89,3% eran dependientes del Servicio de Anestesiología. Sólo un 57,1% de UCD disponían de personal con dedicación exclusiva. La media del número de visitas anual por UDC fue de 2.194 (±2.041). Los recursos terapéuticos más utilizados fueron los fármacos, los bloqueos, las técnicas espinales y las técnicas de estimulación transcutáneas (TENS). Los sistemas implantables también fueron más frecuentes en las unidades de dolor crónico que en las de dolor mixto así como, también fue más frecuente en las universitarias que en las no universitarias (p= 0,03y p= 0,03 respectivamente). El abordaje psicológico se utilizó más en las multidisciplinares que en las unidisciplinarias (p<0,01). CONCLUSIONES: La distribución geográfica de las UDC en España no fue homogénea. La actividad asistencial de dichas UDC fue importante. Diversas características de las UDC como fuente de financiación, multidisciplinariedad, práctica de docencia universitaria y especialización en sólo dolor crónico, condicionaron la utilización de algunos tratamientos para el dolor

OBJECTIVES: To describe the characteristics and care approaches to care of chronic pain clinics operating in Spain in 2001.DESIGN: Cross-sectional mail survey of pain clinics in Spain. SETTING: Chronic pain clinics in Spain. STATISTICAL ANALYSIS: Descriptive statistics of pain clinics responding to the questionnaire. RESULTS: Fifty-six of the 79 pain clinics (70.8%) responded; 57.1% were in public facilities, 55.4% were affiliated with medical schools, and 53.6% were interdisciplinary units. Both acute and chronic pain were treated by 72.4%of the respondents. Anesthesiology departments supervised89.3% of the clinics. Only 57.1% had staff permanently assigned to the pain clinic. A mean 2194 (SD 2041) visits by patients were received annually. The most commonly applied treatments were drugs, blocks, spinal techniques, and transcutaneous electrical nerve stimulation. Implantable systems were more frequently used in chronic pain clinics than in mixed pain clinics, and in university-affiliated clinics than in non-teaching facilities (P=0.03 in both comparisons).A psychological approach was used more often in interdisciplinary clinics than in units operated by staff from a single specialty (P<0.01).CONCLUSIONS: Chronic pain clinics were not evenly distributed throughout Spain. The number of patients treated at pain clinics was high. The various characteristics of pain clinics—such as funding source, interdisciplinarity, university affiliation, and specialization in chronic pain—a were factors that affected the use of certain treatments