Venous Thromboembolism In Orthopedic Surgery Research Articles

Venous thromboembolism in orthopedic surgery: Global guidelines.

Venous thromboembolism (VTE) is a severe complication that can occur after major orthopedic procedures. As VTE-related morbidity and mortality are a significant concern for both medical professionals and patients, and preventative measures are typically employed. Multiple organizations, including the American College of Chest Physicians (ACCP) and the American Academy of Orthopedic Surgeons (AAOS), have developed guidelines for VTE prophylaxis specifically in patients undergoing joint replacement procedures. However, recently, the International Consensus Meeting (ICM) was convened, which brought together over 600 experts from 68 countries and 135 international societies. These experts, spanning a range of medical disciplines including orthopedic surgery, anesthesia, cardiology, hematology, vascular, and internal medicine, conducted a comprehensive review of the literature using a strict Delphi process to generate practical recommendations for VTE prophylaxis across all types of orthopedic procedures. This review article summarizes some of the recommendations of the ICM. Level of Evidence: Level V, Expert opinion.

Direct Oral Anticoagulants and Travel-related Venous Thromboembolism.

Travel- related thromboembolism reflects the relationship between venous thromboembolism (VTE) and long-haul flights. Although this condition is rare, it may cause significant morbidity and mortality. Therefore, travelers should be evaluated for the risks for thrombosis. Travel physicians should employ a clinical risk score and select in vestigations, prophylaxis, and treatment that are appropriate for each individual. This review summarizes current VTE clinical risk scores and patient management from various reliable guidelines. We summarized 16 reliable publications for reviewing data. Direct oral anticoagulants (DOACs) are currently the standard treatment for VTE and a prophylactic measure for VTE in orthopedic surgery. Compared with a vitamin K antagonist (VKA), DOACs show better safety and similar efficacy without the need for monitoring, and have fewer food/drug interactions. Inferred from the data on general VTE, DOACs may be used to treat travel-related VTE. Although the data are lacking, DOACs may be used off-label as VTE prophylax is. Before using DOACs, physicians must know the pharmacology of the drugs well and should realize that the availability of antidotes for bleeding complications is limited.

Venous thromboembolism prophylaxis after hip preservation surgery: a review and presentation of institutional experience.

ABSTRACTVenous thromboembolism (VTE) is a serious complication after major orthopedic procedures. The best options for prevention of the VTE are still debated. The most popular evidence-based guidelines for prevention and treatment of VTE in orthopedic surgery addressed the total hip or knee arthroplasty and hip fractures as the major orthopedic surgeries. Majority of studies have evaluated the different modalities of the VTE prophylaxis in patients undergiong hip or knee arthroplasty. Hip preservation surgeries (HPS) including mini-open femoroacetabular osteoplasty, surgical dislocation of the hip, arthroscopic procedures, and periacetabular osteotomy (PAO) are gained popularity in recent two decades. The majority of these patients are young, healthy and active and may not be considered at high risk for VTE. The frequency of VTE in patients undergoing PAO seems to be low between 0 and 5%. There is a paucity of data regarding rates of VTE in young healthy patients undergoing HPS as well as the optimal prevention methods for VTE. Hence current VTE prevention guidelines do not cover HPS adequately. We aimed to review the available literature regarding VTE events and VTE prophylaxis options after HPS. We discussed the available and potential options for prophylaxis of VTE events in these procedures along with our experience in a large cohort of hip preservation surgery.

Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis

BackgroundThere is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopaedic surgery and in patients suffering non-surgical trauma. MethodsWe used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopaedic procedures and in trauma patients not requiring surgery. ResultsFrom March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1045 (1.69%) after non-major orthopaedic surgery and 2136 (3.46%) after non-surgical trauma. Overall, 2283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45–0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n=9 [2.02%]) than after elective arthroplasty (n=5 [0.53%]), non-major orthopaedic surgery (n=5 [0.48%]) or non surgical trauma (n=11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopaedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopaedic surgery (1.5%) or non-surgical trauma (1.4%). ConclusionsThromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopaedic surgery or non-surgical trauma, exceeded that observed after high risk procedures.

Major Bleeding and Case Fatality Rate with the Direct Oral Anticoagulants in Orthopedic Surgery: A Systematic Review and Meta-Analysis.

The novel direct oral anticoagulants (DOACs) have been proposed as alternatives to low-molecular-weight heparins (LMWHs) for the prevention of venous thromboembolism in orthopedic surgery. However, the clinical impact of postsurgical bleeding with the DOACs has not been extensively evaluated. MEDLINE and EMBASE databases, supplemented with conference abstract books and www.clinicaltrial.gov, were searched up to the first week of March 2015. We included phase II and phase III randomized controlled trials comparing the DOACs with LMWHs in patients undergoing major orthopedic surgery. Data regarding major, fatal, and intracranial bleeding were collected, to calculate the pooled relative risk (RR) and the case-fatality rate (CFR), with 95% confidence interval (CI). We retrieved 25 studies (5 evaluating dabigatran, 4 apixaban, 6 edoxaban, and 10 rivaroxaban), enrolling 42,170 patients. There was no significant difference between the DOACs and LMWHs in the risk of major (1.23 vs. 1.16%; RR: 1.07, 95% CI: 0.89-1.29), fatal (0.02 vs. 0.01%; RR: 1.63, 95% CI: 0.39-6.77), and intracranial bleeding (0 vs. 0.01%; RR: 0.33, 95% CI: 0.03-3.18). The weighted mean CFR of major bleeding was 3.3% (95% CI, 1.5-5.7) and 2.3% (95% CI, 0.7-4.6), respectively. Bleeding complications and the associated CFR during prophylactic anticoagulation in orthopedic surgery were very low and not significantly different between the DOACs and LMWHs.

Testing the therapeutic equivalence of novel oral anticoagulants for thromboprophylaxis in orthopedic surgery and for prevention of stroke in atrial fibrillation.

In studying the comparative effectiveness of novel oral anticoagulants (NOACs) in orthopedic surgery and in non-valvular atrial fibrillation, previous meta-analyses have found no proof of difference in head-to-head indirect comparisons between individual agents. However, the question of their therapeutic equivalence remains unanswered. The objective of this analysis was to test the equivalence of three NOACs (dabigatran, rivaroxaban, apixaban) in orthopedic surgery and four NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) in non-valvular atrial fibrillation. Standard pairwise meta-analysis and network meta-analysis for indirect comparisons were combined with equivalence testing. The endpoint was venous thromboembolism in orthopedic surgery and a composite of stroke or systemic embolism in atrial fibrillation. Comparisons were expressed as risk difference (RD). Margins for equivalence testing were derived from the original trials. Our results indicate that rivaroxaban and apixaban (but not dabigatran) are equivalent for thromboprophylaxis in orthopedic surgery. In atrial fibrillation, all the four NOACs we tested were found to meet the criterion of therapeutic equivalence. Some concern, however, is raised by some findings focused on adverse events of these agents, in which the equivalence was not proven in all analyses. Regardless of clinical implications, our results can be the basis to develop local acquisition tenderings on NOACS. In Italy, a new law has been issued according to which equivalence analyses have become a mandatory prerequisite for local tenderings.

Pharmacological prevention of venous thromboembolism in orthopaedic surgery

The prophylaxis of venous thromboembolism (VTE) with anticoagulant drugs is a long-established practice in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures, while there are few data regarding the prevention of VTE in other fields of orthopaedic surgery and traumatology. In order to provide practical recommendations for daily management of VTE prophylaxis in orthopaedic patients, recently the Italian Societies of Thrombosis and Haemostasis, Orthopaedics and Traumatology and Anaesthesia have drawn up a first Intersociety Consensus on antithrombotic prophylaxis in total hip and knee replacement surgery, and in the treatment of femoral neck fracture, then updated in 2013, and a subsequent Intersocietary Consensus, in cooperation also with the Society of general practitioners, concerning antithrombotic prophylaxis in other types of orthopaedic surgery and traumatology. Before starting any prophylactic treatment it is of crucial importance the assessment of both thrombotic and bleeding risk of patients undergoing surgery. Thromboembolic prophylaxis is recommended with low molecular weight heparins (LMWH), fondaparinux (FON) or with the new oral anticoagulants (NOA) in patients undergoing hip and knee replacement surgery while patients undergoing treatment of femoral neck fracture should be treated with LMWH or FON. Regarding the non-prosthetic orthopaedic surgery and traumatology, it is recommended prophylaxis with LMWH or FON in situations of high thromboembolic risk or in the case of interventions or trauma involving pelvis, acetabulum or knee.

OHP-068 Repeat Audit of LMWH Use in Thromboprophylaxis on an Orthopaedic Surgery Ward, Emergency Centre, Belgrade

BackgroundThe Guideline for Prevention of Deep Venous Thromboembolism in Orthopedic Surgery, based on current European and American Guidelines, was introduced in late 2009 on the Orthopedic Surgery Ward, Emergency Centre,...

TB-402 for the prevention of venous thromboembolism in orthopaedic surgery: Something new and promising, or not?

TB-402 for the prevention of venous thromboembolism in orthopaedic surgery: Something new and promising, or not? -

Systematic review and meta-analysis on the rate of postoperative venous thromboembolism in orthopaedic surgery in Asian patients without thromboprophylaxis

Postoperative venous thromboembolism (VTE) is a common life-threatening complication after surgery. This review analysed the rate and mortality of VTE after orthopaedic surgery in Asia. Inclusion criteria were: prospective study; deep vein thrombosis (DVT) diagnosed by venography or ultrasonography; hip fracture surgery (HFS), total hip arthroplasty (THA) or total knee arthroplasty (TKA); and no thromboprophylaxis. The pooled proportion was back-calculated by Freeman-Tukey variant transformation, using a random-effects model. Twenty-two studies (total population 2454) published from 1979 to 2009 were included. Using venography, the pooled rates of all-site, proximal, distal and isolated distal DVT were 31·7, 8·9, 22·5 and 18·8 per cent respectively. With duplex ultrasonography, the respective rates were 9·4, 5·9, 5·9 and 5·8 per cent. After THA or HFS, using venography, the pooled rates of all-site and proximal DVT were 25·8 and 9·6 per cent; with ultrasonography, the respective rates were 10·8 and 7·2 per cent. In TKA groups, using venography, the pooled rates of all-site and proximal DVT were 42·5 and 8·7 per cent; with ultrasonography, the respective rates were 9·5 and 5·2 per cent. The overall pooled rates of symptomatic DVT and symptomatic pulmonary embolism (PE) were 4·5 and 0·6 per cent. No patient died from PE (pooled rate 0·2 per cent). None of these Asian patients undergoing orthopaedic surgery died from VTE. Pooled rates of proximal and symptomatic DVT were lower than in Western reports.

A Benefit-Risk Assessment of Dabigatran in the Prevention of Venous Thromboembolism in Orthopaedic Surgery

Dabigatran etexilate is a novel orally administered anticoagulant that exerts its action through reversible direct thrombin inhibition. This anticoagulant has been approved for prophylaxis against venous thromboembolism (VTE) after hip or knee arthroplasty, and in a few countries also for atrial fibrillation. This article reviews the efficacy and safety of dabigatran for the prophylaxis of VTE-indication compared with data on the most common current regimen with low-molecular-weight heparin (LMWH), specifically enoxaparin. Alternative prophylactic agents are also discussed. The results regarding efficacy and safety are very similar for dabigatran and LMWH. Bleeding and gastrointestinal reactions are the most frequently reported adverse events with a comparable incidence on LMWH and are probably the result of surgery and anaesthaesia. No adverse event that is specific for dabigatran has been observed in these studies, although dyspepsia has been reported as significantly more frequent than warfarin in long-term studies on other indications. The fact that dabigatran has no antidote has so far not been a problem in patients undergoing orthopaedic surgery. The use of the lower dose of dabigatran (150 mg) appears beneficial to reduce the risk of bleeding in patients over 75 years of age and in those with moderate renal impairment to avoid drug accumulation. The convenience of oral administration is an advantage for dabigatran over LMWH, particularly for extended prophylaxis up to 1 month after surgery. In conclusion, the benefit-risk profile of dabigatran is favourable for use as prophylaxis against VTE after major orthopaedic surgery with its convenient oral administration without need for laboratory monitoring and a low risk of bleeding or other adverse events.

Further Issues with New Oral Anticoagulants

In recent years new oral anticoagulants have been evaluated in the prevention of venous thromboembolism (VTE) after elective hip or knee arthroplasty, atrial fibrillation to prevent ischemic stroke and in the treatment of acute VTE. While two oral anticoagulants, dabigatran and rivaroxaban, have become available for the prevention of VTE in orthopaedic surgery, other indications still are under evaluation or await approval. There are also areas where these novel drugs have not yet been evaluated. These include patients with acute VTE and cancer, pregnant patients with acute VTE and patient with either rheumatic heart valve disease or artificial heart valves. Finally, in acute care settings, where anticoagulant reversibility is critical, such as during and after coronary artery bypass surgery or acute PCI setting in patients with high bleeding risk, novel intravenous anticoagulant drugs with either short half life or specific antidotes may have added value. This article will focus on these unresolved issues.

Emerging anticoagulants for venous thromboembolism prevention

To discuss the advantages and disadvantages of currently available anticoagulants, describe the characteristics of the ideal anticoagulant, and compare and contrast the mechanisms of action, pharmacokinetics, administration, efficacy, safety, and potential for drug interactions of currently available and emerging anticoagulants for prevention of venous thromboembolism (VTE). Despite the proven efficacy of currently available agents for VTE prevention, several shortcomings exist that may prevent their use under various circumstances. These include administration by injection, narrow therapeutic index, unpredictable pharmacokinetics and pharmacodynamics, need for laboratory monitoring, risk for bleeding, and drug interactions. The ideal anticoagulant would overcome many of these issues; in particular, it would be available as an oral formulation. Dabigatran, an oral direct thrombin (factor IIa) inhibitor, and apixaban and rivaroxaban, oral direct factor Xa inhibitors, represent new agents for anticoagulation that may address many of these issues. While not available as an oral agent, desirudin is an additional option and offers increased flexibility when a non-heparin-based injectable anticoagulant is desired. Current literature indicates that these agents generally do not require laboratory monitoring and are safe and effective for VTE prevention in clinical studies of patients undergoing major orthopedic surgery. The development of new anticoagulants that may overcome limitations of existing agents represents an opportunity to further improve outcomes in patients at risk for VTE in orthopedic surgery.

The impact of national guidelines for the prophylaxis of venous thromboembolism on the complications of arthroplasty of the lower limb

The National Institute for Clinical Excellence (NICE) produces recommendations on appropriate treatment within the National Health Service (NHS) in England and Wales. The NICE guidelines on prophylaxis for venous thromboembolism in orthopaedic surgery recommend that all patients be offered a low molecular weight heparin (LMWH). The linked hospital episode statistics of 219 602 patients were examined to determine the rates of complications following lower limb arthroplasty for the 12-month periods prior to and following the publication of these guidelines. These were compared with data from the National Joint Registry (England and Wales) regarding the use of LMWH during the same periods. There was a significant increase in the reported use of LMWH (59.5% to 67.6%, p < 0.001) following the publication of the guidelines. However, the 90-day venous thromboembolism events actually increased slightly following total hip replacement (THR, 1.69% to 1.84%, p = 0.06) and remained unchanged following total knee replacement (TKR, 1.99% to 2.04%). Return to theatre in the first 30 days for infection did not show significant changes. There was an increase in the number of patients diagnosed with thrombocytopenia, which was significant following THR (0.11% to 0.16%, p = 0.04). The recommendations from NICE are based on predicted reductions in venous thromboembolism events, reducing morbidity, mortality and costs to the NHS. The early results in orthopaedic patients do not support these predictions, but do show an increase in complications.

A randomized phase II trial of a new anticoagulant, apixaban, in metastatic cancer

e20514 Background: Cancer patients receiving chemotherapy, biologic, and molecular targeted therapies are at increased risk of venous thromboembolism (VTE). Currently available anticoagulants (ACs) are not well suited to prevent VTE in such patients. Vitamin K antagonist oral ACs require frequent lab monitoring and low molecular weight heparins require daily subcutaneous injection. There is concern for bleeding with ACs. Apixaban (A) is a new antithrombotic agent which inhibits activated coagulation Factor X, is taken orally, and does not require lab monitoring. Trials to prevent post-operative VTE in orthopedic surgery showed that A was effective and safe. We wanted to assess the feasibility of A in cancer. Methods: In a randomized phase II trial, patients with metastatic cancer on 1st or 2nd line chemotherapy received study drug once daily for 12 weeks; either 5, 10 or 20 mg of A, or placebo. The primary outcome measure was the proportion of patients remaining free of major bleeding (MB), clinically relevant non-major bleeding (CRNMB), VTE, and grade ≥3 adverse events considered to be probably/definitely related to study drug (AE*). After 125 patients were recruited, the sponsor eliminated further randomization to the 10 and 20 mg arms, to add experience with the 5 mg dose currently under evaluation for VTE prevention in other conditions. Data on the first 125 patients are reported. Results: The study population was 50% male; 88% had ECOG performance status 0 or 1. The most common cancers were breast, colon, pancreas, and myeloma. 23% had liver metastases. Approximately 80% of A patients completed 12 weeks of treatment. The numbers of patients with events were: Conclusions: Apixiban was well tolerated in patients with advanced cancer on chemotherapy. Major bleeding, thrombosis, and drug-related SAEs were very low. These results support further study of A in phase III trials for VTE prevention in cancer patients. [Table: see text] [Table: see text]

Anesthesia and Orthopaedic Surgery.

Anesthesia and Orthopaedic Surgery.

Animal Models of Thrombosis Help Predict the Human Therapeutic Concentration of PRT54021, a Potent Oral Factor Xa Inhibitor.

Factor Xa (fXa) inhibition has resulted in the emergence of a new class of antithrombotics. Pharmacodynamic monitoring of these agents has proven problematic. The present study was designed todetermine the target concentration of an oral fXa inhibitor required for clinical trials using both thrombin generation assays and three in vivo models anddetermine whether clotting assays such as activated partial thromboplastin time (aPTT) and prothrombin time (PT) would be suitable for monitoring human dosing.PRT54021 (PRT021) is a potent inhibitor of human fXa (Ki=117pM). PRT021 and fondaparinux, an indirect fXa inhibitor, both significantly inhibited TAT and F1.2 generation in human whole blood. Compared to a therapeutic level of fondaparinux (200nM), PRT021 (200nM) was more potent in suppressing both markers. Multiple doses of PRT021 were evaluated in three animal models. The first model, which measured clot accretion on cotton threads placed in rabbit abdominal vena cava, compared inhibition of thrombus mass by PRT021 to that of supratherapeutic doses of enoxaparin (a LMW heparin). The second model compared the ability of PRT021 to maintain vessel patency under arterial flow conditions in FeCl3 induced thrombosis in rat carotid artery to that achieved by enoxaparin or clopidogrel (an antiplatelet agent). The third model investigated inhibition of 111In labeled platelet deposition on dacron grafts and expansion chambers placed in femoral arteriovenous shunts in baboons. PRT021 and enoxaparin were administered as IV infusions and clopidogrel was dosed orally for three days. Ex vivo PT and aPTT were measured in all models. The models encompass stringent criteria of arterial and venous thrombosis and PRT021 produced dose-responsive antithrombotic activity in each of the three models. The efficacy of PRT021 compared favorably to supratherapeutic levels of enoxaparin and clopidogrel. Unlike in the rodent models, efficacy in primates was attained at a much lower dose with minimal prolongation of PT. Species specificity was also demonstrated by in vitro extensions of PT and aPTT in rat, rabbit, baboon and human plasma. A 2X change of PT was attained at concentrations of 8.9, 1.6, 1 and 0.4μM respectively. The data indicate that doses of PRT021 that inhibit thrombin generation in human blood and that provide anticoagulation similar to baboon dosed at 0.49mg/kg may be sufficient to prevent venous thrombosis in humans. Comparative modeling of extents of change in PT to levels of antithrombotic efficacy also leads us to predict that human therapeutic activity for PRT021 may be attained without concurrent changes in ex vivo clotting parameters. The targeted concentration is currently being tested in Phase II trials for its ability to prevent venous thromboembolism in orthopedic surgery patients.Model of ThrombosisAgent, DoseAntithrombotic ActivityaPTT fold changePT fold changeRabbit vena cavaPRT021,3mg/kg76% inhibition2.222.34Rabbit vena cavaEnoxaparin, 1.6mg/kg96% inhibition2.062.01Rat carotidPRT021,19.1mg/kg90% patency1.692.20Rat carotidEnoxaparin, 7.6mg/kg70% patency3.491.19Rat carotidClopidogrel, 3mg/kg/day80% patency1.031.01Baboon arteriovenousPRT021,0.49mg/kg90% inhibition (venous), 32% inhibition (arterial)1.291.17

Choosing the Appropriate Antithrombotic Agent for the Prevention and Treatment of VTE: A Case-Based Approach

To review the risk of venous thromboembolism (VTE) in various patient populations and evaluate the agents available for the prevention and treatment of VTE using a case-based approach. A MEDLINE search (1995-July 2006) was conducted to identify relevant literature. Additional references were reviewed from selected articles. Articles related to the prevention of VTE in orthopedic surgery, general surgery, and medically ill patients, as well as the treatment of VTE, were reviewed. Pharmacologic options for the prevention and treatment of VTE include warfarin, unfractionated heparin (UFH), low-molecular-weight heparins (LMWH), and fondaparinux. Current guidelines support the use of warfarin, LMWH, or fondaparinux for VTE prophylaxis following lower limb major orthopedic surgery. For VTE prophylaxis in hospitalized medical patients or patients undergoing general surgery, use of UFH and LMWH is supported; however, recent data on fondaparinux suggest that it is also effective in these patient populations. The use of UFH or LMWH (both in conjunction with warfarin) for treatment of acute deep venous thrombosis or nonmassive pulmonary embolism is recommended. Recent data suggest that fondaparinux (in conjunction with warfarin) is also effective for the treatment of VTE. A variety of pharmacokinetic, pharmacodynamic, and pharmacoeconomic factors differentiate each agent for the various indications. Currently, a "one-size-fits-all" anticoagulant is not available for treatment of VTE. A variety of patient factors, including type of surgery, medical indication, thrombotic risk factors, bleeding risk, history of heparin-induced thrombocytopenia, and a variety of comorbid conditions can affect the safety, efficacy, and selection of appropriate VTE therapy.

Flexibility in Administration of Fondaparinux for Prevention of Symptomatic Venous Thromboembolism in Orthopaedic Surgery

Venous thromboembolism (VTE) is a common complication of total joint arthroplasty. Fondaparinux VTE prophylaxis is currently begun 6 to 8 hours after surgery. Flexible dosing may reduce bleeding risk and allow easier use by starting the morning after surgery instead of staggered hours on the surgery day. This study examined flexible timing of the first dose of fondaparinux. Whether the first dose was administered 8 ± 2 hours after surgery or the morning after surgery, no significant difference was observed in incidence of symptomatic VTE (2.0% and 1.9%, respectively, P = .89). Major and minor bleeding events were similar between groups (1.2% and 0.7% [ P = .19], and 1.4% and 2.0% [ P = .31], respectively). Delaying initiation of fondaparinux prophylaxis provides an option after total joint arthroplasty with preserved efficacy and safety.

Treatment of Venous Thromboembolism in Orthopaedic Surgery

Summary:The mainstay of treatment for deep venous thrombosis and pulmonary embolism for the last 40 years has been adjusted-dosage intravenous heparin. Newer products that are administered as fixed dosing and other drugs that do not require frequent monitoring are discussed. This article is tailored