Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials.

BACKGROUND: Three randomized, double-blind trials compared dabigatran, an oral direct thrombin inhibitor, with enoxaparin for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty. OBJECTIVES AND METHODS: We conducted a pre-specified pooled analysis of these trials. 8,210 patients were randomized, of whom 8,135 were treated (evaluable for safety) with dabigatran 220 mg or 150 mg once-daily, or subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily). Efficacy analyses were based on the modified intention-to-treat population of 6,200 patients with an evaluable outcome. The common risk difference (RD) of treatment effect between each dabigatran dose and enoxaparin was estimated using fixed-effects models, and statistical heterogeneity was estimated using the I2 statistic. RESULTS: The composite outcome of major VTE (proximal deep vein thrombosis and/or pulmonary embolism) and VTE-related mortality occurred in 3.3% of the enoxaparin group versus 3.0% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, 95% CI -1.3% to 0.9%, I2=37%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%, I2=0%). Major bleeding occurred in 1.4% of the enoxaparin group versus 1.4% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, -0.8% to 0.5%, I2=40%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%, I2=0%). CONCLUSIONS: Oral dabigatran was as effective as subcutaneous enoxaparin in reducing the risk of major VTE and VTE-related mortality after hip or knee arthroplasty and has a similar bleeding profile.

Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use.

AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.

Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry.

Patients who have undergone total hip or knee replacement (THR and TKR, respectively) are at high risk of venous thromboembolism. We aimed to determine the time courses of both the incidence of venous thromboembolism and effective prophylaxis. Patients with elective primary THR and TKR were enrolled in the multi-national Global Orthopaedic Registry. Data on the incidence of venous thromboembolism and prophylaxis were collected from 6639 THR and 8326 TKR patients. The cumulative incidence of venous thromboembolism within three months of surgery was 1.7% in the THR and 2.3% in the TKR patients. The mean times to venous thromboembolism were 21.5 days (sd 22.5) for THR, and 9.7 days (sd 14.1) for TKR. It occurred after the median time to discharge in 75% of the THR and 57% of the TKA patients who developed venous thromboembolism. Of those who received recommended forms of prophylaxis, approximately one-quarter (26% of THR and 27% of TKR patients) were not receiving it seven days after surgery, the minimum duration recommended at the time of the study. The risk of venous thromboembolism extends beyond the usual period of hospitalisation, while the duration of prophylaxis is often shorter than this. Practices should be re-assessed to ensure that patients receive appropriate durations of prophylaxis.

Regaining chondrocyte phenotype in thermosensitive gel culture.

Chondrocyte tissue engineering continues to be a challenging problem. When chondrocytes are duplicated in vitro, it is imperative to obtain an adequate number of cells of optimal phenotype. A temperature-sensitive polymer gel, a copolymer of poly(N-isopropylacrylamide) and acrylic acid (PNiPAAm-co-Aac), has the ability of gelling at 37 degrees C (the lower critical solution temperature, LCST) or above and liquefying below that temperature (Vernon and Gutowska, Macromol. Symp. 1996;109:155-167). The hypothesis of this study was that chondrocytes could (1) duplicate in the copolymer gel; (2) regain their chondrocyte phenotype; and (3) be easily recovered from the gel by simply lowering the temperature below 37 degrees C. Chondrocytes from adult rabbit scapular cartilage were harvested and cultured in a monolayer culture until confluency (approximately 2 weeks). Next, the cells were harvested and seeded into the copolymer gel and cultured for 2-4 weeks. The phenotype of the cultured cells was then characterized. Two groups of control cultures, monolayer and agarose gel, were used to compare their ability to maintain chondrocyte phenotype. The results showed that chondrocytes isolated from rabbit scapula can re-express chondrocyte phenotype in agarose culture and polymer gel culture but not in monolayer culture. Also, cultured chondrocytes can be easily recovered from polymer gel culture by simply lowering the temperature. This new in vitro method of chondrocyte culture is recommended for chondrocyte propagation and regaining chondrocyte phenotype before cell seeding or transplantation.

Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group.

BACKGROUND: Patients undergoing hip or knee joint replacement are at risk for venous thromboembolic complications for up to twelve weeks postoperatively. We evaluated the efficacy and safety of a prolonged post-hospital regimen of enoxaparin, a low-molecular-weight heparin, in this patient population. METHODS: Following elective total hip or knee replacement, 968 patients received subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, and 873 were then randomized to receive three weeks of double-blind outpatient treatment with either enoxaparin (40 mg once daily) or a placebo. The primary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind phase of treatment. RESULTS: Of the 873 randomized patients, 435 underwent elective total hip replacement and 438 underwent elective total knee replacement. Enoxaparin was superior to the placebo in reducing the prevalence of venous thromboembolism in patients treated with hip replacement: 8.0% (eighteen) of the 224 patients treated with enoxaparin had venous thromboembolism compared with 23.2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; odds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduction, 65.5%). Enoxaparin had no significant benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated with enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Symptomatic pulmonary embolism developed in three patients, one with a hip replacement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups. CONCLUSIONS: Prolonging enoxaparin thromboprophylaxis following hip replacement for a total of four weeks provided therapeutic benefit, by reducing the prevalence of venous thromboembolism, without compromising safety. A similar benefit was not observed in patients treated with knee replacement.

Evaluation of scatter contribution from shielding materials used in scatter measurements for calibration range characterization.

The contribution of scatter from the shielding material used in scatter measurements at the Ohio Emergency Management Agency was evaluated. This was accomplished by comparing physical measurements with results generated by detectors modeled in the Monte Carlo shielding code, MCNP4B. The high purity germanium (HPGe) detector model was improved by using radiographs to more accurately represent the detector geometry, including a model of the lithium-contact transition region, and considering the effects of the non-uniform electric field in the germanium crystal. Photons scattered from the shielding material were found to contribute 4.25% of the total scatter recorded by the HPGe detector (thus contributing only 0.26% of the total dose) at a point 5 m from a 1.35 GBq (36.4 mCi) 137Cs source.

Pre-clinical in vivo evaluation of orthopaedic bioabsorbable devices.

The presence of bioabsorbable materials in orthopaedics has grown significantly over the past two decades with applications in fracture fixation, bone replacement, cartilage repair, meniscal repair, fixation of ligaments, and drug delivery. Numerous biocompatible, biodegradable polymers are now available for both experimental and clinical use. Not surprisingly, there have been a wealth of studies investigating the biomechanical properties, biocompatibility, degradation characteristics, osteoconductivity, potential toxicity, and histologic effects of various materials. Promising results have been reported in the areas of fracture fixation, ligament repair, and drug delivery. In this article we review the pre-clinical in vivo testing of bioabsorbable devices with particular emphasis on implants used for these applications.

Complete brachial plexus palsy after total shoulder arthroplasty done with interscalene block anesthesia.

BACKGROUND AND OBJECTIVES: This report illustrates that brachial plexus palsy can result from either interscalene block or total shoulder arthroplasty. It is often impossible to determine which procedure caused the deficit; therefore, we believe the focus should be placed on treatment of the neurologic deficit. This report provides a suggested algorithm for diagnosis and treatment of postprocedure brachial plexus palsy. METHODS: Interscalene block was used as the operative anesthetic for our patient's total shoulder arthroplasty. Complete brachial plexus palsy was diagnosed postoperatively. RESULTS: The patient's postoperative treatment and recovery are described. CONCLUSIONS: Proper diagnosis and treatment of postprocedure brachial plexus palsy may improve recovery of function. Several precautions may reduce the likelihood of brachial plexus palsy following interscalene block for total shoulder arthroplasty.

Intersubjectivity and interaction in the analytic relationship: a mainstream view.

The authors conceptualize intersubjectivity as a meta-theory that reflects the inherent nature of human relatedness and is conceptually independent of any particular theory of mind or school of psychoanalysis. Their view of intersubjectivity joins the emotional life of the analyst to that of the patient and places the analytic relationship at the center of the analytic process. They contrast intersubjectivity with traditional classical conflict theory so as to clarify the relevance of intersubjectivity for psychoanalytic clinical theory and therapeutic practice. In so doing, they hope to direct analysts more firmly toward the study of the unconscious dyadic contributions to the affective, inactive, and interactive dimensions of the analytic situation and their impact upon the patient's actions within and experience of the analytic relationship. To illustrate their thesis, two hours from an analysis are presented in detail.

Multidirectional instability of the glenohumeral joint.

The concept of multidirectional instability (MDI) was introduced as an important clinical entity in 1980. Previously, it had received little mention in the literature and was not considered to be clinically relevant. MDI is a symptomatic glenohumeral subluxation or dislocation occurring in more than one direction. The basic pathology of this condition is a loose and redundant joint capsule. Most patients with MDI can be treated successfully by conservative methods, such as patient education, a shoulder girdle strengthening program, or modification of the patient's routine activity.

Cost analyses of extended prophylaxis with enoxaparin after hip arthroplasty.

Venous thromboembolic complications occur in 50% to 70% of patients undergoing total hip arthroplasty if no prophylactic regimen is used. Because enoxaparin and warfarin are useful for extended outpatient prophylaxis, the objective of this study was to determine which of these agents is most cost effective in preventing venous thromboembolic complications. A decision tree analysis was developed to simulate a hypothetical cohort of patients with total hip arthroplasty. The analysis considered home health care services to perform monitoring and compliance verification. Accounting for prophylactic failures and treatment complications, results showed that enoxaparin maintained a cost effective advantage over warfarin for extended prophylaxis in the time after discharge and total hip arthroplasty ranging from 19 to 31 days after the patient was discharged from the hospital. The duration of cost effectiveness of enoxaparin was reduced to 14 to 17 days when home care services were excluded. These results indicated that approximately 3 weeks of outpatient therapy with enoxaparin is cost effective. With the cornerstone of managed care being cost efficiency in the provision of quality care, this conclusion warrants the development of integrated care strategies for the patient having orthopaedic surgery to achieve cost effective patient management.

Hydroxyapatite composites designed for antibiotic drug delivery and bone reconstruction: a caprine model.

The purpose of this study was to investigate the feasibility of fabricating a drug delivery system that serves a dual function, to eradicate infection as well as to provide a scaffold for osseous integration. Two porous composite systems were fabricated using hydroxyapatite (HA) as the carrier for gentamicin sulfate (GS), an aminoglycoside antibiotic. Structural and mechanical properties of porous HA-GS composites were characterized and the in vitro release behavior of GS from fabricated composites was monitored and compared with the well-known polymethylmethacrylate (PMMA)-GS delivery system. Scanning electron microscopy revealed a macropore range of 150 to 200 microm and 100 to 190 microm for the sintered and unsintered HA-GS composites, respectively. The effect of GS inclusion on bone apposition and ingrowth was assessed using a caprine model. Plugs 10 mm x 6 mm of cylindrical tricalcium phosphate, sintered HA, and sintered HA-GS were implanted in the femoral diaphysis for a period of 6 weeks. Data collected during the in vitro study showed that GS can successfully be incorporated into HA and used as a drug delivery system to eradicate Staphylococcus aureus. In vivo data confirmed that the inclusion of GS within a ceramic matrix did not stimulate or inhibit osteointegration or bone apposition. In conclusion, the fabricated sintered HA-GS composite may be beneficial in the treatment of infected osseous sites as a drug delivery system.

A standardized method for assessment of elbow function. Research Committee, American Shoulder and Elbow Surgeons.

The American Shoulder and Elbow Surgeons have adopted a standardized form for assessment of the elbow. This form was developed by the Research Committee of the American Shoulder and Elbow Surgeons and subsequently adopted by the membership. The patient self-evaluation section contains visual analog scales for pain and a series of questions relating to function of the extremity. The responses to the questions are scored on a 4-point ordinal scale. The physician assessment section has 4 parts: motion, stability, strength, and physical findings. It is hoped that adoption of this method of data collection will stimulate multicenter studies and improve communication between professionals who assess and treat patients with elbow disorders.

Enactments: an intersubjective perspective.

We offer a critique and synthesis of classical and interpersonal views of enactment. From an intersubjective standpoint, the study of enactment leads to a reconsideration of the nature of the psychoanalytic process. And enactment becomes virtually synonymous with the psychoanalytic process. Enactments are interactions of analysand and analyst with communicative and resistive meanings that lead to valuable insight and can constitute corrective emotional experiences. Enactments that are recognized and defined become valuable dramatizing moments that have condensing, clarifying, and intensifying effects upon consciousness. The inevitable participation by the analyst in enactment is compatible with appropriate analytic discipline. A case will demonstrate these points.

The role of low molecular weight heparin in total knee arthroplasty.

Low-molecular-weight heparin prophylaxis is an acceptable, if not superior, alternative to heparin and warfarin prophylaxis in TKA. Considering the current popularity of pharmacologic prophylaxis after total hip and total knee arthroplasty and the advantages of low-molecular-weight heparins over traditional pharmacologic agents, these agents have the potential to become the prophylactic agent of choice against DVT in TKA. There are several practical differences between low molecular weight heparins and warfarin. Low molecular weight heparins are administered by subcutaneous injection and do not require drug-level or blood monitoring. Warfarin, although administered orally, must be maintained within an appropriate international normalized ratio (INR=2-3) with daily dose adjustments and takes 36 hours to produce a measurable effect, which may leave patients relatively unprotected during the early postoperative period. Comparative trials have demonstrated that low molecular weight heparins are more efficacious than warfarin in producing a greater overall reduction in the incidence and risk of DVT, but show similar rates of PE. Some studies suggest that bleeding may be a greater problem with low molecular weight heparin. Despite the superior efficacy of low molecular weight heparin, the prevalence of venous thromboembolism after TKA continues to be substantial compared with total hip arthroplasty, with at least a quarter of patients still affected. Additional prophylaxis strategies for this indication are needed and could include combining mechanical prophylaxis (eg, external pneumatic compression) with low molecular weight heparin. An appropriate management strategy should be established for all patients undergoing TKA. This should include identification of high-risk patients, cautious transfusion of blood products, pharmacologic prophylaxis with an acceptable agent for TKA, early mobilization, postoperative screening in high-risk patients, and continuing pharmacologic prophylaxis for an appropriate period postoperatively.

Bone ingrowth to implant surfaces in an inflammatory arthritis model.

Many studies have shown enhanced bone apposition to implants coated with hydroxyapatite, but the optimum implant texture, especially in abnormal trabecular bone, is unclear. The purpose of this project was to evaluate the histological and mechanical properties of cylindrical implants with three different surface textures that were placed in the cancellous bone of the distal femur of the rabbit after the production of an inflammatory knee arthritis. The three implant surfaces included a beaded surface (Group A), a beaded surface coated with hydroxyapatite (Group B), and a smooth surface coated with hydroxyapatite (Group C). The right knees of 36 rabbits were injected with carrageenan twice a week for 2 weeks. Then bilateral implantations were performed, with 12 rabbits in each group receiving identical implants in the right and left knees. The rabbits were killed 6 weeks after surgery. Mechanical (push-out test) and histomorphometric analyses were performed to determine the quality and quantity of bone ingrowth. In Group A, there was virtually no direct contact (a 20-60-microm clearance) between the bone and the beaded surfaces. Direct contact between the bone and the implant surfaces was seen in Groups B and C. The thickness and number of trabeculae were smaller on the arthritic side than on the control side for all groups but were not different between groups for either the control or the arthritic side. Mechanical testing showed that the shear strength of the interface was weaker on the arthritic side in all groups. The results suggest that inflammatory arthritis induced by carrageenan may influence the quality of local bone (osteopenic changes) and hence compromise the bone apposition and mechanical stability of the interface between the implant and bone.

[Instability of the sternoclavicular joint]. / Die Instabilität des Sternoklavikulargelenks.

Instability of the sternoclavicular joint is a rare diagnosis and will mostly be found after motor vehicle accidents or sports injuries. Depending on the severity of the trauma open reduction is rarely required, and most cases will be treated successfully with conservative management. Associated injuries to the surrounding anatomic structures are not rare, and can be found in posteriorly directed injuries.

Concise review of mechanisms of bacterial adhesion to biomaterial surfaces.

This article reviews the mechanisms of bacterial adhesion to biomaterial surfaces and the factors affecting the adhesion. The process of bacterial adhesion includes an initial physicochemical interaction phase (phase one) and a late molecular and cellular interaction phase (phase two), which is a complicated process affected by many factors, including the characteristics of the bacteria themselves, the target material surface, and the environmental factors, such as the presence of serum proteins or bactericidal substances.

Humeral technique in total shoulder arthroplasty.

Humeral head replacement arthroplasty has been performed for more than 40 years. As the technique has been refined and advances have been made in joint arthroplasty of the lower extremity, the indications and success of shoulder arthroplasty have greatly improved. The humeral component in a shoulder arthroplasty can be implanted with either cement or press fit fixation. Both techniques are precise and demand meticulous attention to detail to achieve optimum results for the patient. Press fit fixation, with or without porous coating for biologic ingrowth, can be considered for a patient with good bone stock, if it is felt that a stable interface can be obtained. In patients with abnormal bone, such as those with rheumatoid arthritis who are on corticosteroids and those with osteoporosis, the use of cement can provide stable long-term fixation.