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.

Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study.

BACKGROUND: Up to one third of patients who undergo total knee replacement develop deep vein thrombosis after surgery despite receiving low-molecular-weight heparin prophylaxis. Ximelagatran is a novel direct inhibitor of free and clot-bound thrombin. METHODS: We performed a randomized, parallel, dose-finding study of 600 adults undergoing elective total knee replacement at 68 North American hospitals to determine the optimum dose of ximelagatran to use as prophylaxis against venous thromboembolism after total knee replacement. Patients received either ximelagatran twice daily by mouth in blinded fixed doses of 8, 12, 18, or 24 mg or open-label enoxaparin sodium, 30 mg, subcutaneously twice daily, starting 12 to 24 hours after surgery and continuing for 6 to 12 days. We measured the 6- to 12-day cumulative incidence of symptomatic or venographic deep vein thrombosis, symptomatic pulmonary embolism, and bleeding. RESULTS: A total of 594 patients received at least 1 dose of the study drug; 443 patients were evaluable for efficacy. Rates of overall venous thromboembolism (and proximal deep vein thrombosis or pulmonary embolism) for the 8-, 12-, 18-, and 24-mg doses of ximelagatran were 27% (6.6%), 19.8% (2.0%), 28.7% (5.8%), and 15.8% (3.2%), respectively. Rates of overall venous thromboembolism (22.7%) and proximal deep vein thrombosis or pulmonary embolism (3.1%) for enoxaparin did not differ significantly compared with 24-mg ximelagatran (overall difference, -6.9%; 95% confidence interval, -18.0% to 4.2%; P=.3). There was no major bleeding with administration of 24 mg of ximelagatran twice daily. CONCLUSION: Fixed-dose, unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be safe and effective oral prophylaxis against venous thromboembolism after total knee replacement.

Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study.

BACKGROUND: Prophylaxis is recommended following total joint replacement because of the high risk of venous thromboembolism (VTE). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected deep vein thrombosis (DVT) to about 10-15% in total hip replacement (THR) patients. Ximelagatran is a novel, oral direct thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. We compared the efficacy and safety of ximelagatran with those of enoxaparin for the prevention of VTE in patients undergoing THR. METHODS: This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. Patients received fixed-dose oral ximelagatran 24 mg bid or subcutaneous enoxaparin 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of VTE (by postoperative day 12) included thrombosis determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven DVT or pulmonary embolism (PE). VTE and bleeding events were interpreted by an independent central adjudication committee for primary analysis. RESULTS: Of the 1838 patients randomized, 1557 had either adequate venography or symptomatic, proven VTE (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total VTE were 7.9% (62 of 782 patients) in the ximelagatran group and 4.6% (36 of 775 patients) in the enoxaparin group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal DVT and/or PE occurred in 3.6% (28 of 782 patients) in the ximelagatran group and 1.2% (nine of 774 patients) in the enoxaparin group. Major bleeding events were observed in 0.8% (seven of 906) of the ximelagatran-treated patients and in 0.9% (eight of 910) of the enoxaparin-treated patients (P > 0.95). Non-inferiority of ximelagatran 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the enoxaparin regimen. CONCLUSIONS: Both ximelagatran and enoxaparin decreased the overall rate of VTE compared with that reported historically. However, in this study, enoxaparin 30 mg bid was more effective than ximelagatran 24 mg bid for prevention of VTE in THR. Oral ximelagatran was used without coagulation monitoring, was well tolerated, and had bleeding rates comparable to those of enoxaparin. Further refinement by testing a higher dose of ximelagatran in the patients undergoing THR is warranted.

Patient-controlled analgesia compared with intramuscular injection of analgesics for the management of pain after an orthopaedic procedure.

Patients who were scheduled for an elective joint replacement or spinal procedure were randomly assigned prospectively to one of two groups for the management of postoperative pain: ninety-one patients (Group I) controlled the administration of a narcotic analgesic themselves and ninety-three patients (Group II) received intramuscular injections of a narcotic analgesic, as needed. The patients who controlled the analgesic used a smaller amount of the analgesic on the first postoperative day, but the over-all amount was not significantly different between the two groups. The group that received intramuscular injections reported less pain overall, according to one of three pain-assessment scales, and had more relief of pain over-all and on the first postoperative day, according to another scale. The patients who had had a total joint replacement and who controlled the analgesia walked farther on the first postoperative day than those who received intramuscular injections. There were no significant differences between the two groups with regard to the rate of complications, the arterial oxygen saturation levels during the first twenty-four hours after the operation, or the length of stay in the hospital. The nursing staff preferred the patient-administered method of analgesia, as it necessitated equal or less nursing time to assemble, initiate, and maintain than traditional intramuscular injections. The average cost per patient was $58.58 for the patient-administered analgesia and $22.45 for the intramuscular injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Core decompression of the femoral head for osteonecrosis.

The results of forty core-decompression procedures that were performed for ischemic necrosis of the femoral head in thirty-one patients over a four-year period were retrospectively reviewed to ascertain the effectiveness of the procedure. The data did not support the published rates of success of the procedure for Stage-1 and Stage-2 lesions. With a mean length of follow-up of eighteen months, 60 per cent of the hips that had a decompression prior to collapse of the femoral head demonstrated progression of the lesion and were judged to be a failure by clinical or radiographic criteria. Computerized tomographic scans and magnetic resonance imaging proved to be 100 per cent sensitive for diagnosis in preoperative testing; isotopic bone-scanning was less sensitive (80 per cent). Functional intraoperative testing by the method of Ficat did not provide added sensitivity or specificity to the results of the preoperative bone scan. A postoperative or intraoperative fracture occurred in four hips, for an incidence that exceeded any in previously published reports. We concluded that core decompression should be considered a relatively ineffective procedure with significant morbidity.

The femoral component in total hip arthroplasty. Six to eight-year follow-up of one hundred consecutive patients after use of a third-generation cementing technique.

One hundred consecutive patients had a primary unilateral total hip arthroplasty with use of a single design of the femoral component (Harris Precoat), inserted with a so-called third-generation cementing technique, between July 1985 and June 1987. There were seventy-four women and twenty-six men. The mean age at the time of the operation was seventy-one years (range, forty-one to ninety-two years) and the mean weight was seventy kilograms (range, forty-eight to 105 kilograms). Eleven of the 100 patients died during the follow-up period, all with the implant in place. Of the eighty-nine surviving patients, one had a revision arthroplasty for aseptic loosening. The mean duration of clinical follow-up for the remaining eighty-eight patients was seven years (range, six to eight years). The mean Harris hip score at the latest follow-up evaluation was 91 points (range, 68 to 97 points). Of the eighty-eight patients, eighty-five (97 percent) had a good or excellent result. Radiographic follow-up was performed for eighty-one patients; none had evidence of loosening of the stem, and five (6 percent) had endosteal cavitation but were asymptomatic. The rate of failure (loosening or revision) of the femoral component in the entire series was 1 per cent (one hip). The low rate of failure and the maintenance of good and excellent clinical and radiographic results during this period of follow-up are consistent with reports from other institutions. This strengthens the argument to retain or widen the existing indications for the insertion of a femoral stem with cement in primary total hip arthroplasty.

The effect of the orientation of the acetabular and femoral components on the range of motion of the hip at different head-neck ratios.

BACKGROUND: Prosthetic impingement due to poor positioning can limit the range of motion of the hip after total hip arthroplasty. In this study, a computer model was used to determine the effects of the positions of the acetabular and femoral components and of varying head-neck ratios on impingement and range of motion. METHODS: A three-dimensional generic hip prosthesis with a hemispherical cup, a neck diameter of 12.25 millimeters, and a head size ranging from twenty-two to thirty-two millimeters was simulated on a computer. The maximum range of motion of the hip was measured, before the neck impinged on the liner of the cup, for acetabular abduction angles ranging from 35 to 55 degrees and acetabular and femoral anteversion ranging from 0 to 30 degrees. Stability of the hip was estimated as the maximum possible flexion coupled with 10 degrees of adduction and 10 degrees of internal rotation and also as the maximum possible extension coupled with 10 degrees of external rotation. The effects of prosthetic orientation on activities of daily living were analyzed as well. RESULTS: Acetabular abduction angles of less than 45 degrees decreased flexion and abduction of the hip, whereas higher angles decreased adduction and rotation. Femoral and acetabular anteversion increased flexion but decreased extension. Acetabular abduction angles of between 45 and 55 degrees permitted a better overall range of motion and stability when combined with appropriate acetabular and femoral anteversion. Lower head-neck ratios decreased the range of motion that was possible without prosthetic impingement. The addition of a modular sleeve that increased the diameter of the femoral neck by two millimeters decreased the range of motion by 1.5 to 8.5 degrees, depending on the direction of motion that was studied. CONCLUSIONS: There is a complex interplay between the angles of orientation of the femoral and acetabular components. Acetabular abduction angles between 45 and 55 degrees, when combined with appropriate acetabular and femoral anteversion, resulted in a maximum overall range of motion and stability with respect to prosthetic impingement. CLINICAL RELEVANCE: During total hip arthroplasty, acetabular abduction is often constrained by available bone coverage, while femoral anteversion may be dictated by the geometry of the femoral shaft. For each combination of acetabular abduction and femoral anteversion, there is an optimum range of acetabular anteversion that allows the potential for a maximum range of motion without prosthetic impingement after total hip arthroplasty. These data can be used intraoperatively to determine optimum position.

The clinical course of distal deep venous thrombosis after total hip and total knee arthroplasty, as determined with duplex ultrasonography.

Duplex ultrasonography was used to screen 273 consecutive patients, on the fourth day after a total hip or total knee arthroplasty, for the presence of a distal deep venous thrombosis. Patients who had a history of thromboembolic disease or who had an active neoplasm were excluded from the study. Of the 273 patients, twenty-four (9 per cent) were found to have a proximal deep venous thrombosis (a thrombosis involving the femoral or popliteal veins) and forty-one (15 per cent), a distal deep venous thrombosis (a thrombosis involving the veins of the calf). All of the thromboses were asymptomatic. The forty-one patients in whom a distal deep venous thrombosis had been detected with duplex screening subsequently had serial duplex examinations, on the seventh and fourteenth postoperative days. If a proximal deep venous thrombosis was detected, anticoagulation was begun immediately. If no proximal thrombosis was observed, the distal thrombosis was considered stable, the serial duplex examinations were terminated, and clinical observation was continued. Of the forty-one patients who had serial examinations, seven (17 per cent) had a proximal deep venous thrombosis in the ipsilateral limb by the fourteenth postoperative day; all seven were asymptomatic, and all were managed with anticoagulation. Thirty-four patients (83 per cent) were determined to have a stable distal deep venous thrombosis on the fourteenth postoperative day, and no additional duplex examinations were performed. Thirty-three (97 per cent) of these thirty-four patients remained asymptomatic for deep venous thrombosis thereafter; the remaining patient (3 per cent) had a proximal deep venous thrombosis in the ipsilateral limb eleven months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyethylene wear after total hip arthroplasty: the effect of a modular femoral head with an extended flange-reinforced neck.

The use of modular components in total hip arthroplasty has been thought to contribute to accelerated polyethylene wear. Specifically, a modular femoral head with a flange extension and a longer neck may cause increased wear. The purpose of the current study was to evaluate the effect of a flange extension on polyethylene wear. Ninety-one patients who had had a total of 100 primary total hip arthroplasties were evaluated after an intermediate duration of follow-up. All of the acetabular components consisted of a hemispherical titanium-alloy fiber-mesh porous-coated shell with a nonelevated modular polyethylene liner; they were inserted without cement and with use of supplemental screws through the dome after so-called line-to-line reaming. All of the femoral components consisted of a modular head with a diameter of twenty-eight millimeters and either a long neck (with a flange extension) or a short or medium neck (without a flange extension). The study group comprised sixty-two patients (sixty-six hips) who had had radiographic evaluation that was adequate to allow the valid measurement of polyethylene wear. Thirty-two hips were in men, and thirty-four were in women. The mean age of the patients was fifty-six years, the mean weight was seventy-three kilograms, and the mean duration of follow-up was 6.1 years (range, four to eight years). The rate of polyethylene wear in the eleven hips in which the femoral component had a flange extension was significantly greater than that in the fifty-five in which the femoral component did not have a flange extension (mean, 0.17 compared with 0.11 millimeter per year; p = 0.009). Multivariate analysis showed that the presence of a flange extension was associated with increased polyethylene wear to a greater degree (F = 2.86) than were all other variables that were measured, including a younger age (F = 1.72), a more vertical angle of the acetabular component (F = 0.49), a heavier weight (F = 0.14), male gender (F = 0.11), and a smaller initial thickness of the polyethylene (F = 0.02). These data support an association between the presence of a modular femoral head with a flange extension and an accelerated rate of polyethylene wear. The presumed mechanism is an increase in peripheral, or so-called rim, impingement of the flange-reinforced neck on the acetabulum due to a decrease in the ratio between the diameters of the femoral head and neck.

Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge.

BACKGROUND: Venous thromboembolic disease in the form of deep venous thrombosis and pulmonary embolism is a major risk after a total hip arthroplasty. Enoxaparin, a low-molecular-weight heparin, has been shown to reduce the prevalence of deep venous thrombosis after total hip arthroplasty. Warfarin, an orally administered anticoagulant, has been used historically to reduce the risk of deep venous thrombosis after total hip arthroplasty. METHODS: We compared enoxaparin and adjusted-dose warfarin with respect to their safety and their efficacy in the prevention of clinically important venous thromboembolic disease, defined as distal or proximal deep venous thrombosis or pulmonary embolism, or both, during hospitalization after total hip arthroplasty. We also evaluated the prevalence of complications and mortality from venous thromboembolic disease within three months after discharge. RESULTS: Three thousand and eleven patients at 156 centers were randomly assigned to prophylactic treatment with injection of enoxaparin or oral administration of adjusted-dose warfarin during hospitalization. During the study, fifty-five (3.6 percent) of the 1516 patients who were managed with enoxaparin and fifty-six (3.7 percent) of the 1495 patients who were managed with warfarin had venous thromboembolic disease. Twenty-one patients (0.7 percent), which included four (0.3 percent) of those managed with enoxaparin and seventeen (1.1 percent) of those managed with warfarin (p = 0.0083), had venous thromboembolic disease during hospitalization. After discharge from the hospital, venous thromboembolic disease developed in ninety patients (3.0 percent): fifty-one (3.4 percent) of those managed with enoxaparin and thirty-nine (2.6 percent) of those managed with warfarin. One patient who had been managed with enoxaparin died because of a pulmonary embolism, which was confirmed at autopsy. Three additional patients (one who had been managed with enoxaparin and two who had been managed with warfarin) died, and the deaths were attributed to venous thromboembolic disease; however, no autopsies were performed. Twenty-six patients (0.9 percent) (eighteen managed with enoxaparin and eight managed with warfarin) had clinically important bleeding. CONCLUSIONS: Inpatient programs providing treatment with either enoxaparin (thirty milligrams every twelve hours) or adjusted-dose warfarin for a mean of 7.3 days afforded protection against venous thromboembolic disease, with overall rates of morbidity and mortality of 3.7 and 0.6 percent, respectively, and a very low rate of major bleeding complications (0.9 percent) for three months after total hip arthroplasty. During hospitalization, the patients managed with enoxaparin had a lower rate of venous thromboembolic disease than those managed with adjusted-dose warfarin (p = 0.0083). This benefit was lost after the medication was discontinued, with no difference in the prevalences of venous thromboembolic disease between the two groups at three months after discharge from the hospital.

Postoperative surveillance for deep venous thrombosis with duplex ultrasonography after total knee arthroplasty.

Duplex ultrasonography of the lower extremity was used for routine non-invasive screening for asymptomatic proximal and distal deep venous thrombosis, for monitoring of potential propagation of deep venous thrombosis from distal to proximal, and for confirmation of the resolution of proximal deep venous thrombosis after treatment. In the first part of the study, to substantiate the accuracy of duplex ultrasonography, 130 lower limbs (seventy-nine patients) were studied with that modality as well as with venography after a total hip or total knee arthroplasty. Compared with venography, duplex ultrasonography demonstrated 100 per cent sensitivity, specificity, and accuracy for the detection of proximal deep venous thrombosis and 88 per cent sensitivity, 98 per cent specificity, and 98 per cent accuracy for the detection of distal deep venous thrombosis. In the second part of the study, 100 patients who had had a total knee arthroplasty and had been managed with pneumatic stockings and aspirin for prophylaxis against deep venous thrombosis had screening of both lower extremities with duplex ultrasonography on the fourth postoperative day. Duplex ultrasonography demonstrated proximal deep venous thrombosis in seven patients and distal deep venous thrombosis in twenty-two patients; all twenty-nine patients were asymptomatic. The patients who had distal deep venous thrombosis had surveillance with serial duplex ultrasonography on the seventh and fourteenth postoperative days; five of these patients were found to have had propagation of the thrombosis to the proximal deep veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group.

A randomized, parallel-group, open-label clinical trial (the physicians, patients, and staff were not blinded with regard to the regimen that had been used) was conducted, between December 1988 and September 1990, to compare the safety and efficacy of enoxaparin, a low-molecular-weight heparin, with the safety and efficacy of unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. Six hundred and ten patients were randomized, and 607 patients received one of the study medications. The evaluations of efficacy included contrast-media venography, non-invasive vascular examination, and clinical examination. Data on efficacy were available for 604 patients, who had been assigned to one of three treatment groups: thirty milligrams of enoxaparin every twelve hours (194 patients), forty milligrams of enoxaparin once daily (203 patients), or 5000 units of unfractionated heparin every eight hours (207 patients). All drugs were administered subcutaneously. Dosages were not adjusted on the basis of the results of coagulation tests or the body weight of the patient. Treatment was initiated within twenty-four hours after the operation and continued for a maximum of seven days. The primary safety outcome was the occurrence of bleeding episodes. An intent-to-treat patient analysis revealed that deep venous thrombosis occurred in nine (5 per cent) of the 194 patients who received thirty milligrams of enoxaparin every twelve hours, thirty (15 per cent) of the 203 patients who received forty milligrams of enoxaparin once daily, and twenty-four (12 per cent) of the 207 patients who received unfractionated heparin. The rate of deep venous thrombosis was significantly lower in the group that received thirty milligrams of enoxaparin every twelve hours than in the group that received unfractionated heparin (p = 0.03) and in the group that received forty milligrams of enoxaparin once daily (p = 0.0002). No clinically symptomatic pulmonary embolism was observed during the treatment or follow-up phase of this study in the group that received thirty milligrams of enoxaparin every twelve hours. Analysis of evaluable patients revealed a marked reduction in the rate of deep venous thrombosis in the group that received thirty milligrams of enoxaparin every twelve hours (eight [6 per cent] of 136 patients) compared with the group that received heparin (twenty-one [15 per cent] of 145 patients) (p = 0.10); however, this difference was not significant because of the small number of patients included in this analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Instrumented implant for measuring tibiofemoral forces.

Experimental measurement of loads occurring in the human knee joint will allow validation of analytical models and provide data for the design of total knee implants. A customized transducer was developed to measure the dynamic tibiofemoral force and center of pressure after total knee arthroplasty. The transducer consists of a standard tibial component to which four uniaxial load cells and an additional tibial tray have been added. The transducer was calibrated using a loading device traceable to the National Institute of Standards and Technology (NIST). The transducer was accurate to within 1% in magnitude, 0.07 mm in medial/lateral location and 0.24 m in anterior/posterior location.

Use of Postoperative TENS and Continuous Passive Motion Following Total Knee Replacement.

This randomized study analyzed the effectiveness of postoperative transcutaneous electrical nerve stimulation (TENS) used continuously for the first three postoperative days following total knee replacement (TKR) for 1) pain relief, 2) knee flexion arc, 3) narcotic dosage, and 4) hospital stay. Group 1 (N = 18) received sensory threshold TENS and group 2 (N = 18) received subthreshold TENS. Both groups also used continuous passive motion during their hospitalization as did patients from group 3 (control, N = 12) that did not receive TENS. Pain decrease from postoperative day 1-3 was 50% for group 1 patients and 38% for group 2 patients, as measured by the visual analog scale. Wilcoxon Rank Sum did not show a significant difference (p > 0.05) for pain relief or hospital stay for these two groups. Analysis of variance failed to show significant differences (p > 0.05) for knee flexion arc or narcotic dosage for the three groups. Although not statistically significant, an observed decrease in pain may be the only indication for postoperative TENS after TKR. J Orthop Sports Phys Ther 1990;11(12):599-604.

Surgical reconstruction of acquired spastic foot and ankle deformity.

With the aging population and improved methods of emergency transport, the number of surviving stroke and brain injury patients continues to increase. Aggressive rehabilitation of appropriate candidates is justified. In the period of spontaneous recovery, efforts are made to prevent fixed contractures using passive mobilization, splinting, nerve blocks, and electrical stimulation. If deformity persists and the patient is no longer recovering, operative management can help alleviate the functional and hygiene problems associated with these limb deformities.

A historical review of compartment syndrome and Volkmann's ischemic contracture.

Compartment syndrome has been a recognized disease entity since the mid-nineteenth century. Extensive research and clinical observation have allowed for a better understanding of this uniquely complex disease process. Outstanding contributions by clinicians over the past century have provided the basis for our current perspective on its pathogenesis, diagnosis, and treatment. Although Volkmann's early reference to increased "pressure" as the cause of this syndrome was made over 100 years ago, today's modern concept of treatment to prevent contracture based on increased intracompartment pressure has evolved only through the combined efforts of various committed clinicians during the past century.

Recent advances in the use of low molecular weight heparins as prophylaxis for deep vein thrombosis.

Low molecular weight heparins are providing a new prophylactic option for preventing deep vein thrombosis (DVT) in patients undergoing joint replacement surgery. Fragmentation of heparin in laboratory studies revealed differences in coagulation and bleeding factors. This unexpected finding led to clinical trials, starting in 1985 in Europe and the United States. By late 1993, more than 10,000 patients had been admitted to clinical trials of low molecular weight heparins (LMWH) for prevention of DVT. Results of these trials indicated that LMWHs were more effective than unfractionated heparins or warfarin in preventing DVT with no significant increase in bleeding noted.

Consortium data: comparative efficacy of low molecular weight heparin and warfarin following total hip replacement.

ABSTRACTThe Consortium Study is a prospective, randomized research project designed to extend the medical community's understanding of the incidence of thromboembolic disease following hip replacement surgery. The study's methodology of assessing deep vein thrombosis (DVT) and pulmonary embolism (PE) is by clinical symptomatology. Once clinical symptoms occur, diagnostic confirmation includes noninvasive techniques such as duplex ultrasonography, venography, VQ lung scan, and/or lung angiography. The study is designed to recruit a cohort of 4500 patients and will involve 150 medical centers in the United States. The final conclusion and definitive data of the incidence of DVT and PE, when comparing enoxaparin with warfarin, will be available after the full complement of 4500 patients is recruited. This study will demonstrate the incidence of thromboembolic disease during the acute hospital phase and the medium-term phase for the patient undergoing elective hip replacement.in the health care delivery system that were causing patients to leave the hospital earlier. We didn't know what technology to use for patient surveillance.

Consortium data: comparative efficacy of low molecular weight heparin and warfarin following total hip replacement.

The Consortium Study is a prospective, randomized research project designed to extend the medical community's understanding of the incidence of thromboembolic disease following hip replacement surgery. The study's methodology of assessing deep vein thrombosis (DVT) and pulmonary embolism (PE) is by clinical symptomatology. Once clinical symptoms occur, diagnostic confirmation includes noninvasive techniques such as duplex ultrasonography, venography, VQ lung scan, and/or lung angiography. The study is designed to recruit a cohort of 4500 patients and will involve 150 medical centers in the United States. The final conclusion and definitive data of the incidence of DVT and PE, when comparing enoxaparin with warfarin, will be available after the full complement of 4500 patients is recruited. This study will demonstrate the incidence of thromboembolic disease during the acute hospital phase and the medium-term phase for the patient undergoing elective hip replacement.

Indomethacin versus radiation therapy for heterotopic ossification after hip arthroplasty.

This study compared the efficacy and cost of radiation therapy with indomethacin in the prophylaxis of heterotopic ossification following total hip replacement. Twenty-two patients received a radiation dose of 10 Gy in five fractions, 28 patients 8 Gy in one fraction, and 27 patients 25 mg oral indomethacin three times a day for either 7 or 21 days. Patients at higher risk for heterotopic ossification were more likely to receive radiation therapy than indomethacin. At a mean follow-up of 2 years, there were no differences in failure rates between the high-risk patients treated with radiation and the low-risk patients treated with indomethacin. Currently, the patient-billed cost of radiation is $1400 whereas the cost for indomethacin is approximately $100. Indomethacin appears to be as effective as radiation therapy in patients at low to moderate risk for heterotopic ossification and offers significant cost savings.