Cell-Laden and Cell-Free Matrix-Induced Chondrogenesis versus Microfracture for the Treatment of Articular Cartilage Defects: A Histological and Biomechanical Study in Sheep.

OBJECTIVE: The aim of this study was to evaluate the regenerative potential of cell-laden and cell-free collagen matrices in comparison to microfracture treatment applied to full-thickness chondral defects in an ovine model. METHODS: Animals (n = 30) were randomized into 5 treatment groups, and 7-mm full-cartilage-thickness defects were set at the trochlea and medial condyle of both knee joints and treated as follows: 2 scaffolds in comparison (collagen I/III, Chondro-Gide(®); collagen II, Chondrocell(®)) for covering microfractured defects (autologous matrix-induced chondrogenesis), both scaffolds colonized in vitro with autologous chondrocytes (matrix-associated chondrocyte transplantation), or scaffold-free microfracture technique. One year after surgery, cartilage lesions were biomechanically (indentation test), histologically (O'Driscoll score), and immunohistochemically (collagen type I and II staining) evaluated. RESULTS: All treatment groups of the animal model induced more repair tissue and showed better histological scores and biomechanical properties compared to controls. The average thickness of the repair tissue was significantly greater when a scaffold was used, especially the collagen I/III membrane. However, none of the index procedures surpassed the others from a biomechanical point of view or based on the histological scoring. Collagen type II expression was better in condylar defects compared to the trochlea, especially in those treated with collagen I/III membranes. CONCLUSION: Covering of defects with suitable matrices promotes repair tissue formation and is suggested to be a promising treatment option for cartilage defects. However, it failed to improve the biomechanical and histological properties of regenerated articular cartilage compared to microfracture alone in an ovine model under the given circumstances.

Malignant hemangiopericytoma of the breast: a case report with a review of the literature.

INTRODUCTION: A hemangiopericytoma of the breast is uncommon, and a hemangiopericytoma of the breast is even rarer. Only a few cases of hemangiopericytoma of the breast have been reported in literature. CASE REPORT: Here, we report a case of a 66-year-old woman who presented with a mass in her left breast. The patient had trauma to her left breast 2 years ago with consecutive hematoma. An ultrasound-guided core biopsy indicated a malignant vascular tumor. Its morphology and immunohistochemical marker profile was characteristic for a malignant hemangiopericytoma. Thus, she underwent a mastectomy and an axilla sampling. DISCUSSION: The mammogram and the ultrasound findings of 2004 are presented in relation to those of 2006. Hemangiopericytoma of the breast is infrequent, so that the characteristics of this lesion are discussed in addition to the review of the previous literature on this unusual neoplasm.

Surgery is more cost-effective than splinting for carpal tunnel syndrome in the Netherlands: results of an economic evaluation alongside a randomized controlled trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common disorder, often treated with surgery or wrist splinting. The objective of this economic evaluation alongside a randomized trial was to evaluate the cost-effectiveness of splinting and surgery for patients with CTS. METHODS: Patients at 13 neurological outpatient clinics with clinically and electrophysiologically confirmed idiopathic CTS were randomly allocated to splinting (n = 89) or surgery (n = 87). Clinical outcome measures included number of nights waking up due to symptoms, general improvement, severity of the main complaint, paraesthesia at night and during the day, and utility. The economic evaluation was performed from a societal perspective and involved all relevant costs. RESULTS: There were no differences in costs. The mean total costs per patient were in the surgery group EURO 2,126 compared to EURO 2,111 in the splint group. After 12 months, the success rate in the surgery group (92%) was significantly higher than in the splint group (72%). The acceptability curve showed that at a relatively low ceiling ratio of EURO 2,500 per patient there is a 90% probability that surgery is cost-effective. CONCLUSION: In the Netherlands, surgery is more cost-effective compared with splinting, and recommended as the preferred method of treatment for patients with CTS.

Manual therapy, physical therapy, or continued care by the general practitioner for patients with neck pain: long-term results from a pragmatic randomized clinical trial.

OBJECTIVES: The authors' goals were to compare the effectiveness of manual therapy (MT; mainly spinal mobilization), physical therapy (PT; mainly exercise therapy), and continued care by the general practitioner (GP; analgesics, counseling and education) over a period of 1 year. METHODS: One hundred eighty-three patients suffering for at least 2 weeks from nonspecific neck pain were randomized to receive a 6-week treatment strategy of MT once a week, PT twice a week, or GP care once every 2 weeks. The primary outcome measures were perceived recovery, severity of physical dysfunctioning, pain intensity, and functional disability. RESULTS: The differences between groups considered over 1 year were statistically significant (repeated measurements analyses P<0.001 to P=0.02) for all outcomes but borderline for the Neck Disability Index (P=0.06). Higher improvement scores were observed for MT for all outcomes, followed by PT and GP care. The success rate, based on perceived recovery after 13 weeks, was 72% for MT, which was significantly higher than the success rate for continued GP care (42%, P=0.001) but not significantly higher compared with PT treatment (59%, P=0.16). The difference between PT and GP approached statistical significance (P=0.06). After 1 year the success rates were 75%, 63%, and 56%, respectively, and no longer significantly different. CONCLUSIONS: Short-term results (at 7 weeks) have shown that MT speeded recovery compared with GP care and, to a lesser extent, also compared with PT. In the long-term, GP treatment and PT caught up with MT, and differences between the three treatment groups decreased and lost statistical significance at the 13-week and 52-week follow-up.

Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combined step-down prednisolone, methotrexate, and sulfasalazine with sulfasalazine alone.

OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.

Foreign body reactions in lymph nodes of oncology patients with joint prostheses--light-, electron microscopic and immunohistological investigations.

Foreign body reactions in lymph nodes caused by wear particles from joint prostheses can mimic different lymphadenopathies, including metastatic cancer. The knowledge of these alterations is particularly important for pathologists performing frozen section diagnosis for oncology patients. As recent investigations of pseudocapsules have revealed that most of the wear particles are submicron-sized, transmission electron microscopic investigations were additionally performed. The histological investigation of the pelvic lymph nodes of 22 oncology patients with joint prostheses showed that the bone cement wear prevailed. At least small amounts of polyethylene wear particles were also found in all cases. Metallic wear particles were detected in 90% of the cases. The wear particles induce a macrophage-rich foreign body reaction that can cause an architectural effacement of the lymph nodes. The electron microscopic investigations showed that submicron-sized wear particles prevail. Some of them form conglomerates in size ranges detectable by light microscopy. The immunohistochemical studies showed that the foreign body reactions comprised mature CD163- and PGM1-positive macrophages and few lymphocytes, predominantly T-lymphocytes. The knowledge of the characteristic alterations of regional lymph nodes seems important in order to avoid misinterpretations. Therefore, in particular the detection of intracytoplasmatic wear particles is helpful in this respect.

Economic evaluations and randomized trials in spinal disorders: principles and methods.

STUDY DESIGN: Descriptive methodologic recommendations. OBJECTIVE: To help researchers designing, conducting, and reporting economic evaluations in the field of back and neck pain. SUMMARY OF BACKGROUND DATA: Economic evaluations of both existing and new therapeutic interventions are becoming increasingly important. There is a need to improve the methods of economic evaluations in the field of spinal disorders. MATERIALS AND METHODS: To improve the methods of economic evaluations in the field of spinal disorders, this article describes the various steps in an economic evaluation, using as example a study on the cost-effectiveness of manual therapy, physiotherapy, and usual care provided by the general practitioner for patients with neck pain. RESULTS: An economic evaluation is a study in which two or more interventions are systematically compared with regard to both costs and effects. There are four types of economic evaluations, based on analysis of: (1) cost-effectiveness, (2) cost-utility, (3) cost-minimization, and (4) cost-benefit. The cost-utility analysis is a special case of cost-effectiveness analysis. The first step in all these economic evaluations is to identify the perspective of the study. The choice of the perspective will have consequences for the identification of costs and effects. Secondly, the alternatives that will be compared should be identified. Thirdly, the relevant costs and effects should be identified. Economic evaluations are usually performed from a societal perspective and include consequently direct health care costs, direct nonhealth care costs, and indirect costs. Fourthly, effect data are collected by means of questionnaires or interviews, and relevant cost data with regard to effect measures and health care utilization, work absenteeism, travel expenses, use of over-the-counter medication, and help from family and friends, are collected by means of cost diaries, questionnaires, or (telephone) interviews. Fifthly, real costs are calculated, or the costs are estimated on the basis of real costs, guideline prices, or tariffs. Finally, in the statistical analysis the mean direct, indirect, and total costs of the alternatives are compared, using bootstrapping techniques. Incremental cost-effectiveness ratios are graphically presented on a cost-effectiveness plane and acceptability curves are calculated. CONCLUSION: Economic evaluations require specific methods. These recommendations may be helpful in improving the quality of economic evaluations of new and existing therapeutic interventions in the field of spinal disorders.

Cost effectiveness of interventions for lateral epicondylitis: results from a randomised controlled trial in primary care.

OBJECTIVE: Lateral epicondylitis is a common complaint, with an annual incidence between 1% and 3% in the general population. The Dutch College of General Practitioners in The Netherlands has issued guidelines that recommend a wait-and-see policy. However, these guidelines are not evidence based. DESIGN AND SETTING: This paper presents the results of an economic evaluation in conjunction with a randomised controlled trial to evaluate the effects of three interventions in primary care for patients with lateral epicondylitis. PATIENTS AND INTERVENTIONS: Patients with pain at the lateral side of the elbow were randomised to one of three interventions: a wait-and-see policy, corticosteroid injections or physiotherapy. MAIN OUTCOME MEASURES AND RESULTS: Clinical outcomes included general improvement, pain during the day, elbow disability and QOL. The economic evaluation was conducted from a societal perspective. Direct and indirect costs (in 1999 values) were measured by means of cost diaries over a period of 12 months. Differences in mean costs between groups were evaluated by applying non-parametric bootstrap techniques. The mean total costs per patient for corticosteroid injections were euro430, compared with euro631 for the wait-and-see policy and euro921 for physiotherapy. After 12 months, the success rate in the physiotherapy group (91%) was significantly higher than in the injection group (69%), but only slightly higher than in the wait-and-see group (83%). The differences in costs and effects showed no dominance for any of the three groups. The incremental cost-utility ratios were (approximately): euro7000 per utility gain for the wait-and-see policy versus corticosteroid injections; euro12000 per utility gain for physiotherapy versus corticosteroid injections, and euro34500 for physiotherapy versus the wait-and-see policy. CONCLUSIONS: The results of this economic evaluation provided no reason to update or amend the Dutch guidelines for GPs, which recommend a wait-and-see policy for patients with lateral epicondylitis.

Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.

OBJECTIVE: To evaluate the cost effectiveness of physiotherapy, manual therapy, and care by a general practitioner for patients with neck pain. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 183 patients with neck pain for at least two weeks recruited by 42 general practitioners and randomly allocated to manual therapy (n=60, spinal mobilisation), physiotherapy (n=59, mainly exercise), or general practitioner care (n=64, counselling, education, and drugs). MAIN OUTCOME MEASURES: Clinical outcomes were perceived recovery, intensity of pain, functional disability, and quality of life. Direct and indirect costs were measured by means of cost diaries that were kept by patients for one year. Differences in mean costs between groups, cost effectiveness, and cost utility ratios were evaluated by applying non-parametric bootstrapping techniques. RESULTS: The manual therapy group showed a faster improvement than the physiotherapy group and the general practitioner care group up to 26 weeks, but differences were negligible by follow up at 52 weeks. The total costs of manual therapy (447 euro; 273 pounds sterling; 402 dollars) were around one third of the costs of physiotherapy (1297 euro) and general practitioner care (1379 euro). These differences were significant: P<0.01 for manual therapy versus physiotherapy and manual therapy versus general practitioner care and P=0.55 for general practitioner care versus physiotherapy. The cost effectiveness ratios and the cost utility ratios showed that manual therapy was less costly and more effective than physiotherapy or general practitioner care. CONCLUSIONS: Manual therapy (spinal mobilisation) is more effective and less costly for treating neck pain than physiotherapy or care by a general practitioner.

Corticosteroid injections, physiotherapy, or a wait-and-see policy for lateral epicondylitis: a randomised controlled trial.

BACKGROUND: Lateral epicondylitis is generally treated with corticosteroid injections or physiotherapy. Dutch clinical guidelines recommend a wait-and-see policy. We compared the efficacy of these approaches. METHODS: Patients with lateral epicondylitis of at least 6 weeks' duration were recruited by family doctors. We randomly allocated eligible patients to 6 weeks of treatment with corticosteroid injections, physiotherapy, or a wait-and-see policy. Outcome measures included general improvement, severity of the main complaint, pain, elbow disability, and patient satisfaction. Severity of elbow complaints, grip strength, and pressure pain threshold were assessed by a research physiotherapist who was unaware of treatment allocation. We assessed all outcomes at 3, 6, 12, 26, and 52 weeks. The principal analysis was done on an intention-to-treat basis. FINDINGS: We randomly assigned 185 patients. At 6 weeks, corticosteroid injections were significantly better than all other therapy options for all outcome measures. Success rates were 92% (57) compared with 47% (30) for physiotherapy and 32% (19) for wait-and-see policy. However, recurrence rate in the injection group was high. Long-term differences between injections and physiotherapy were significantly in favour of physiotherapy. Success rates at 52 weeks were 69% (43) for injections, 91% (58) for physiotherapy, and 83% (49) for a wait-and-see policy. Physiotherapy had better results than a wait-and-see policy, but differences were not significant. INTERPRETATION: Patients should be properly informed about the advantages and disadvantages of the treatment options for lateral epicondylitis. The decision to treat with physiotherapy or to adopt a wait-and-see policy might depend on available resources, since the relative gain of physiotherapy is small.