Comparison of different rating scales for the use in Delphi studies: different scales lead to different consensus and show different test-retest reliability.

BACKGROUND: Consensus-orientated Delphi studies are increasingly used in various areas of medical research using a variety of different rating scales and criteria for reaching consensus. We explored the influence of using three different rating scales and different consensus criteria on the results for reaching consensus and assessed the test-retest reliability of these scales within a study aimed at identification of global treatment goals for total knee arthroplasty (TKA). METHODS: We conducted a two-stage study consisting of two surveys and consecutively included patients scheduled for TKA from five German hospitals. Patients were asked to rate 19 potential treatment goals on different rating scales (three-point, five-point, nine-point). Surveys were conducted within a 2 week period prior to TKA, order of questions (scales and treatment goals) was randomized. RESULTS: Eighty patients (mean age 68 ± 10 years; 70% females) completed both surveys. Different rating scales (three-point, five-point and nine-point rating scale) lead to different consensus despite moderate to high correlation between rating scales (r = 0.65 to 0.74). Final consensus was highly influenced by the choice of rating scale with 14 (three-point), 6 (five-point), 15 (nine-point) out of 19 treatment goals reaching the pre-defined 75% consensus threshold. The number of goals reaching consensus also highly varied between rating scales for other consensus thresholds. Overall, concordance differed between the three-point (percent agreement [p] = 88.5%, weighted kappa [k] = 0.63), five-point (p = 75.3%, k = 0.47) and nine-point scale (p = 67.8%, k = 0.78). CONCLUSION: This study provides evidence that consensus depends on the rating scale and consensus threshold within one population. The test-retest reliability of the three rating scales investigated differs substantially between individual treatment goals. This variation in reliability can become a potential source of bias in consensus studies. In our setting aimed at capturing patients' treatment goals for TKA, the three-point scale proves to be the most reasonable choice, as its translation into the clinical context is the most straightforward among the scales. Researchers conducting Delphi studies should be aware that final consensus is substantially influenced by the choice of rating scale and consensus criteria.

[Hip Osteoarthritis - Epidemiology and Current Medical Care Situation - Health Care Data of 2.4 Million AOK Baden-Württemberg Insurees Aged 40 Years or Older]. / Koxarthrose ­ Epidemiologie und Versorgungsrealität ­ Versorgungsdatenanalyse von 2,4 Millionen Versicherten der AOK Baden-Württemberg ab 40 Jahren.

BACKGROUND: Due to demographic changes an increasing number of hip osteoarthritis can be expected with corresponding effects on the health care system. Hence, the objectives of our study were to obtain substantiated evidence about current medical care situation of hip osteoarthritis patients including outpatient care situation and hip replacement surgery. PATIENTS AND METHODS: Overall, the medical care data of 2.4 million insurees of the AOK Baden-Württemberg for the years 2007 to 2016 were analyzed. Lower limit of age was 40 years. The data includes outpatient and inpatient healthcare claims. RESULTS: The age standardized prevalence of hip osteoarthritis in adults aged 40 years or older is 6.18% (95% CI: ± 0.09%) among women and 6.02% (95% CI: ± 0.09%) among men. From the age of 75, sex differences become significant. The maximum number of newly diagnosed cases of hip osteoarthritis (women: 1.31%, men: 1.16%) is found in the 80 - 84-year-olds. From the age of 85, 17.4% of all women and 16.5% of all men show a hip osteoarthritis. The maximum number of hip replacement surgery among osteoarthritis patients (women: 5.2%, men: 4.3%) appears in the 75- to 79-year-olds. After the initial diagnosis of a hip osteoarthritis, every eighth (13.0%) AOK insured person receives a hip replacement surgery within the first year and one in four (24.8%) insurees within 8 years. Irrespective of the main diagnosis, numbers of hip replacement surgery did not increase between 2009 and 2016. On average, 300.9 (women) and 275.8 (men) hip replacement surgeries were performed per 100 000 insured years. From the age of 80, hip osteoarthritis drops back as the main diagnosis fur surgery. Consequently, from the age of 85 more than 70% of all hip replacement patients show a femoral fracture as main diagnosis. Only about ¾ of the hip osteoarthritis patients were in outpatient specialist care in the year before surgery, and far less than half of hip osteoarthritis patients received a referral to physiotherapy. CONCLUSION: Osteoarthritis of the hip occurs approximately equally often in women and men up to the age of 75 years. Nevertheless, women underwent surgery more frequently. Overall, the number of hip replacement surgery has not increased in the last eight years. Within the first eight years after initial diagnosis of hip osteoarthritis 24.8% of all patients receive a hip TEP. Hence, the majority of patients is treated conservatively in the first eight years. A direct comparison between incidence and prevalent hip osteoarthritis patients reveals that after many years of therapeutic care in the last 1 - 2 years prior to surgery, both the specialist care as well as the referral to physiotherapy are reduced. A reassessment of conservative treatment options over time seems to be necessary.

Indication Criteria for Total Knee Arthroplasty in Patients with Osteoarthritis - A Multi-perspective Consensus Study.

Background and Objectives Knee osteoarthritis (OA) is a significant public health burden. Rates of total knee arthroplasty (TKA) in OA vary substantially between geographical regions, most likely due to the lack of standardised indication criteria. We set out to define indication criteria for the German healthcare system for TKA in patients with knee OA, on the basis of best evidence and transparent multi-stakeholder consensus. Methods We undertook a complex mixed methods study, including an iterative process of systematic appraisal of existing evidence, Delphi consensus methods and stakeholder conferences. We established a consensus panel representing key German national societies of healthcare providers (orthopaedic surgeons, rheumatologists, pain physicians, psychologists, physiotherapists), payers, and patient representatives. A priori defined consensus criteria were at least 70% agreement and less than 20% disagreement among the consensus panel. Agreement was sought for (1) core indication criteria defined as criteria that must be met to consider TKA in a normal patient with knee OA, (2) additional (not obligatory) indication criteria, (3) absolute contraindication criteria that generally prohibit TKA, and (4) risk factors that do not prohibit TKA, but usually do not lead to a recommendation for TKA. Results The following 5 core indication criteria were agreed within the panel: 1. intermittent (several times per week) or constant knee pain for at least 3 - 6 months; 2. radiological confirmation of structural knee damage (osteoarthritis, osteonecrosis); 3. inadequate response to conservative treatment, including pharmacological and non-pharmacological treatment for at least 3 - 6 months; 4. adverse impact of knee disease on patient's quality of life for at least 3 - 6 months; 5. patient-reported suffering/impairment due to knee disease. Additional indication criteria, contraindication criteria, and risk factors for adverse outcome were also agreed by a large majority within the multi-perspective stakeholder panel. Conclusion The defined indication criteria constitute a prerequisite for appropriate provision of TKA in patients with knee OA in Germany. In eligible patients, shared-decision making should eventually determine if TKA is performed or not. The next important steps are the implementation of the defined indication criteria, and the prospective investigation of predictors of success or failure of TKA in the context of routine care provision in Germany.

Outcome in total knee arthroplasty with a medial-lateral balanced versus unbalanced gap.

PURPOSE: To evaluate the clinical outcome in 108 total knee arthroplasty (TKA) patients with a medial-lateral balanced versus unbalanced gap after a mean follow-up of 34 months. METHODS: 64 women and 44 men (mean age, 69.5 years) underwent computer-assisted TKA for osteoarthritis using a cemented fixed-bearing cruciate-retaining prosthesis. The medial-lateral gap difference (measured with the prosthesis in situ and the patella reduced) was balanced (≤2 mm) in 81 patients and unbalanced (>2 mm) in 27 patients. After a mean follow-up of 34 months, patients were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire for pain, stiffness, and physical function. Scores were normalised to 0% (worst) to 100% (best). RESULTS: The balanced and unbalanced gap groups were comparable in terms of age, severity of osteoarthritis, and proportion of pre- and post-operative mechanical alignment. Compared with the balanced gap group, the unbalanced gap group had a larger medial-lateral extension gap difference (0.75±0.57 vs. 2.02±1.15 mm, p=0.001) and medial-lateral flexion gap difference (0.79±0.63 vs. 2.98±2.13 mm, p=0.001) and lower normalised total WOMAC score (84.9±18 vs. 74.8±20.8, p=0.017). CONCLUSION: WOMAC score is better in TKAs with a medial-lateral balanced (<2 mm) gap.

Are joint line changes after primary navigated total knee arthroplasty predictable?

BACKGROUND: Navigation systems have been successful in reducing the outlier of leg alignment after total knee arthroplasty (TKA). Less is known about the restoration of the anatomical joint line with computer-assisted knee replacement. The aim of this study was to determine whether joint line changes <3 or ≥3 mm are predictable with several pre- and intraoperative parameters. METHODS: The study included a total of 180 cases of primary computer-assisted TKA performed using the gap-balancing/tibia-first technique. The final shift of the joint line was calculated using computer verification of proximal tibial and distal femoral cuts. In consideration of the clinical relevance of a 3-mm joint line shift, patients were stratified into two groups: Group I, with joint line change <3 mm, and Group II, with joint line change ≥3 mm. Between groups, variables such as demographics, Kellgren & Lawrence degree of osteoarthritis, preoperative flexion contracture, pre-/intraoperative mechanical leg alignment, flexion/extension gaps, and implant design/sizes were compared statistically. RESULTS: The absolute joint line shift averaged 1.6 ± 1.3 mm (range 0-6 mm). A joint line shift ≥3 mm was observed in 28 cases (15 %). A statistically significant difference between groups was not identified for any of the parameters. Shift of the joint line did not correlate with the analyzed variables. CONCLUSIONS: Joint line was adequately restored when computer navigation was carefully applied as a measuring tool for primary TKA. Knee joint deformity, leg alignment, gap balance, and implant type did not aid in predicting the joint line shift.

Fibula head is a useful landmark to predict the location of posterior cruciate ligament footprint prior to total knee arthroplasty.

PURPOSE: The hypothesis of our study is that a routine tibial cut during cruciate retaining TKA may result in a partial or a total removal of the PCL footprint. Therefore providing a reliable landmark is essential to estimate the probability of PCL damage with a tibial cut and to enable the surgeon to decide pre-operatively whether a cruciate retaining implant design is suitable. METHODS: In a case series of 175 cruciate retaining TKA, the routinely made standing postoperative AP-view radiographs were evaluated to determine the distance between fibula head and tibial cutting plane. In a second case series knee MRI of 223 subjects were consecutively used to measure the vertical distance between tibial attachment of PCL and fibula head. The probability of partial or total PCL damage was calculated for different vertical distances between tibial cut and fibula head. RESULTS: The vertical distance between the tibial cut and the most proximal point of the fibula head averaged 6.1 mm ±4.8 mm. The mean vertical distance from fibula head to proximal and to distal PCL footprint revealed to be 11.4 mm ±3.7 mm and 5.4 mm ±2.9 mm, respectively. The location of the insertion was not significantly different between subgroups such as age (<50 or >50 years), gender and side. Based on our results 11 (7%) knees were considered at high risk of an entire PCL removal after implantation of a cruciate retaining TKA design. CONCLUSIONS: Currently available routine tibial preparation techniques result in partial or total posterior cruciate ligament detachment. Fibula head as a landmark aids to predict the PCL location and to estimate its disruption pre- and postoperatively on AP-view radiographs.

Case report: A unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle.

Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL). We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy.

Modified minimally invasive latissimus dorsi transfer in the treatment of massive rotator cuff tears: a two-year follow-up of 26 consecutive patients.

Since its inauguration by Gerber in 1988, the latissimus dorsi transfer has become an established surgical option for non-reconstructable, massive posterosuperior rotator cuff tears. We describe 26 consecutive patients, all of whom underwent a latissimus dorsi transfer using a modified single incision mini-invasive Herzberg transfer. The primary focus of this paper was to compare the applied clinical results of this new technique with the published results of the Gerber technique. Following transfer of the latissimus dorsi to restore external rotation, 26 patients were evaluated. The mean age was 60 +/- 18 years. The patients were examined after surgery at an average of 24 months (range: 12-41). The unweighted Constant score rose from 20 (range: 13-34) to 56 (range: 63-81). The acromiohumeral distance remained statistically unchanged from an initial value of 4.7 mm (1-9 mm) to a postoperative value of 4.8 (2-11 mm). In the Hamada classification the level of rotator cuff defect arthropathy increased from 1.7 (1-3) to 1.8 (1-3). On the basis of its low morbidity rate, the latissimus dorsi transfer in Herzberg's modified technique is a sensible alternative to the technique initially described by Gerber, especially when the initial situation exhibits pre-existing weakness of the deltoid muscle.

Titin expression in human articular cartilage and cultured chondrocytes: a novel component in articular cartilage biomechanical sensing?

In striated muscle tissues, the giant protein titin acts as a biomechanically active filament system, coupling stress/strain to gene expression. The objective of the study is to show the existence of titin fragments in human articular cartilage, as in diarthodial joints, chondrocytes are also known to sense and respond to stretching. We have surveyed human cultured cartilage collected from adults with osteoarthritis (OA), without OA and from infants with a set of titin antibodies and primer pairs. Three different antibodies were used for immunolabelling, reacting with titin's N-terminal Z1-Z2 domains, its Novex III exon, and with its PEVK region. An antibody directed to a titin ligand was included, since in cardiac muscle, this has been shown to participate in the transmission of stretch dependent titin-based signals. Our results indicate that although at low levels, titin is expressed in cartilage. Primer pairs detected titin transcripts in cartilage, and consistent with this, antibodies directed to titin's Z-disc region and to its elastic region stained cartilage. Moreover, we also could detect transcription of the titin ligand CARP. Components of the stretch dependent signal machinery in muscle are also expressed in cartilage. Further studies are warranted to address if common stress/strain dependent signalling are conserved in muscle and cartilage tissues.

[The influence of different surface treatments on the primary stability of cementless acetabular cups: an in vitro study]. / Der Einfluss von Oberflächenmerkmalen auf die Primärstabilität einer zementfreien Hüftpfanne: eine mechanische In-vitro-Untersuchung.

INTRODUCTION: Long-term stability of cementless acetabular cups depends on osseointegration, which requires primary stability of the implant. The aim of this study was to determine the influence of different surface treatments on the primary stability of press-fit acetabular cups. Mechanical lever-out tests were performed to quantify the stability in vitro. MATERIALS AND METHODS: A hemispherical press-fit cup design with a flattened pole was used and different surface modifications were applied: smooth, corundum-blasted, titanium plasma spray, rough titan plasma spray, and titanium plasma spray with a rim. The outer diameter of all cups was kept constant. Polyurethane foam was selected as the test material and cup insertion was performed with a maximal force of 6000 N. The excess length between the cup and the surface of the foam blocks was measured. The maximum lever-out force was measured and the lever-out torque was calculated. RESULTS: The excess length of cups with a smooth surface was significantly less (p<0.001) than for the other cups, with no significant differences among the other surface modifications. The lever-out torque for cups with a smooth surface was significantly less (p<0.001) than for the other cups, with no significant differences among the other surface modifications. CONCLUSION: Only the cup with a smooth surface showed significant differences for excess length and lever-out torque. The other surface modifications exhibited the same stability. As long as a rough surface is chosen, cup design seems to have a greater influence on stability than surface modification. Although the study did not mimic real in vivo conditions and the lever-out-torques cannot be transferred to clinical situations, initial stability before bony ingrowth occurred could be clearly analysed.

Metabolic activity and gene expression of osteoarthritic chondrocytes in correlation with radiological and histological characteristics.

The aim of this study was to analyze metabolic activity of osteoarthritic chondrocytes in correlation with radiographic, histologic and gene expression data. Six patients with osteoarthritis (OA) of the knee were analyzed clinically and radiographically (Kellgren and Lawrence, K&L). During total knee replacement surgery cartilage samples from the medial and lateral condyles and tibial plateaus were separately harvested. Specimen were analyzed histologically (Mankin Score) and total RNA was extracted. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR. In order to estimate metabolic activity chondrocytes were cultured in alginate beads and proteoglycan content was measured after 1 week. PG content in cultures was dependent from degradation status of cartilage (medial compartments 20.4 +/- 0.83 ng/ng, lateral compartments 29.9 +/- 3.0 ng/ng P < 0.01). We found a positive correlation of PG content in cultures with Mankin's grading (r = 0.79; P < 0.01) and with K&L scoring (r = 0.57; P = 0.05). There was a considerable variation of expression levels of MMP-3 and AGG. PG metabolism of cultured chondrocytes correlated only with the macroscopic and microscopic degradation status of cartilage. Gene expression showed a high variability and no correlation to PG metabolism indicating a more complex regulation.

Acupuncture and knee osteoarthritis: a three-armed randomized trial.

BACKGROUND: Despite the popularity of acupuncture, evidence of its efficacy for reducing pain remains equivocal. OBJECTIVE: To assess the efficacy and safety of traditional Chinese acupuncture (TCA) compared with sham acupuncture (needling at defined nonacupuncture points) and conservative therapy in patients with chronic pain due to osteoarthritis of the knee. DESIGN: Randomized, controlled trial. SETTING: 315 primary care practices staffed by 320 practitioners with at least 2 years' experience in acupuncture. PATIENTS: 1007 patients who had had chronic pain for at least 6 months due to osteoarthritis of the knee (American College of Rheumatology [ACR] criteria and Kellgren-Lawrence score of 2 or 3). INTERVENTIONS: Up to 6 physiotherapy sessions and as-needed anti-inflammatory drugs plus 10 sessions of TCA, 10 sessions of sham acupuncture, or 10 physician visits within 6 weeks. Patients could request up to 5 additional sessions or visits if the initial treatment was viewed as being partially successful. MEASUREMENTS: Success rate, as defined by at least 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 26 weeks. Additional end points were WOMAC score and global patient assessment. RESULTS: Success rates were 53.1% for TCA, 51.0% for sham acupuncture, and 29.1% for conservative therapy. Acupuncture groups had higher success rates than conservative therapy groups (relative risk for TCA compared with conservative therapy, 1.75 [95% CI, 1.43 to 2.13]; relative risk for sham acupuncture compared with conservative therapy, 1.73 [CI, 1.42 to 2.11]). There was no difference between TCA and sham acupuncture (relative risk, 1.01 [CI, 0.87 to 1.17]). LIMITATIONS: There was no blinding between acupuncture and traditional therapy and no monitoring of acupuncture compliance with study protocol. In general, practitioner-patient contacts were less intense in the conservative therapy group than in the TCA and sham acupuncture groups. CONCLUSIONS: Compared with physiotherapy and as-needed anti-inflammatory drugs, addition of either TCA or sham acupuncture led to greater improvement in WOMAC score at 26 weeks. No statistically significant difference was observed between TCA and sham acupuncture, suggesting that the observed differences could be due to placebo effects, differences in intensity of provider contact, or a physiologic effect of needling regardless of whether it is done according to TCA principles.

Accuracy of Ein Bild Röntgen Analyse in determining wear in total hip arthroplasty in vitro.

The Ein Bild Röntgen Analyse system is used to radiographically measure femoral head penetration in total hip replacement components. Because determining the accuracy of any wear analysis system is more precise and comparable under in vitro conditions, we used a femoral head migration simulator to assess the accuracy of Ein Bild Röntgen Analyse and determine the effect of magnification factors on accuracy. We used onscreen magnifications of 100% and 200% to measure anteroposterior radiographs, which improved the accuracy of determining femoral head penetration. Improvements averaged 0.056 mm (95% CI +/- 0.013 mm) in the X direction and 0.024 mm (95% CI +/- 0.027 mm) in the Y direction. Femoral head penetration was simulated in 0.25-mm steps from 0-1 mm. Accuracy ranged from 0-0.029 mm (95% CI, 0.035-0.067 mm) for the X direction and from 0.001-0.013 mm (95% CI, 0.046-0.079 mm) for the Y direction. Assuming the worst accuracy combined for the X and Y directions, Ein Bild Röntgen Analyse can accurately detect femoral head penetration greater than 0.128 mm. These results are comparable with reported accuracy values for different systems and suggest that magnification tools should be considered with Ein Bild Röntgen Analyse when measuring wear radiographically.

Today's state of the art in surgical robotics*.

OBJECTIVE: This paper describes the current level of development of robots for surgery. MATERIAL AND METHODS: This paper is based on a literature search in Pubmed, IEEExplore, CiteSeer and the abstract volumes of the MICCAI 2002, 2003 and 2004, CARS 2003 and 2004, CAOS 2003 and 2004, CURAC 2003 and 2004 and MRNV 2004 meetings. RESULTS: Divided into different disciplines (imaging, abdominal and thoracic surgery, ENT, OMS, neurosurgery, orthopaedic surgery, radiosurgery, trauma surgery, urology), 159 robot systems are introduced. Their functionality, deployment, origin and mechanical set-up are described. Additional contacts and internet links are listed. CONCLUSIONS: The systems perform diverse tasks such as milling cavities in bone, harvesting skin, screwing pedicles or irradiating tumors. From a technical perspective the strong specialization of the systems stands out. Most of the systems are being developed in Germany, the United States, Japan or France.

Validation of a diffusion chamber as in vitro system for the analysis of compound diffusibility through cartilage tissue.

The validation of a diffusion chamber comprising a donor and a receptor side separated by a cartilage membrane was undertaken according to the basic principles described by Peng et al. (1998). The study had three targets: first to evaluate the chamber as in vitro system by the examination of the diffusibility of compound through bovine cartilage samples; second the analysis of the affinity of compound (RS-130830) to cartilage; third to test the influence of two pre-incubation periods (one or three nights) of the cartilage samples. The validation of the chamber as in vitro system for the analysis of compound diffusibility and affinity to cartilage was performed using membrane slices of fresh bovine cartilage and a hydroxamic acid derivative (RS-130830) known as matrix metalloproteinase inhibitor (MMPI). The influence of the pre-incubation of cartilage was also examined. Compound concentrations in donor, receptor and membrane were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS). Diffusion could be demonstrated after 6 h and finally 24 h incubation: the compound concentration in the receptor increased from 0 to 35 microM (mean) while it decreased in the donor from 200 to 144 microM (mean). We also found compound in the cartilage membrane (approximately 1.2 nmol (mean)). Pre-incubation of cartilage samples in culture buffer is suitable as a storage procedure, since the results on the donor side only were influenced significantly but not for the receptor and the cartilage affinity. Thus, the system could clearly reflect relevant properties of the tested compound with regard to its diffusibility and affinity to cartilage tissue.

Leg axis after computer-navigated total knee arthroplasty: a prospective randomized trial comparing computer-navigated and manual implantation.

To compare the alignment after computer-navigated total knee arthroplasty, 52 patients were randomly allocated to 2 groups. Twenty-seven patients received a total knee arthroplasty with the aid of a kinematic computer-navigation system, and 25 patients received a total knee arthroplasty with the conventional method. Both groups were well balanced concerning demographic data and preoperative scores. At 3-month follow-up, the mechanical alignment of the leg reached the desired straight axis in more cases with the computer-navigated implantation. This difference was statistically significant. The femoral and tibial mechanical anteroposterior axis and the femoral and tibial sagittal tilt (slope) measured on sagittal x-rays were not significantly improved in this patient group.

Efficacy and safety of acupuncture for chronic pain caused by gonarthrosis: a study protocol of an ongoing multi-centre randomised controlled clinical trial [ISRCTN27450856].

BACKGROUND: Controlled clinical trials produced contradictory results with respect to a specific analgesic effect of acupuncture. There is a lack of large multi-centre acupuncture trials. The German Acupuncture Trial represents the largest multi-centre study of acupuncture in the treatment of chronic pain caused by gonarthrosis up to now. METHODS: 900 patients will be randomised to three treatment arms. One group receives verum acupuncture, the second sham acupuncture, and the third conservative standard therapy. The trial protocol is described with eligibility criteria, detailed information on the treatment definition, blinding, endpoints, safety evaluation, statistical methods, sample size determination, monitoring, legal aspects, and the current status of the trial. DISCUSSION: A critical discussion is given regarding the considerations about standardisation of the acupuncture treatment, the choice of the control group, and the blinding of patients and observers.

Effects of dexamethasone on proteoglycan content and gene expression of IL-1beta-stimulated osteoarthrotic chondrocytes in vitro.

We studied the effects of dexamethasone on proteoglycan (PG) concentration and gene expression in human osteoarthrotic chondrocytes stimulated with IL-1beta. Cartilage samples were taken from 7 patients with osteoarthrosis of the knee and chondrocytes cultivated in alginate beads. Dexamethasone was added in three concentrations (10(-5), 10(-6), 10(-7) M) to IL-1beta (100 pg/nL)-stimulated chondrocytes. PG concentration was estimated by a dimethylmethylene blue assay. To assess cell proliferation, DNA content was measured fluorometrically. Quantitative Lightcycler-PCR was used to estimate the mRNA levels of stromelysin-1 (MMP-3) and aggrecan (AGG). The proliferation rate was unchanged in all treatment groups. IL-1beta increased MMP-3 expression by 44% and inhibited AGG expression by 16%, but PG-concentration was reduced by 7%. The addition of dexamethasone to IL-1beta-stimulated chondrocytes further reduced the PG concentration by 19% at 10(-5) M and by 17% at 10(-7) M. The MMP-3 expression was inhibited between 27-53% and the AGG expression between 30-46% by dexamethasone. In osteoarthrotic chondrocytes, dexamethasone in an appropriate dose range reduced the expression of MMP-3 and AGG at the same time. The resulting decrease in PG concentration should be considered when using intraarticular corticosteroids to treat an osteoarthrotic joint.