Infliximab improves vascular stiffness in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. Tumour necrosis factor alpha (TNFalpha)-blocking therapy has been shown to reduce RA disease activity measures and joint damage progression. Some observational studies suggest that TNFalpha blockade reduces mortality and incidence of first cardiovascular events. The mechanisms contributing to these outcomes are unclear. This study assessed the effects of infliximab treatment on vascular stiffness and structure in patients with RA. METHODS: A post hoc analysis of longitudinal data from a randomised placebo controlled study evaluated the effect of infliximab on vascular assessments. 26 patients received intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter to week 54. Patients were followed up to 56 weeks of infliximab therapy with assessments of RA disease activity, cardiovascular risk factors, vascular stiffness (pulse wave velocity (PWV)), carotid intima media thickness (CIMT) and carotid artery plaque (CAP). Univariate analyses of changes over time by repeated measures analysis of variance (ANOVA) were followed by multivariate time-series regression analysis (TSRA) if changes were seen. RESULTS: PWV was significantly lower (better) after 56 weeks of treatment with infliximab (ANOVA p<0.01, TSRA p<0.01). However, CIMT (ANOVA p = 0.50) and CAP (chi(2) = 4.13, p = 0.88) did not change over the study period. Multiple cardiovascular risk measures did not change with treatment and did not correlate with changes in measures of vascular structure. CONCLUSIONS: Arterial stiffness improves with infliximab treatment in RA. This change may help explain the improved cardiovascular disease survival in patients with RA receiving TNFalpha-blocking therapy.

Arthroscopic estimation of the extent of chondropathy.

INTRODUCTION: Arthroscopy has been used to evaluate articular cartilage (AC) pathology in osteoarthritis (OA) for outcome measurement and validation of non-invasive imaging. However, many fundamental aspects of arthroscopic assessment remain un-validated. OBJECTIVES: This study evaluated arthroscopic estimates of extent of chondropathy. METHODS: Serial arthroscopic assessments were performed in a group of 15 sheep before and after bilateral stifle medial meniscectomy (MMx). Post-mortem assessments were performed in un-MMx sheep and 4 and 16 weeks post-MMx. Arthroscopic assessments of the extent of each grade of chondropathy were compared with a non-arthroscopic hybrid assessment that incorporated biomechanical, thickness and macroscopic assessments. RESULTS: Arthroscopy evaluated only 36% of AC and missed significant pathological changes, softening and chondro-osteophyte, occurring in peripheral regions. The patterns of change in arthroscopic assessments were similar to those of the non-arthroscopic assessment but there was a very strong tendency to over-estimate the extent of softened AC after MMx. In spite of these limitations arthroscopic assessments were responsive to change. Estimates of the extent of normal and softened AC were most responsive to change over time followed by estimates of superficial and deep fibrillation. Arthroscopy was as an excellent discriminator between normal and OA. Assessments of chondro-osteophyte and exposed bone were not responsive to change. CONCLUSIONS: Arthroscopic estimates of extent of chondropathy are prone to substantial error. While experience and training may reduce these errors other approaches may more effectively improve performance.

Arthroscopy -- a potential "gold standard" for the diagnosis of the chondropathy of early osteoarthritis.

OBJECTIVES: The aims of this study were to: 1. Evaluate the performance of arthroscopy for the diagnosis of chondropathy and to compare it to that of direct non-arthroscopic assessments; 2. Determine intra-observer reliability of arthroscopic assessments; 3. Evaluate the effects of the arthroscopic video quality and probing upon diagnostic performance. DESIGN: The ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) was used assuming that pre-MMx articular cartilage (AC) was "normal" and post-MMx AC "chondropathic". Video recordings of arthroscopic assessments of each stifle compartment were evaluated. Scores were given for the quality of the video and the amount of probing. The diagnostic performances of dynamic shear modulus (G), light microscopic assessment and superficial zone collagen birefringence assessments were evaluated and compared to that of arthroscopy. Intra-observer reliability of arthroscopic assessments was also evaluated. RESULTS: Arthroscopic assessments had high sensitivity (91-100%), specificity (62-88%) and accuracy (75-93%) for the diagnosis of chondropathy 16 weeks after MMx. Arthroscopy compared favourably with the direct non-arthroscopic assessments in the lateral compartment and was found to have extremely high intra-observer reliability (kappa 0.78-1.00). The quality of arthroscopic video recordings and the amount of probing did not significantly influence accuracy or reliability. CONCLUSIONS: Arthroscopy performs as well as direct non-arthroscopic assessments of AC for diagnosis of early OA. These results suggest that arthroscopy can be used as a "gold standard" for the validation of non-invasive assessments like magnetic resonance imaging and that arthroscopic diagnosis can be based on small amounts of video footage without AC probing.

Biomechanical, histologic and macroscopic assessment of articular cartilage in a sheep model of osteoarthritis.

OBJECTIVES: Our primary objective was to explore the full potential of the ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) for studies to validate non-destructive articular cartilage (AC) assessments and therapeutic interventions. Our secondary objective was to re-evaluate the relationships between the different types of AC assessment after MMx in sheep. METHODS: Macroscopic assessments, dynamic shear modulus (G*), phase lag and AC thickness measurements were performed at a total of 5437 reference points on all six articular surfaces in four normal joints and 16 MMx ovine stifle (knee) joints. Comparisons with histologic assessments of gross structural damage, collagen organisation (birefringence) and proteoglycan content were possible at 702 of these points. RESULTS: Histologic gross structural damage and proteoglycan loss were seen throughout the joint with greatest severity (fibrillation) in closest proximity to the MMx site. Increases in AC (30-50%) thickness, reductions in G* (30-40%) and collagen birefringence intensity (15-30%) occurred more evenly throughout the joint. Macroscopic softening was evident only when G* declined by 80%. G* correlated with AC thickness (rho=-0.47), collagen organisation rho=0.44), gross structural damage (rho=-0.44) and proteoglycan content (rho=0.42). Multivariate analysis showed that collagen organisation contributed twice as much to dynamic shear modulus (t=6.66 as proteoglycan content (t=3.21). Collagen organisation (rho=0.11) and proteoglycan content (rho=0.09) correlated only weakly to phase lag. CONCLUSIONS: Macroscopic assessments were insensitive to AC softening suggesting that arthroscopic assessments of AC status might also perform poorly. Collagen integrity was more important for the maintenance of AC stiffness (G*) than proteoglycan content. The development of major AC softening and thickening throughout the joint following MMx suggested involvement of non-mechanical (e.g., protein and biochemical) chemical and cytokine mediated processes in addition to the disturbance in biomechanical loading. The ovine MMx model provides a setting in which the spectrum of AC changes associated with the initiation and progression of OA may be evaluated.

Impact of selective cyclooxygenase-2 inhibitors on anti-ulcer medication and non-steroidal anti-inflammatory drug use in patients with rheumatic disease.

BACKGROUND: Anti-inflammatory medications are the most common treatment for rheumatic disease in Australia. Recent years have seen large increases in the use of selective cyclooxygenase-2 (COX-2) inhibitors. Predictors of use, costs and benefits of the new medications have not been evaluated. AIMS: To determine trends in selective COX-2 inhibitor, non-steroidal anti-inflammatory drug (NSAID) and anti-ulcer medication (AUM) prescription following the introduction of selective COX-2 inhibitors; to determine predictors of selective COX-2 inhibitor, NSAID and AUM prescribing and to perform a limited evaluation of the costs and benefits associated with the introduction of selective COX-2 inhibitors. METHODS: Groups of consecutive patients attending a hospital rheumatology clinic, private rooms of consulting rheumatologists and a dermatology outpatient clinic were surveyed by investigator-administered questionnaire on three separate occasions. Information was sought about AUM, NSAID and selective COX-2 use and about factors likely to influence selective COX-2 prescribing. Sampling was carried out at 3, 10 and 16 months after the release of COX-2 selective inhibitors in Australia. The final survey was 3 months after Pharmaceutical Benefits Scheme (PBS) listing of celecoxib in Australia. Costs of treatment were calculated from survey findings of frequency of drug use as well as published drug prices and hospitalisation costs. RESULTS: Four-hundred and fifty-eight patients were surveyed. From the 3 months post-release to the 3 months post-PBS listing, a period of 13 months, COX-2 use in rheumatology patients increased from 18 to 57%. De novo prescription of selective COX-2 inhibitors increased from 42 to 61%. During the same period there was a fall in both NSAID (43-20%) and AUM use (41-27%). Neither selective COX-2 inhibitor nor NSAID prescription was related to risk factors for gastro-intestinal (GI) complications, but AUM use was found to correlate strongly to histories of gastroscopy, GI ulceration or GI bleed. The calculated increase in the cost of treatment was $1 033 002/10 000 patients per year. The net cost per serious GI event prevented was $71 736, compared with the normal cost of treatment of $2004. CONCLUSIONS: Among rheumatology patients, selective COX-2 inhibitors have largely replaced NSAIDs and have resulted in a reduction in AUM consumption, but prescribing patterns for selective COX-2 inhibitors have not been related clearly to risk factors for GI complications. The introduction of selective COX-2 inhibitors has been associated with a significant increase in expenditure.

Poor accuracy and interobserver reliability of knee arthroscopy measurements are improved by the use of variable angle elongated probes.

OBJECTIVES: (a)To determine the accuracy and reliability of arthroscopic measurements of cartilage lesion diameter in an artificial right knee model; (b) to determine whether the use of a set of variable angle elongated probes improves performance; and (c) to identify other sources of variability. METHODS: Ovoid "lesions" were drawn on the five cartilage surfaces of four plastic knees models. Two observers assessed these 20 lesions arthroscopically, measuring two diameters in orientations parallel and orthogonal to the probe. Observer 1 (orthopaedic surgeon) and observer 2 (arthroscopic rheumatologist) made two sets of measurements, firstly with the conventional probe and five months later with the variable angle elongated (VAE) probes. The knees were disarticulated to determine true lesion diameter. RESULTS: Observer 1 had negligible bias and good accuracy regardless of orientation or probe type. Observer 2 demonstrated both bias and poor accuracy using the conventional probe. Both improved using VAE probes. Poor interobserver reliability with conventional probes also improved using VAE probes. Major sources of variability could be traced to the probe type, the characteristics of the operator, and the orientation of the lesion in relation to the probe; the lesion location itself did not cause variability. CONCLUSIONS: Variation in accuracy and poor interobserver reliability of measurements with conventional methods of cartilage lesion diameter measurement improved when specially designed measurement probes were used. Arthroscopic measurements performed as well as most clinical and radiographic measures. These findings have important implications for the use of arthroscopy as an outcome in multicentre trials where arthroscopists have different levels of experience.

Prospective evaluation of magnetic resonance imaging and physical examination findings in patients with greater trochanteric pain syndrome.

OBJECTIVE: This study examined patients with greater trochanteric pain syndrome (GTPS) to determine the prevalence of gluteus medius pathology by utilizing magnetic resonance imaging (MRI), and to evaluate the presence of Trendelenburg's sign, pain on resisted hip abduction, and pain on resisted hip internal rotation as predictors of a gluteus medius tear in this group of patients. METHODS: Twenty-four subjects with clinical features consistent with GTPS were recruited. A standard physical assessment was performed at study entry, including assessment of the 3 specific physical signs. Following this initial assessment, MRI of the affected hip was performed. A 1.5T whole body MRI system was utilized, with T1 and T2 fast spin-echo sequences performed in the coronal and axial planes. All MR images were reviewed in random order by a single radiologist. In 12 patients, the 3 physical signs were assessed at study entry and at 2 months by the same observer and the intraobserver reliability for each of the signs was calculated. RESULTS: All subjects were women (median age 58 years, range 36-75 years). The median duration of symptoms was 12 months (range 12-60 months). MRI findings were as follows: 11 patients (45.8%) had a gluteus medius tear, 15 patients (62.5%) had gluteus medius tendinitis (pure tendinitis in 9 patients and tendinitis with a tear in 6 patients), 2 patients had trochanteric bursal distension, and 1 patient had avascular necrosis of the femoral head. Trendelenburg's sign was the most accurate of the 3 physical signs in predicting a tendon tear, with a sensitivity of 72.7% and a specificity of 76.9%. Moreover, Trendelenburg's sign was the most reliable measure, with a calculated intraobserver kappa of 0.676 (95% confidence interval 0.270-1.08). CONCLUSION: The results support the hypothesis that gluteus medius tendon pathology is important in defining GTPS. In this series, trochanteric bursal distension was uncommon and did not occur in the absence of gluteus medius pathology. The physical findings suggest that Trendelenburg's sign is the most sensitive and specific physical sign for the detection of gluteus medius tears, with an acceptable intraobserver reliability. Further delineation with MRI, especially in patients with a positive Trendelenburg's sign, is recommended prior to any consideration of surgery in this group of patients. Finally, with the pathology of this condition defined, the challenge will be to devise and assess, by randomized controlled trial, an appropriate treatment strategy for this group of patients.

The effects of time course after anterior cruciate ligament injury in correlation with meniscal and cartilage loss.

In this study, 130 consecutive patients with anterior cruciate ligament insufficiency who were undergoing ligament reconstruction underwent arthroscopic examination at the time of reconstruction, and any loss of meniscal or chondral integrity was documented in a systematic fashion. In these patients, a greater proportion of the medial meniscus was lost compared with the lateral meniscus (16% versus 5%). On average, 6 cm2 of the articular cartilage was damaged (5.2 cm2) or lost (0.8 cm2), with the area of damage and loss greatest on the medial femoral condyle. Patients whose injuries had occurred more than 2 years before the examination had more than sixfold greater cartilage loss and damage compared with those whose injuries had occurred within the past 2 months. Meniscal loss was associated with a threefold increase in cartilage damage or loss. The group of patients with meniscal loss whose initial anterior cruciate ligament injury occurred more than 2 years before examination exhibited 18 times the amount of cartilage loss or damage as did the group that had no meniscal loss and whose injury occurred less than 1 month before examination.

Electroconvulsive therapy in old-old patients.

The authors compared falls, cardiovascular factors, confusion, gastrointestinal, pulmonary, and metabolic side effects for "old-old" (>75 years) patient groups treated with either electroconvulsive therapy (ECT) or pharmacotherapy. A subset of a pharmacotherapy patient group was selected to match for age, sex, and diagnosis in a case-control design. Side effects were recorded from each selected patient's medical record and compared between groups. Patients receiving ECT showed fewer cardiovascular and gastrointestinal side effects. Patients receiving ECT had longer lengths of stay and more favorable outcomes. Overall, there was a tendency for ECT to result in fewer side effects and better treatment outcomes. ECT appears to be relatively safe and more effective than pharmacotherapy for major depressive disorders in old-old patients.