Body mass index is not a clinically meaningful predictor of patient reported outcomes of primary hip replacement surgery: prospective cohort study.

OBJECTIVES: To describe whether body mass index (BMI) is a clinically meaningful predictor of patient reported outcomes following primary total hip replacement (THR) surgery. DESIGN: Combined data from prospective cohort studies. We obtained information from four cohorts of patients receiving primary THR for osteoarthritis: Exeter Primary Outcomes Study (EPOS) (n = 1431); EUROHIP (n = 1327); Elective Orthopaedic Centre (n = 2832); and St. Helier (n = 787). The exposure of interest was pre-operative BMI. Confounding variables included: age, sex, SF-36 mental health, comorbidities, fixed flexion, analgesic use, college education, OA in other joints, expectation of less pain, radiographic K&L grade, ASA grade, years of hip pain. The primary outcome was the Oxford Hip Score (OHS). Regression models describe the association of BMI on outcome adjusting for all confounders. RESULTS: For a 5-unit increase in BMI, the attained 12-month OHS decreases by 0.78 points 95%CI (0.27-1.28), P-value 0.001. Compared to people of normal BMI (20-25), those in the obese class II (BMI 35-40) would have a 12-month OHS that is 2.34 points lower. Although statistically significant this effect is small and not clinically meaningful in contrast to the substantial change in OHS seen across all BMI groupings. In obese class II patients achieved a 22.2 point change in OHS following surgery. CONCLUSIONS: Patients achieved substantial change in OHS after THR across all BMI categories, which greatly outweighs the small difference in attained post-operative score. The findings suggest BMI should not present a barrier to access THR in terms of PROMs.

Pre-operative expectation predicts 12-month post-operative outcome among patients undergoing primary total hip replacement in European orthopaedic centres.

OBJECTIVE: Patients' expectations of surgery may be related to outcomes of joint replacement. The aims of this study were to: (1). Identify patient characteristics associated with pre-operative expectations of total hip replacement (THR); (2). Explore whether pre-operative expectations predict surgical outcomes 12-months post-THR. METHOD: The European collaborative database of cost and practice patterns of THR (EUROHIP) study consists of 1327 consenting patients coming to primary THR for osteoarthritis (OA) across 20 European orthopaedic centres. Ordered logistic regression modelling was used to look at the association between patients pre-operative expectations and baseline characteristics (age, sex, education, American Society of Anaesthesiologists (ASA) status, Kellgren & Lawrence (K&L) grade, body mass index (BMI), medication use, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, EQ5D (EuroQol) score). The Outcome Measures in Rheumatology (OMERACT)/Osteoarthritis Research Society International (OARSI) responder criteria were used to classify patients as improved/not improved 12-months post-THR. Logistic regression modelling was used to explore whether pre-operative expectations predict response to THR. RESULTS: Greater numbers of pre-operative expectations were associated with younger age, women, increasing BMI, and more education. The more pre-operative expectations a patient had, the more likely they were to improve after surgery. Each individual expectation a patient had, was associated with a 34% increase in improvement [95% confidential interval (CI) 1%-78%]. Analyses within dimensions of the WOMAC suggest the association is strongest for stiffness and function. CONCLUSION: There is large variation in patients' pre-operative expectations of THR. Greater numbers of pre-operative expectations were associated with improvement following THR. This appears to be driven more by stiffness and function. These findings have implications for informed patient-clinician decision-making.

Gender inequity in the provision of care for hip disease: population-based cross-sectional study.

OBJECTIVES: To examine gender differences along the care pathway to total hip replacement. METHODS: We conducted a population-based cross-sectional study of 26,046 individuals aged 35 years and over in Avon and Somerset. Participants completed a questionnaire asking about care provision at five milestones on the pathway to total hip replacement. Those reporting hip disease were invited to a clinical examination. We estimated odds ratios (ORs) [95% confidence intervals (CI)] for provision of care to women compared with men. RESULTS: 3169 people reported hip pain, 2018 were invited for clinical examination, and 1405 attended (69.6%). After adjustment for age and disease severity, women were less likely than men to have consulted their general practitioner (OR 0.78, 95%-CI 0.61-1.00), as likely as men to have received drug therapy for hip pain in the previous year (OR 0.96, 95%-CI 0.74-1.24), but less likely to have been referred to specialist care (OR 0.53, 95%-CI 0.40-0.70), to have consulted an orthopaedic surgeon (OR 0.50, 95%-CI 0.32-0.78), or to be on a waiting list for total hip replacement (OR 0.41, 95%-CI 0.20-0.87). Differences remained in the 746 people who had sought care from their general practitioner, and after adjustment for willingness and fitness for surgery. CONCLUSIONS: There are gender inequalities in provision of care for hip disease in England, which are not fully accounted for by gender differences in care seeking and treatment preferences. Differences in referral to specialist care by general practitioners might unwittingly contribute to this inequity. Accurate information about availability, benefits and risks of hip replacement for providers and patients, and continuing education to ensure that clinicians interpret and correct patients' assumptions could help reduce inequalities.

The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials.

OBJECTIVE: To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific Citation Index, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library. METHODS: Randomised placebo controlled trials in OA were included. The placebo effect was defined as the overall change from baseline in the placebo group. It was estimated as the effect size (ES; the standard mean difference between baseline and endpoint) and this was compared with the ES obtained from untreated control. ES for pain was the primary outcome. Statistical pooling was undertaken as appropriate and 95% CIs were used for comparison. Quality of trials was assessed and potential determinants of placebo effect were examined using multiple regression analysis. The partial regression coefficient (beta) was used to present the adjusted size of the association. RESULTS: We identified 198 trials with 193 placebo groups (16 364 patients) and 14 untreated control groups (1167 patients) that met our inclusion criteria. These included a range of therapies (non-pharmacological, pharmacological and surgical treatments). Placebo was effective at relieving pain (ES 0.51, 95% CI 0.46 to 0.55 for the placebo group and 0.03, 95% CI -0.13 to 0.18 for untreated control). Placebo was also effective at improving function and stiffness. The pain-relieving effect increased when the active treatment effect (beta=0.38, p<0.001), baseline pain (0.006, p=0.014) and sample size (0.001, p=0.004) increased, and when placebo was given through injections/needles (0.144, p=0.020). CONCLUSION: Placebo is effective in the treatment of OA, especially for pain, stiffness and self-reported function. The size of this effect is influenced by the strength of the active treatment, the baseline disease severity, the route of delivery and the sample size of the study.

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.

Measurement of cartilage volumes in rheumatoid arthritis using MRI.

MRI is a valuable imaging modality for assessment of the articular cartilage in rheumatoid arthritis (RA) and is potentially of use in monitoring disease progression and response to therapy. In this study, we investigated the sources of error in volume measurements obtained by segmentation of MR images of knee cartilage in patients with RA and followed cartilage volume in a group of RA patients for 12 months. 23 RA patient volunteers were recruited for knee imaging. Six subjects were imaged at baseline only, six were imaged at baseline and again within an hour in the same imaging session, six subjects were imaged at baseline and 7 days, and 17 subjects were imaged at baseline, 4+/-2 months and 12 months. Imaging was performed at 1.0 T using a three-dimensional spoiled gradient-echo sequence with fat-suppression. Manual image segmentation was performed once or twice on the lateral tibial, medial tibial, patellar and femoral compartment by either one or two segmenters. Coefficients of variation (CoV) for repeated volume measurement of total cartilage were 2.2% (same segmenter, same scan), 5.2% (different segmenter, same scan), 4.9% (same segmenter, different scan, same session), and 4.4% (same segmenter, different scan, different session). Over the 12 month duration of the study there was no significant change in total cartilage volume, nor were there significant changes in volume in any individual compartment. This measurement technique is reproducible, but any net change in cartilage volume over 1 year is very small.

Clinical manifestations of human parvovirus B19 in adults.

Human parvovirus B19 has been associated with various clinical effects in a number of uncontrolled reports. To define the usual manifestations of B19 infection in adults and the factors that influence them we present a clinicoepidemiological study of an outbreak of B19 infection centered on a junior school. Four hundred fifty-three of 475 adults in this community were interviewed and blood was obtained for serological diagnosis. Fifty-four cases of recent infection were identified and were HLA typed. Fourteen of the cases were asymptomatic; 32 had an influenzalike illness; 23 a rash; and 26 an acute-onset polyarthropathy that was more common in women and lasted for up to 7 months. HLA-A, -B, and -C antigen frequencies were similar to a local control population and showed no association with symptoms except that HLA-DR1 was absent in those with persistent arthropathy.

Nifedipine in the treatment of Raynaud's syndrome.

Thirteen patients with Raynaud's syndrome (10 idiopathic and three with scleroderma) were treated with nifedipine or placebo in a double blind crossover study. The immediate response to 20 mg nifedipine or placebo and the response to a three week course of treatment (10 mg nifedipine eight hourly) were assessed by Doppler mapping of digital arteries, finger pulse volume recordings, skin temperature measurements, and arterial Doppler waveform analysis. In addition, the number, duration, and severity of vasospastic attacks were noted, together with patient and observer opinion of each treatment, an overall pain score, and patient preference. There was a significant reduction in the number of attacks and in linear analogue score for pain after three weeks of nifedipine. Patient and observer opinion showed a significant preference for nifedipine. The objective tests, however, failed to detect any significant change in either the short or long term. This study supports the use of nifedipine for the relief of symptoms in selected patients with Raynaud's syndrome and implies that it may have a unique mode of action.

Proliferative responses of T-cell lines grown from joint fluids of patients with rheumatoid arthritis and other arthritides.

T-cell lines were established by culturing, in the presence of IL-2, mononuclear cells obtained from synovial fluids (SF) of most (77%) patients with rheumatoid arthritis (RA). By contrast, SF from patients with osteoarthritis and crystal synovitis rarely yielded lines. The cell lines were identified as T-cells because they express the CD3 surface antigen and either CD8 or CD4. The ability of the T-cell lines to react with putative antigens was tested using autologous Epstein-Barr virus transformed B-cells (EBV-B) as antigen presenting cells. IgG failed to stimulate proliferation of any RA patients' T-cell lines while Type II collagen stimulated T-cell lines from one RA patient and from one with osteoarthritis. Some T-cell lines (17/26) took up more tritiated thymidine after three days culture with a mixture of autologous SF and irradiated autologous EBV-B than with either alone. The effect could not be ascribed to a mitogen in the RA SF as the fluids failed to stimulate blood mononuclear cells. We consider that RA SF contain a T-cell growth factor which can only exert its effect through an antigen presenting cell (EBV-B).

Idiopathic destructive arthritis of the shoulder.

IDA of the shoulder is a condition found predominantly in elderly females. Although the shoulder is primarily involved, other joints such as the hip and knee can be affected, and concurrent OA is common at other joint sites. Clinical features include voluminous, often blood-stained effusions, together with features of rotator cuff rupture and restriction of shoulder movement. Laboratory parameters are usually normal and examination of the synovial fluid reveals large amounts of basic calcium phosphate crystals. The synovium is hypertrophied and vascular and shows fibrin deposition. It contains calcified material extracellularly. An acute inflammatory infiltrate is absent. Radiographs demonstrate soft tissue swelling and subchondral sclerosis with marked bony attrition involving the acromioclavicular and glenohumeral joints, as well as the humeral head and neck. Although some aspects of the disease seem distinct, many features are shared with other types of destructive arthritis of the shoulder. The pathogenesis of this disorder is at present obscure, but it is clear that an understanding of the processes involved will provide a vital contribution to our understanding of the response of the joint to insult. With a multidisciplinary approach and adequate communication between interested workers this aim could seen be within our grasp.

Protection from gastrointestinal side-effects by azapropazone by its incorporation into a glucose-sodium acid citrate formulation.

Addition of glucose and sodium citrate to azapropazone, in proportions of 1:1:1 by weight reduced gastric mucosal damage in rats and there was a trend towards reduction in radiolabelled faecal red cell loss in human volunteers compared with that with azapropazone alone. The glucose and citrate did not affect the pharmacokinetics of azapropazone, or its therapeutic efficacy. While no difference was observed in endoscopic injury and in symptomatic gastrointestinal complaints in a multicentre comparison in rheumatic patients, a striking reduction in symptoms was observed in those patients with a history of severe gastrointestinal intolerance to non-steroidal anti-inflammatory drugs.

Enhanced oxidative response of polymorphonuclear leukocytes from synovial fluids of patients with rheumatoid arthritis.

Polymorphonuclear leukocytes (PMN) isolated from the synovial fluid (SF) of patients with rheumatoid arthritis (RA) exhibited an enhanced oxidative response to heat aggregated IgG (Hagg) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) as compared with either autologous or normal blood PMN. Normal blood PMN pretreated with synovial fluid showed a significantly increased response to FMLP which was unaffected by prior dialysis of SF. The degree of enhancement produced varied between SF's and was dependent on the period for which cells were incubated and on the concentration of SF used. In contrast there was no enhancement of the oxidative response when Hagg was used as a stimulus. Indeed, SF produced a dose dependent inhibition of Hagg stimulated superoxide production. These observations suggest that SF's from patients with RA contain factors which both enhance and inhibit the oxidative response of PMN depending on the subsequent stimulus.

Frictional response of articular cartilage containing crystals.

Many joint diseases are associated with the deposition of crystals in articular cartilage. Three main types are commonly found: calcium pyrophosphate, calcium hydroxyapatite and monosodium urate. The effects of these articular crystals on the frictional properties and the surface condition of the articular cartilage were studied. A total of 43 cartilage specimens cut from 19 post-mortem knee joints have been tested in purpose-designed apparatus. The results show that a high friction coefficient and a high level of crystal deposition tend to occur with a worsening of the surface quality of the articular cartilage.

Nephrotoxicity studies on aspirin and diflunisal.

Some of the difficulties encountered in investigations of long-term drug nephrotoxicity are reviewed, and the evidence for acute and chronic renal damage induced by aspirin is discussed. Two studies were carried out to investigate the acute effects of diflunisal on the kidney, and to compare its effects with those of aspirin. Measurements were made before, during and after drug intake, of epithelial cells and lysosomal enzyme (beta-d-n-acetyl glucosaminidase) excretion in urine. Diflunisal caused no change in cell excretion and no increase in enzyme secretion in 6 normal volunteers. In a comparative study against aspirin, two groups of 12 patients being treated for osteoarthrosis were observed over an 8-week period. Enzyme excretion increased in both groups and appeared to be dose related. The increase, however, was relatively greater in the aspirin group. The possible significance of these findings is discussed.

Medial femoral condyle necrosis and chondrocalcinosis--a causal relationship?

The three cases of idiopathic medial femoral condyle necrosis, presenting to this hospital over a five-year period, are reported. All the patients also had chondrocalcinosis in the affected knee at the time of presentation, an association previously not recorded. Only one patient, however, showed evidence of generalised chondrocalcinosis. To date two knees have come to total knee replacement for aggressive degenerative disease in the medial compartment and genu varum. It is not certain whether chondrocalcinosis and medial femoral condyle necrosis are linked aetiologically; however, it would seem that the presence of chondrocalcinosis is an adverse prognostic indicator.

Arthritis in Behcet's syndrome.

The clinical and radiological features of fourteen patients with Behcet's syndrome have been reviewed with particular reference to joint disease. Thirteen patients (93%) suffered recurrent peripheral oligo- or poly-arthritis, this symptom being the presenting complaint in two (14%). There were no radiographic abnormalities in peripheral joints. Ten patients (71%) complained of low back pain and in seven (50%) there was a mild erosive sacro-iliitis. Five patients (36%) had an enthesopathy (calcaneal spurs) one of whom also demonstrated vertebral body squaring. Patients with sacro-iliitis did not possess the HLA B27 antigen. Behcet's syndrome should be entertained in the radiological differentiation of sacro-iliitis with a clinical arthropathy.

Bone scintigraphy and radiography in the early recognition of diabetic osteopathy.

Twenty-seven diabetic patients with clinical evidence of neuropathy were investigated by foot radiography, two-phase bone scintigraphy, biothesiometry and cardiovascular autonomic function testing. Typical signs of diabetic osteopathy on radiography were found in 10 subjects (37%), the degree of radiographic abnormality correlating with the severity of neurological impairment. Furthermore, all diabetics with evidence of severe neuropathy showed some evidence of osteopathy on foot radiographs. In all 10 cases of diabetic osteopathy diagnosed radiographically, abnormalities were shown on scintigraphy. In addition, five other patients showed scintigraphic abnormalities, without corresponding changes on radiography, and in this group the neurological impairment was less severe. Although confirmatory longitudinal studies are necessary, it seems likely that the earliest changes of diabetic neuropathic osteopathy may thus be recognized on bone scintigraphy, at a time when conventional radiographs are normal. This stage of diabetic osteopathy is associated with a lesser degree of neurological impairment.

Tibial stress fracture in pyrophosphate arthropathy.

Five elderly patients with chronic pyrophosphate arthropathy developed stress fractures of the tibia. All patients had deformed, painful knees with the result that their increasing symptoms were not readily attributed to a stress fracture. Such a possibility should be considered in patients with chronic pyrophosphate arthropathy since early recognition makes management of the stress fracture easier.

Arthritis or arteritis.

Diagnosing Polymyalgia Rheumatica (PMR) or Giant Cell Arthritis (GCA) on an established background of arthritis is fraught with difficulties. We describe one such case.

Prostaglandin E1 infusion for small vessel arterial ischaemia.

The effects on severe arterial ischaemia of infusions of Prostaglandin E1 (PGE1) a vasodilator and inhibitor of platelet aggregation, were studied in 49 patients (aged 17-80). Criteria for patient selection included rest pain and/or digital ulceration and gangrene secondary to predominantly small vessel disease. PGE1 was infused at a low (6 ng/kg/min), intermediate (10 ng/kg/min) or high (14 ng/kg/min) dose rate via a central venous cannula on 52 occasions without serious side effects. Doppler studies, pulse volume recordings and infra red radiometry were used to quantify the clinical effects. Improvements in digital perfusion were demonstrated by increased pulse volume amplitude (7.1 +/- 1.1 to 21.6 +/- 2.7 mm mean +/- SEM) which remained significantly raised at 6 weeks (14.2 +/- 2.9 mm; P = less than 0.001 paired t test). Infra red digital temperatures were also significantly raised 6 weeks post infusion (27.2 +/- 0.6 degrees C to 29.5 +/- 0.6 degrees C; P less than 0.001). The majority of patients reported improvement in pain, and two thirds of 12 superficial ulcers healed in 6 weeks. These results show that PGE1, improves digital perfusion for several weeks in patients with severe arterial ischaemia.