Patient-led training on patient safety: a pilot study to test the feasibility and acceptability of an educational intervention.

BACKGROUND: Training in patient safety is an important element of medical education. Most educational interventions on patient safety training adopt a 'health-professional lens' with limited consideration on the impact of safety lapses on the patient and their families and little or no involvement of patients in the design or delivery of the training. AIMS: This paper describes a pilot study to test the feasibility and acceptability of implementing a patient-led educational intervention to facilitate safety training amongst newly qualified doctors. METHOD: Patients and/or carers who had experienced harm during their care shared narratives of their stories with trainees; this was followed by a focused discussion on patient safety issues exploring the causes and consequences of safety incidents and lessons to be learned from these. RESULTS: The intervention, which will be further tested in an NIHR-funded randomised controlled trial (RCT), was successfully implemented into an existing training programme and found acceptance amongst the patients and trainees. CONCLUSION: The pilot study proved to be a useful step in refining the intervention for the RCT including identifying appropriate outcome measures and highlighting organisational issues.

Clinical and radiographic disease course of hand osteoarthritis and determinants of outcome after 6 years.

OBJECTIVE: To investigate the long-term clinical and radiographic disease course of hand osteoarthritis (OA) and determinants of outcome. METHODS: Clinical and radiographic measures were obtained at baseline and after 6 years in 289 patients with hand OA (mean age 59.5 years, 83.0% women). Clinical outcomes were self-reported pain and functional limitations assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). Poor clinical outcome was defined as a follow-up score not fulfilling the Patient Acceptable Symptom State. Radiographic outcome was assessed by osteophytes and joint space narrowing (JSN) on standardised hand radiographs using the Osteoarthritis Research Society International (OARSI) atlas. Radiographic progression was defined as a change in osteophytes or JSN, above the smallest detectable change. Change in outcome measures was calculated and baseline determinants for poor clinical outcome and radiographic progression were assessed using logistic regression analysis. RESULTS: Clinical change showed great variation, with half of the population reporting deterioration. Poor outcome in pain was related to high levels of functional limitations and a high number of painful joints at baseline. Poor outcome on functional limitations was related to high baseline pain levels. Radiographic progression was present in 52.5% of patients and associated with high baseline levels of pain, nodes, osteophytes and the presence of erosive OA and nodal OA. Clinical change and radiographic progression were not related. CONCLUSIONS: This study gives insight in the clinical and radiographic course of hand OA as well as determinants of outcome. These findings enable better patient information on prognosis. The relationship between clinical and radiographic outcome needs further investigation.

Systemic and local factors are involved in the evolution of erosions in hand osteoarthritis.

OBJECTIVE: In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. METHODS: The 6-year evolution in radiographic Verbruggen-Veys anatomical phase was assessed in interphalangeal joints of 236 patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase transitions from non-erosive to erosive phases and from active erosions to remodelling. Clustering of erosive evolution within patients was assessed using the χ² test. Familial aggregation was evaluated in sibling pairs by estimating ORs for siblings and probands sharing erosive evolution. Local baseline determinants and the effect of high sensitivity C reactive protein were assessed using generalised estimating equations. RESULTS: Erosive evolution took place in 181 of 4120 interphalangeal joints at risk (4.4%), corresponding to 60 patients (25.4% of study sample). Erosive evolution was found more often in multiple interphalangeal joints in one patient than would be expected by chance (χ² 373.0, p < 0.001). The adjusted OR (95% CI) for a sibling having erosive evolution if the proband had erosive evolution was 4.7 (1.4 to 15.8). Systemic inflammation was not associated with erosive activity. Independent local determinants were joint space narrowing (OR (95% CI) 8.9 (4.8 to 16.4)) and self-reported pain (OR (95%CI) 2.3 (1.1 to 4.7)). CONCLUSIONS: rosive evolution was clustered within patients and families. Local factors were also involved in the evolution. This increase in insight in the pathogenesis of erosive hand OA will contribute to the development of new treatments.

Accelerated metacarpal bone mineral density loss is associated with radiographic progressive hand osteoarthritis.

OBJECTIVE: To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. METHODS: Using the Kellgren-Lawrence (KL) grading scale and the Osteoarthritis Research Society International Atlas, standardised hand radiographs of 181 patients with primary OA at multiple sites (mean age 60 years, 80% women, mean body mass index 27 kg/m(2)) were assessed for hand OA at baseline (KL ≥ 2 in two or more hand joints) and progressive hand OA over 2 years (≥ 1 point increase in total osteophyte and joint space narrowing score in patients with hand OA at baseline). Changes in BMD were measured over 2 years in metacarpals 2-4 by digital x-ray radiogrammetry. Accelerated BMD loss was defined as loss of >3 mg/cm(2)/year. Logistic regression analyses were performed to assess the associations between BMD loss and progressive hand OA. RESULTS: The baseline prevalence of hand OA was 68% and, after 2 years, 32% of these patients had progressive hand OA. Accelerated BMD loss was present in 79% of the patients with progressive hand OA compared with 60% and 57% of the patients with non-progressive hand OA and no hand OA, respectively. BMD loss was independently associated with progressive hand OA compared with non-progressive hand OA with a RR (95% CI) of 2.1 (1.1 to 4.3). CONCLUSION: Accelerated metacarpal BMD loss is associated with progressive hand OA over a period of 2 years; knowledge of common mechanisms may lead to development of therapeutic interventions for hand OA.

European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis.

OBJECTIVES: To agree terminology and to develop recommendations for the diagnosis of calcium pyrophosphate deposition (CPPD). METHODS: The European League Against Rheumatism (EULAR) CPPD Task Force, comprising 15 experts from 10 countries, agreed the terms and recommendations for diagnosis of CPPD using a Delphi consensus approach. Evidence was systematically reviewed and presented in terms of sensitivity, specificity and positive likelihood ratio (LR) to support diagnosis; ORs were used for association. Strength of recommendation (SOR) was assessed by the EULAR visual analogue scale. RESULTS: It was agreed that 'CPPD' should be the umbrella term that includes acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis (OA) with CPPD and chronic CPP crystal inflammatory arthritis. Chondrocalcinosis (CC) defines cartilage calcification, most commonly due to CPPD and detected by imaging or histological examination. A total of 11 key recommendations were generated on the topics of clinical features, synovial fluid (SF) examination, imaging, comorbidities and risk factors. Definitive diagnosis of CPPD relies on identification of SF CPP crystals. Rapid onset inflammatory symptoms and signs are suggestive but not definitive for acute CPP crystal arthritis. Radiographic CC is not highly sensitive or specific, whereas ultrasonography appears more useful (LR=24.2, 95% CI 3.51 to 168.01) for peripheral joints. Recognised risk factors for CPPD include ageing, OA and metabolic conditions such as primary hyperparathyroidism, haemochromatosis and hypomagnesaemia; familial forms are rare. SORs varied from 53 to 99 (maximum 100). CONCLUSION: New terms for CPPD were agreed and 11 key recommendations for diagnosis of CPPD were developed using research evidence and expert consensus.

Reliability, sensitivity to change and feasibility of three radiographic scoring methods for hand osteoarthritis.

OBJECTIVE: To compare the reliability, sensitivity to change and feasibility of three radiographic scoring methods for hand osteoarthritis (OA). METHODS: Baseline, 2-year and 6-year hand radiographs of 90 patients with hand OA were read in triplicate in chronological order by three readers from different European centres using the OARSI atlas (OARSI), Kellgren--Lawrence grading scale (KL) and Verbruggen--Veys anatomical phase score (VV). Reliability was determined using intraclass correlation coefficients and smallest detectable change (SDC). Sensitivity to change was assessed by the proportion of progression above the SDC. Feasibility was reflected by the mean performance time. RESULTS: Intra- and inter-reader reliability was similar across methods. Inter-reader SDCs (% maximum score) for KL, OARSI and VV were 2.9 (3.2), 4.1 (2.9) and 2.7 (1.8) over 2 years and 3.8 (4.1), 4.6 (3.3) and 4.0 (2.5) over 6 years, respectively. KL detected a slightly higher proportion of progression. There were differences between readers, despite methods to enhance consistency. The mean performance time (SD, minutes) for KL, OARSI and VV was 4.3 (2.5), 9.3 (6.0) and 2.8 (1.5), respectively. CONCLUSION: Methods had comparable reliability and sensitivity to change. Global methods were fastest to perform. For multicentre trials use of a central reading centre and multiple readers may minimise inter-reader variation.

EULAR recommendations for calcium pyrophosphate deposition. Part II: management.

OBJECTIVES: To develop evidence-based recommendations for management of calcium pyrophosphate deposition (CPPD). METHODS: A multidisciplinary guideline development group of 15 experts, representing 10 European countries, generated key propositions for management of CPPD using a Delphi consensus approach. For each recommendation research evidence was searched systematically. Whenever possible, the effect size and number needed to treat for efficacy and RR or OR for side effects were calculated for individual treatment modalities. Strength of recommendation was assessed by the European League Against Rheumatism visual analogue scale. RESULTS: Nine key recommendations were generated, including topics for general management, treatment of acute attacks, prophylaxis against recurrent acute attacks and management of chronic symptoms. It was recommended that optimal treatment requires both non-pharmacological and pharmacological treatments. For acute CPP crystal arthritis, cool packs, temporary rest and joint aspiration combined with steroid injection are often sufficient. For prophylaxis or chronic inflammatory arthritis with CPPD, oral non-steroidal anti-inflammatory drugs with gastroprotective treatment and/or low-dose colchicine 0.5-1.0 mg daily may be used. Other recommendations included parenteral or oral corticosteroid for acute CPP arthritis in those unresponsive or unsuited to other measures, and low-dose corticosteroid, methotrexate or hydroxychloroquine for chronic inflammatory arthritis with CPPD. Asymptomatic CPPD requires no treatment. Strength of recommendations varies from 79% to 95%. CONCLUSION: Nine key recommendations for management of CPP crystal associated arthritis were developed using both research evidence and expert consensus. Strength of recommendations was provided to assist the application of these recommendations.

Clinical burden of erosive hand osteoarthritis and its relationship to nodes.

OBJECTIVE: To describe the clinical burden of erosive osteoarthritis (EOA) of the hand in terms of pain, functioning and health-related quality of life (HRQL) and its relationship to nodal osteoarthritis (OA). METHODS: Patients with EOA (n=42) and non-EOA (n=194) of the hand were compared. Pain was assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Michigan Hand Outcome Questionnaire (MHQ) and pain intensity upon pressure. Functioning was evaluated with AUSCAN, MHQ, grip strength, pinch grip and hand mobility tests. HRQL was measured with the Short Form-36. Patient satisfaction with hand function and aesthetics were also evaluated. The presence of nodal OA as well as its extent (reflected by the number of nodes) was assessed. Mean differences between patient groups were estimated with linear mixed models. To determine whether differences were independent of the nodal character of the disease, adjustments were made for the number of nodes. RESULTS: Patients with EOA experienced more pain, more functional limitation, less satisfaction with hand function and aesthetics and worse hand mobility than patients with non-EOA. HRQL was similar for the two groups. Patients with EOA had more nodes. A higher number of nodes was associated with worse outcome. After correction for the number of nodes, only hand mobility and patient satisfaction remained different between the groups. CONCLUSION: Patients with EOA have a higher clinical burden than those with non-erosive disease. This higher burden is only partly attributed to the erosive disease itself, but mainly to the nodal character of the disease.

EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis.

OBJECTIVE: To develop evidence-based recommendations for the diagnosis of knee osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 12 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched systematically. Whenever possible, the sensitivity, specificity and likelihood ratio were calculated for individual diagnostic indicators and a diagnostic ladder was developed using Bayes' method. Secondary analyses were undertaken to test directly the recommendations using multiple predictive models in two populations from the UK and the Netherlands. Strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Recommendations covered the definition of knee OA and its risk factors, subsets, typical symptoms and signs, the use of imaging and laboratory tests and differential diagnosis. Three symptoms (persistent knee pain, limited morning stiffness and reduced function) and three signs (crepitus, restricted movement and bony enlargement) appeared to be the most useful. Assuming a 12.5% background prevalence of knee OA in adults aged > or =45 years, the estimated probability of having radiographic knee OA increased with increasing number of positive features, to 99% when all six symptoms and signs were present. The performance of the recommendations in the study populations varied according to the definition of knee OA, background risk and number of tests applied. CONCLUSION: 10 key recommendations for diagnosis of knee OA were developed using both research evidence and expert consensus. Although there is no agreed reference standard, thorough clinical assessment alone can provide a confident rule-in diagnosis.

Treatment with TNF-α inhibitor infliximab might reduce hand osteoarthritis in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-α) inhibitor infliximab on secondary OA in IPJs. METHODS: In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. RESULTS: Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. CONCLUSION: Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-α therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-α in treatment of primary hand OA.

Progression of hand osteoarthritis over 2 years: a clinical and radiological follow-up study.

OBJECTIVES: To investigate the course of hand osteoarthritis over 2 years by currently available outcome measures. METHODS: 189 participants of the Genetics, Arthrosis and Progression (GARP) study with hand osteoarthritis were followed for 2 years. Self-reported hand pain and functional limitations were assessed with the Australian/Canadian osteoarthritis hand index (AUSCAN LK 3.0). Pain intensity upon lateral pressure in the interphalangeal and thumb base joints was graded on a four-point scale. Osteophytes (0-3) and joint space narrowing (JSN) (0-3) was scored at baseline and after 2 years in interphalangeal and thumb base joints. Standardised response means (SRM) were calculated. RESULTS: 172 (91%) patients completed the 2-year follow-up (mean age 60.5 years, 78.5% women). Statistically significant increases in self-reported pain and function scores, in pain intensity scores as well as in osteophyte and JSN total scores were seen over 2 years. SRM were 0.25, 0.23, 0.67, 0.34 and 0.35, respectively, for self-reported pain and function scores, pain intensity scores, osteophyte and JSN total scores. Radiological progression was not associated with changes in self-reported pain and function. Women in an early post-menopausal stage were especially at risk of progressing radiologically. CONCLUSIONS: Currently available outcome measures were able to assess progression over the relatively short time period of 2 years. Radiographic outcomes were more responsive than self-reported outcomes. Pain intensity upon lateral pressure seems to be a responsive measure but needs validation.

EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT.

OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

Innate production of tumour necrosis factor alpha and interleukin 10 is associated with radiological progression of knee osteoarthritis.

OBJECTIVES: Inflammation may contribute to progression of knee osteoarthritis (OA). Therefore, we investigated whether innate differences in the inflammatory response regarding cytokine production were associated with radiological progression of knee OA. METHODS: Symptomatic patients with knee OA (n = 89) were included. Standardised posteroanterior knee radiographs were obtained at baseline and after 24 months. Medial and lateral tibiofemoral joint space narrowing (JSN) was graded with the Altman atlas. Radiological progression was defined as an increase of at least one score in JSN total scores. Whole blood samples were stimulated with lipopolysaccharide (LPS) (10 ng/ml). Relative risks (RR) with 95% CIs of OA progression in relation to quartiles of innate ex vivo production of interleukin (IL)1beta, tumour necrosis factor (TNF)alpha, IL1 receptor antagonist (Ra) and IL10 were calculated. RESULTS: Progression of JSN was present in 29 (33.7%) of 86 followed patients after 2 years. Patients in the highest quartile of TNFalpha production had a sixfold increased risk of JSN progression (age, sex and body mass index adjusted RR 6.1, 95% CI 1.4 to 9.8) and patients in the highest quartile of IL10 production had a fourfold increased risk of JSN progression (age, sex and body mass index adjusted RR 4.3, 95% CI 1.7 to 6.2), both in comparison with those patients in the lowest quartile. No significant associations were found between variations in IL1beta and IL1Ra production and JSN progression. CONCLUSION: The innate capacity to produce TNFalpha and IL10 upon LPS stimulation is associated with radiological progression of knee OA, even over a relatively short follow-up period of 2 years.

The development of a preliminary ultrasonographic scoring system for features of hand osteoarthritis.

OBJECTIVES: Painful osteoarthritis (OA) of the hand is common and a validated ultrasound (US) scoring system would be valuable for epidemiological and therapeutic outcome studies. US is increasingly used to assess peripheral joints, though most of the US focus in rheumatic diseases has been on rheumatoid arthritis. We aimed to develop a preliminary US hand OA scoring system, initially focusing on relevant pathological features with potentially high reliability. METHODS: A group of experts in the fields of OA, US and novel tool development agreed on domains and suggested scaling of the items to be used in US hand OA scoring systems. A multi-observer reliability exercise was then performed to evaluate the draft items. RESULTS: Synovitis (grey scale and Power Doppler) and osteophytes (representing activity and damage domains) were included and evaluated as the initial components of the scoring system. All three features were evaluated for their presence/absence and if present were scored using a 1-3 scale. The reliability exercise demonstrated intra-reader kappa values of 0.444-1.0, 0.211-1.0 and 0.087-1.0 for grey scale synovitis, power Doppler and osteophytes respectively. Inter-reader reliability kappa values were 0.398, 0.327 and 0.530 grey-scale synovitis, power Doppler and osteophytes respectively. Without extensive standardisation, both intra- and inter-reader reliability were moderately good. CONCLUSIONS: The draft scoring system demonstrated substantive to almost perfect percentage exact agreement on the presence/absence of the selected OA features and moderate to substantive percentage exact agreement on semi-quantitative grading. This preliminary process provides a good basis from which to further develop an US outcome tool for hand OA that has the potential to be utilised in multicentre clinical trials.

Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES: Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field. REVIEW METHODS: A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms. RESULTS: The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year. CONCLUSIONS: The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.

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.

Paget's disease in an archeological population.

The aim of this investigation was to study the prevalence and distribution of Paget's disease in an archeological population. Paget's disease, first described over 100 years ago, is a well-recognized chronic disorder involving abnormal bone turnover with established radiological features. Prevalence within modern populations varies both within individual countries and between them. Paleopathological examples are uncommon and sporadically reported both from Europe and the Americas and from many periods of history. A large skeletal assemblage (2,770 individuals) from Barton on Humber, UK, provided an opportunity to examine the prevalence of Paget's disease in one area of the northern England over the period 900-1,850 AD. All bones were examined visually for evidence of Paget's disease of the bone (PDB) and all abnormal bones were examined further by plain radiography. Fifteen cases of probable Paget's disease were found. The overall prevalence was 2.1% in those aged >40 years. The prevalence before 1500 AD was 1.7% and post-1500 AD was 3.1%. The distribution of disease mirrored modern disease, with the lumbar spine, pelvis, and proximal femur being the commonest sites. The prevalence of Paget's disease in the United Kingdom over the last 1,000 years has been assessed. Although there is a trend of increasing prevalence, this did not reach statistical significance. This is likely caused by the small sample size, but this is by far the greatest number of cases of PDB described in a single skeletal assemblage to date. The distribution of lesions within the skeleton is unchanged.

The effect of etomidate on adrenocortical function in dogs before and during hemorrhagic shock.

The effects of the hypnotic agent ethyl phenylethyl imidazole carboxylate (etomidate), on corticosteroidogenesis were studied in greyhound dogs during a 2-h period of anesthetic followed by a further 2 h of anesthetic combined with hemorrhage. Three groups of dogs were studied. The first, a control, received thiopentone and pentobartitone for induction and maintenance of anesthesia. A second control group received the chemically unrelated hypnotic preparation, althesin, after induction with thiopentone and pentobarbitone. In the first control group and the althesin-treated control group, changes in plasma ACTH and in plasma renin and angiotensin II concentrations were followed closely by changes in the levels of their respective dependent corticosteroids. A third experimental group received etomidate after induction of anesthesia with thiopentone and pentobarbitone. In these, in contrast, plasma levels of progesterone, 17 alpha-hydroxyprogesterone, corticosterone, cortisol, and aldosterone decreased during the experiment even failing to respond to massive rises in plasma ACTH concentration, renin, and angiotensin II levels after hemorrhage. However, the ability of 11-deoxycortisol and 11-deoxycorticosterone to respond was retained. These results suggest that etomidate inhibits corticosteroidogenesis directly, probably acting at more than one point in the biosynthetic pathway. It is suggested that it inhibits mitochondrial steroid hydroxylation (e.g. side chain cleavage, 11 beta-hydroxylation), but not 21-hydroxylation which occurs outside the mitochondrion.

The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations.

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.

Treatment of rheumatoid arthritis patients with interleukin-1 receptor antagonist: radiologic assessment.

OBJECTIVES: The radiologic findings of a placebo-controlled, dose-ranging, multicenter, multinational trial have been reported previously. Radiographs were evaluated using the Larsen scoring method and Erosion Joint Count. After completion of the study, a subset of the films was read again using a modified Sharp score. This article will focus on the methodologies, scoring indices, and outcomes of the Larsen and Erosion Joint Count evaluations. Modified Sharp scores are presented in a separate article. METHODS: A 6-month, phase II, randomized, double-blind, placebo-controlled trial was conducted involving 472 patients with active rheumatoid arthritis. Patients from 41 centers in 11 countries were randomly selected to receive 30 mg/d, 75 mg/d, or 150 mg/d of recombinant human interleukin-1 receptor antagonist (IL-1ra) subcutaneously daily or placebo. Radiographic criteria were circulated to all centers, and the same 2 radiologists used the Larsen score and the Erosion Joint Count to score what was essentially a homogeneous film collection. At the completion of the study, a subset of radiographs also was read using the Genant-modified Sharp score. Patients in any of the treatment arms had the option of continuing in an extension trial for an additional 6 months, and those in the placebo arm had the option of being randomly placed into one of the treatment arms. RESULTS: The Larsen and Erosion Joint Count data from these patients confirm that at 24 weeks, patients receiving placebo worsened by an average of 6.49 Larsen units, whereas those receiving 30, 75, or 150 mg/d of IL-1ra worsened by 3.53, 4.19, and 3.90 Larsen units, respectively. Overall, patients receiving therapy worsened by an average of 3.86 units, achieving statistical significance versus placebo (P = .034). These data are not significantly different from those of the main trial. Mean values were ANOVA-adjusted for country and treatment-group interactions. Similarly, the Erosion Joint Count in placebo patients worsened by an average of 2.64, whereas those receiving 30, 75, or 150 mg/d of IL-1ra worsened by 1.46, 1.05, and 1.70, respectively. The overall therapy and 75 mg/d arm achieved significance versus placebo (P = .002 and P < or = .001, respectively). Preliminary data from the extension study indicate continuing benefit. CONCLUSIONS: Treatment with IL-1ra reduced the rate of joint deterioration and development of new bone erosions.