Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis.

OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.

Predictors of outcome in patients with oligoarthritis: results of a protocol of intraarticular corticosteroids to all clinically active joints.

OBJECTIVE: To determine the outcome and the factors that predict the persistence of synovitis following intraarticular corticosteroid injections in patients with recent-onset oligoarthritis. METHODS: Fifty-one patients with < or =5 joints with synovitis (disease duration < or =12 months) were treated with intraarticular injections of methylprednisolone into all joints with clinical synovitis. Predictors of outcome were sought, with the primary end point a complete response (no synovitis on clinical examination) at 12 weeks. RESULTS: Patient's and physician's assessments of disease activity, the swollen joint count, and function (by Health Assessment Questionnaire) were all significantly improved at 12 weeks (P < 0.001). Twenty-nine patients (57%) were judged to have had a complete response at 2 weeks. The best predictor of response at 12 and 26 weeks was the presence or absence of synovitis at 2 weeks (P = 0.002 and P = 0.004, respectively). At 52 weeks of followup, nearly 50% of the patients still had evidence of synovitis. CONCLUSION: Intraarticular corticosteroids are an effective treatment for early oligoarthritis, but there is still a high level of long-term morbidity. Failure to respond by 2 weeks indicates a high likelihood of persistent disease, and this is relevant when producing management guidelines and selecting patients for studies focusing on early intervention.

Do social factors affect where patients die: an analysis of 10 years of cancer deaths in England.

BACKGROUND: This study investigated whether indices of social deprivation were related to the proportion of cancer patients who died at home. METHODS: Data were derived from death registrations for all cancer deaths 1985-1994 in England. Two indices of deprivation (Underprivileged Area Score (UPA), or Jarman, and Townsend scores) were calculated for each electoral ward; 1991 Census data were used. The scores use combinations of variables, including the percentage in overcrowded homes, the percentage of elderly people living alone, the percentage of one-parent families, etc. A high score indicates more deprivation. The main outcome measures were the proportion (in five and ten year averages) of cancer deaths which occurred at home, calculated for every electoral ward (with populations usually ranging from 5000 to 11,000). Spearman rho was used to test for correlations between the proportion of cancer deaths at home and deprivation score. Electoral wards were categorized by deprivation score into three groups of equal size and analysed over 10 years. Multivariate analysis was used to determine the relative association of different patient based and electoral ward variables with cancer death at home. p < 0.05 (two-tailed) was taken as significant. RESULTS: There were over 1.3 million death registrations from cancer in the 10 years. The proportion who died at home was 0.27, in hospital 0.47, and other setting 0.26. There were wide variations (0.05-0.75) in the proportion of people who died at home in different electoral wards. Small inverse correlations were found between the percentage who died at home and the UPA (-0.35; p < 0.001) and Townsend (-0.26; p < 0.001) scores. The correlations were greatest in North Thames (-0.63, UPA) and smallest in West Midlands (-0.20, UPA). The proportion of home deaths for the different bands of deprivation were: 0.30 (low deprivation), 0.27 (middle deprivation) and 0.24 (high deprivation). Plotting the trends over 10 years suggests no change in this relationship. Multiple regression analysis predicted several ward and patient characteristics and accounted for 30 per cent of the variation. Increased age (patient variable), Jarman score and ethnic minorities (both ward variables) were associated with fewer patients dying at home. Being male and having cancer of the digestive organs were associated with home death. CONCLUSION: There are wide variations in the percentage of cancer deaths at home in different electoral wards. Social factors are inversely correlated with home cancer death, and may explain part of this variation. Home care in deprived areas may be especially difficult to achieve.

Where do cancer patients die? Ten-year trends in the place of death of cancer patients in England.

Although studies have found that 50-70% of cancer patients would prefer to die at home, there has been a trend towards the hospitalization of the dying in many countries. No study has attempted to analyse the changes in place of death in detail. The aim was to analyse the 10-year trends in place of death of cancer patients, by region and by diagnosis, within England. To do this, data on the place of death and patients' characteristics were derived from death registrations for all cancer deaths between the years 1985-94. We examined trends in the place of death for the whole of England, for each region separately and for the main cancer diagnoses. The results show that there were over 1.3 million death registrations from cancer during the 10 years. The mean age increased over the period from 69.9 years in 1985, to 71.3 years in 1994. The percentage who died in a UK National Health Service (NHS) hospital or nursing home fell gradually from 58% (1985) to 47.3% (1994), while the percentage who died in non-NHS hospitals, nursing homes, hospices and communal establishments increased. The percentage who died at home fell slightly but steadily between 1985 and 1992 from 27% to 25.5% and since then increased slightly to 26.5% in 1994. The percentage of home deaths was lowest in the two Thames regions (less than 25%) and highest in the West Midlands, Anglia and Oxford (over 29%). These differentials were maintained across age groups and diagnoses. Older people and women were less likely to die at home than younger people and men. Significant trends showing an increase in home deaths were found in two regions: North Thames and South Thames. Patients with cancers of the lung, colorectum, respiratory organs, bone or connective tissue and lip, oral cavity and pharynx were more likely to die at home (over 29% in 1994) than patients with cancers of the (breast (women, 25% in 1994) or the lymphatic or haematological system 16% in 1994). It can be concluded that the trend towards a reducing home death rate from cancer in England appears to have halted, although this varies between regions. This has implications for primary care services. Although hospital is still the most common place of death from cancer, the percentage of cancer patients who die in hospital is reducing. The largest rise is in the increasing use of hospices and communal establishments, including residential and nursing homes. Given the ageing population, this trend is likely to continue.