Comparison of low-dose rofecoxib versus 1000 mg naproxen in patients with osteoarthritis. Results of two randomized treatment trials of six weeks duration.

OBJECTIVE: To compare the efficacy and safety of rofecoxib 12.5 mg once daily to naproxen 500 mg twice daily in patients > or = 40 years of age with knee or hip osteoarthritis (OA). METHOD: Two identical 6-week, randomized, double-blind studies were conducted (1 in Africa, Australia, Europe, Canada, Mexico, & South America; 1 in Asia). Primary endpoints were pain walking on a flat surface, patient global assessment of response to therapy, and investigator global assessment of disease status. RESULTS: Overall, 944 patients participated. For all efficacy endpoints, treatment effects for rofecoxib and naproxen were comparable and seen at the first measures of efficacy. Both compounds were generally well-tolerated, with an improved gastrointestinal safety profile for rofecoxib versus naproxen. CONCLUSIONS In these studies, rofecoxib 12.5 mg once daily (the lowest indicated dose) and naproxen 500 mg twice daily showed similar treatment effects in OA patients. Rofecoxib and naproxen were generally well tolerated.

Current features of peptic ulcer disease in Finland: incidence of surgery, hospital admissions and mortality for the disease during the past twenty-five years.

BACKGROUND: Medical therapy of peptic ulcer disease (PUD) has improved dramatically during the past 20 years with the introduction of modern antisecretory drugs as well as eradication therapy of Helicobacter pylori. During the 1990s, there has been a 3-fold increase in the consumption of histamine-2-receptor antagonists and proton-pump inhibitors, but also an 8-fold increase in the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) in Finland. METHODS: The incidence of surgery, hospital admissions and mortality for PUD was analysed between 1972 and 1999; the data were collected from the National Research and Development Centre for Welfare and Health and from the National Centre for Statistics. In the analysis, the codes of the Intemational Statistical Classification of Diseases 8-10 were used. RESULTS: In 1987, 11.9 elective operations (per 10(5) inhabitants) were performed (mean of 2 consecutive years), but only 1.3 in 1997, a reduction of 89%. In 1987, 5.2 emergency operations for ulcer perforation or bleeding were performed, whereas there were 7.5 in 1997, an increase of 44%. The annual hospital admission rate increased from 38.3 admissions (per 10(5) inhabitants) in 1972 (mean +/- s (standard deviation) of 5 consecutive years) to 68.7 in 1992. This 79% increase was mainly due to bleeding from gastric ulcer in elderly women. The overall annual mortality rate increased between 1972 and 1992 from 6.4 to 8.4 deaths (per 10(5) inhabitants), i.e. by 31%. The mortality rate from ulcer perforation and haemorrhage increased from 4.2 deaths in 1972 to 7.3 deaths in 1992, i.e. by 74%. CONCLUSIONS: The increasing incidence rates of emergency surgery, hospital admissions and mortality for PUD in the 1980s and 1990s have started to decrease in the most recent years in Finland. This epidemiologic change probably reflects both the demographic change and an increased consumption of NSAIDs, among the elderly people, in particular. The most recent epidemiologic change may reflect an increased consciousness about the harmful effects of conventional NSAIDs. Regardless of the constantly occurring emergency surgery, elective surgery for PUD is hardly ever required today.

A cluster of inflammatory rheumatic diseases in a moisture-damaged office.

OBJECTIVE: To describe a cluster of inflammatory rheumatic diseases in an office workplace that suggests the presence of an environmental trigger. METHODS: There had been an indoor air problem in the workplace since the early 1990s. Large areas of the outer walls of the building were found to be moisture-damaged and contaminated by microbial growth. Case histories of the personnel were studied, and their working areas were related to the areas with highest microbial contamination. The incidence of inflammatory rheumatic diseases was compared with the statistics of the same geographic area. RESULTS: Ten patients with inflammatory rheumatic diseases (3 rheumatoid arthritis, 4 ankylosing spondylitis, 2 Sjögren's syndrome, and one of psoriatic arthritis) entitled to specially reimbursed medication were diagnosed in 1987-2000 (seven cases in 1995-1998). The incidence density ratio computed for the period 1987-2000 was 6.8 (95% confidence interval 3.6-13.0) for all office personnel and 13.2 (6.0-29.0) for those working close to the wall sustaining the worst damage. CONCLUSION: The accumulation of chronic inflammatory rheumatic diseases in a single workplace suggests that some environmental exposure in this damp office had triggered the diseases.

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders.

Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building. Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-alpha in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure. The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 microg x mL(-1), range 0-206.5 microg x mL(-1)), as compared to that during vacation (0.4 microng x mL(-1) range 0-3.7 pg x mL(-1)) (p = 0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p = 0.028). In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

Mortality associated with cervical spine disorders: a population-based study of 1666 patients with rheumatoid arthritis who died in Finland in 1989.

OBJECTIVE: To evaluate the mortality associated with cervical spine deformities in rheumatoid arthritis (RA) based on national data. METHODS: The role of rheumatoid disorders of the cervical spine as a cause of death was studied in 1666 subjects who died in Finland in 1989 and had been entitled under the national sickness insurance scheme to receive reimbursed medication for RA. Death certificates and certificates for drug reimbursement of these 1666 patients and the clinical files of 853 patients were examined for the mention of cervical spine disorders. Thereafter, the cervical spine radiographs and detailed clinical histories of patients with diagnosed cervical spine disorder were evaluated separately. RESULTS: According to the official death certificates, cervical spine disorder was not an underlying, contributory or immediate cause of death in any of these patients. Cervical spine abnormalities had been diagnosed only in 38/853 (4.5%) patients. Cervical spine radiographs from 33 patients were available for examination, and in 17 patients cervical spine deformities were found to be severe enough to be a potential cause of fatal complications. Among these 17 cases, four sudden and four postoperative deaths were recorded (one after cervical spine operation) and three patients were suffering from quadriparesis or paraparesis at the time of death. Among the other 16 patients with cervical spine radiographs, the cervical deformities were less severe and their death histories differed from those of the group with more severe deformities. CONCLUSIONS: Cervical spine disorders in RA should be diagnosed early and treated actively to prevent severe and potentially fatal complications. Deaths caused by these disorders are rare, but they should be remembered when the death certificates are written.

Autologous peripheral blood stem cell transplantation in a patient with severe mixed connective tissue disease.

A 65-year old man with mixed connective tissue disease (MCTD) and severe therapy resistant polymyositis was considered for high-dose cyclophosphamide (200 mg/kg) supported by autologous stem cell transplantation (ASCT). During a 21 months follow-up there has been a significant subjective, but objectively only a slight improvement in muscle strength. Initially the levels of serum creatine kinase and serum aldolase normalised, but are at 21 months at about the same level as before ASCT. Based on histopathological examination there is still active myositis. Our case would suggests that this treatment may have some efficacy in MCTD with severe polymyositis although longer follow-up is needed.

Intensive treatment of rheumatoid arthritis reduces need for dialysis due to secondary amyloidosis.

We have analysed changes in the intensity of treatment of patients with rheumatoid arthritis (RA) and its influence on the number of patients with RA and secondary amyloidosis (SA) admitted to dialysis due to end-stage renal disease. The number of visits and patients at the rheumatological outpatient clinic because of RA, the type of medication used in 1988-1997, and the number of patients with RA and SA on dialysis from 1989 to 1999 were extracted from the data set of Kuopio University Hospital. The intensity of treatment could be evaluated as the treated number of patients with RA and the number of visits at the outpatient clinic. Both the numbers increased from 1988 to 1996, patients under treatment from 201 to 550 and visits from 1091 to 2198, respectively. In 1997, the number of patients still increased (n=637), although the number of visits started to decline (n=2054), partly due to better collaboration of health centres. A marked shift from use of only symptomatic treatment or one disease-modifying antirheumatic drug (DMARD) to more common use of immunosuppressants and/or combinations of at least two DMARDs occurred in the five years from 1992 to 1997. In 1988, the figures for only nonsteroidal anti-inflammatory drugs or only glucocorticoids or one immunosuppressive drug were 24%, 8%, and 9%, and in 1997, 4%, 3%, and 22%, respectively. In 1997, 43% of the patients were treated with combinations of two or more DMARDs. The number of patients with RA on dialysis treatment and the number of new admissions each year due to SA decreased from 11 to 2 and from 5 to none, respectively. At the beginning of year 2000 there was only one patient with RA and SA on dialysis.

Stem cell transplantation for treatment of severe autoimmune diseases: current status and future perspectives.

Autoimmune diseases include a heterogeneous group of disorders with variable presentation and severity. Immunosuppressive and immunomodulatory therapies are often used for treatment with considerable success in some cases. These diseases may also be severe and refractory to conventional treatment. Thus more aggressive intervention might be indicated in a subset of patients. Animal studies suggest that high-dose therapy supported by stem cell transplantation may lead to remissions in experimental autoimmune disease models. Anecdotal case reports suggest that the same may be the case in some human autoimmune diseases as well. This review attempts to summarise some current concepts and future perspectives on stem cell transplantation in the treatment of severe autoimmune diseases.

Reduced incidence of alcohol related deaths in subjects with rheumatoid arthritis.

OBJECTIVES: It has previously been shown that people with ankylosing spondylitis have an increased incidence of alcohol related deaths from accidents and violence. This study investigated alcohol related deaths in subjects with rheumatoid arthritis (RA). METHODS: The study covered the subjects, 1666 in number, who had died in 1989 and had been entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for RA. RESULTS: There were eight alcohol related deaths among the 480 men and three deaths among the 1186 women with RA. The standardised mortality ratios and their 95% confidence intervals (CI) were 0.40 (95% CI 0.20, 0.80) and 0.40 (95% CI 0.13, 1.26), respectively. CONCLUSION: Alcohol either protects from RA or, subjects with RA curtail their drinking after the manifestation of RA.

Hypersensitivity to gold in gold sodium thiomalate-induced dermatosis.

Gold compounds are widely used in the treatment of rheumatoid arthritis. Mucocutaneous side-effects leading to the discontinuation of medication are common with these drugs. We investigated whether allergic mechanisms are involved in dermatosis induced by gold sodium thiomalate (GSTM). Thirteen gold dermatosis patients, 15 arthritis patients without any side-effects from GSTM and 11 healthy controls participated in the study. Venous blood lymphocytes from these subjects were cultured with GSTM and gold sodium thiosulphate (GSTS) in the lymphocyte proliferation test (LPT). In some cases, interferon-gamma-producing cells were enumerated in vitro (T-cell ELISpot). The subjects were also patch-tested with GSTM and GSTS. The LPT to either GSTM, GSTS or both was positive in 12 of 13 patients with gold dermatosis. In the arthritis patient group without side-effects from gold, the LPT gave two false-positive results and in the healthy control group the LPT was falsely positive with one subject. T-cell ELISpot was positive in four of six gold dermatosis patients and negative in the arthritis and healthy control groups. Only one patient who also developed contact dermatitis from gold jewellery was positive to gold in the patch test. These results indicate that gold dermatosis is mediated, at least in part, by allergic mechanisms and that the LPT is of value in the diagnosis of gold dermatosis.

Amyloidosis in a nationwide series of 1666 subjects with rheumatoid arthritis who died during 1989 in Finland.

OBJECTIVES: Virtually all studies dealing with the occurrence of amyloidosis in subjects with rheumatoid arthritis (RA) have been based on selected series collected from university clinics. The purpose of the study was to obtain information on the true prevalence of amyloidosis and the role of amyloidosis as a cause of death. METHODS: The study included all 1666 subjects (480 men and 1186 women) who had died in 1989 and had been entitled under the national sickness insurance scheme to receive specially reimbursed medication for RA. RESULTS: Amyloidosis was regarded as an immediate cause or an intervening antecedent cause of death in 64 cases (3.8%) and as a contributory cause of death in 33 cases (2%), corresponding to a prevalence of 5.8%. Amyloidosis had been diagnosed during life in 89 instances and was detected at autopsy in eight instances. Twenty-three (4.8%) of the subjects were men and 74 (6.2%) were women (P = 0.25). Compared with the remaining subjects in the study series, the lifespan of the subjects with amyloidosis was shortened by 7.7 yr. CONCLUSIONS: The prevalence of amyloidosis was lower than apparent from most earlier studies. Monitoring information derived from the Finnish sickness insurance system is a useful way of following trends in the occurrence of amyloidosis complicating RA.

Stem cell transplantation--a treatment for severe rheumatic diseases?--A review.

Rheumatic diseases can be severe and unresponsive to standard therapeutic approaches. Preclinical studies and anecdotal case reports suggest that high-dose immunosuppressive therapy supported by stem cell transplantation may lead to remissions or even cure in various experimental disease models of autoimmunity as well as in some human rheumatic diseases. This review attempts to summarize some preclinical and clinical data on stem cell transplantation in the treatment of severe rheumatic diseases. In addition to practical aspects, some future perspectives are also discussed.

Increased incidence of alcohol-related deaths from accidents and violence in subjects with ankylosing spondylitis.

Subjects with ankylosing spondylitis (AS) have an increased incidence of deaths from accidents and violence, which is due in part, but perhaps not entirely, to the vulnerability of the affected spine to fractures. The present study covered all the 71 subjects (58 men and 13 women) who had died in Finland in 1989 and who were entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for AS. The death certificates of an earlier cohort study dealing with mortality in AS were also re-examined. Sixteen subjects (14 men and two women) in the 1989 mortality series had died of accidents and violence. Nine of the deaths (three accidents, two suicides and four alcohol poisonings) were alcohol related. The relative risk of such deaths in subjects with AS compared to the Finnish population as a whole was 2.64 (95% confidence interval 1.44-4.84). In the cohort study, 16 deaths had been due to accidents and violence, the expected number being 11.4. Eight of the 16 deaths had been alcohol related. Uncontrolled use of alcohol is an important determinant in the surplus of deaths from accidents and violence in Finnish patients with AS.