Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. METHODS: The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. RESULTS: Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. CONCLUSION: Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity.

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. RESULTS: Mean age (years) ±â€¯S.D. at diagnosis was 14.2 ±â€¯2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ±â€¯S.D. was 1.27 ±â€¯1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). CONCLUSIONS: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

[Effectiveness and safety of adalimumab and etanercept for rheumatoid arthritis in a third-level hospital]. / Efectividad y seguridad de adalimumab y etanercept en artritis reumatoide en un hospital de tercer nivel.

OBJECTIVE: To assess the effectiveness of adalimumab and etanercept at 6 and 12 months after therapy onset using DAS28, EULAR (European League Against Rheumatism), and ACR (American College of Rheumatology) criteria, and to analyze safety. METHOD: A prospective, 12-month, observational study of a patient cohort diagnosed with rheumatoid arthritis who were started on adalimumab or etanercept at the Rheumatology Department between January 2003 and December 2004. DAS28, EULAR, and ACR criteria were examined at 6 and 12 months. An intention-to-treat analysis was performed, and adverse reactions were quantitized. RESULTS: Ninety-nine patients were included - 50 on adalimumab and 49 on etanercept. Of these, 30 and 20%, respectively, received monotherapy. No differences in effectiveness were seen between both drugs during the studied periods of time according to DAS28. EULAR response to adalimumab at 6 and 12 months was: good 28 and 38%; moderate 40 and 36%; nil 10 and 4%; regarding etanercept at 6 and 12 months: good 29 and 43%; moderate 31 and 24%; nil 18 and 10%. As regards adalimumab at 6 and 12 months: ACR20: 64 and 62%; ACR50: 44 and 46%; ACR70: 22 and 26%; as regards etanercept at 6 and 12 months: ACR20: 61 and 65%; ACR50: 41 and 45%; ACR70: 16 and 24%. Eleven patients discontinued therapy in each group. CONCLUSIONS: Adalimumab and etanercept had a similar effectiveness in our population. Criteria of use may condition results, and thus awareness of other hospitals experience is encouraged.

Adalimumab for treating rheumatoid arthritis.

BACKGROUND: Adalimumab is a fully human anti-TNFalpha monoclonal antibody. Published studies indicate that its use in patients with RA can be effective and safe. OBJECTIVES: The aim of this review was to assess the efficacy and safety of adalimumab in the treatment of RA. SEARCH STRATEGY: Electronic databases were searched up to August, 2004: MEDLINE, CINAHL, EBM Reviews (CDSR, ACP Journal Club, DARE and CENTRAL) and Health STAR. Conference proceedings were hand searched and pharmaceutical companies were contacted to obtain additional unpublished data from published trials. Adalimumab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. SELECTION CRITERIA: All randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing adalimumab alone or in combination with DMARDs to placebo or other DMARDs. DATA COLLECTION AND ANALYSIS: Two reviewers independently collected the data in a standardized form and assessed the methodological quality of the trial using validated criteria. Outcome measures included ACR and EULAR responses, DAS 28 and components of ACR response and radiographic data. Safety data were also included. Continuous data were reported as weighted mean difference (WMD) with 95% confidence interval (95%CI), absolute benefit (AB) and relative difference (RD). Dichotomous outcomes were reported as relative risk (RR) with 95% CI, absolute risk difference (ARD) or risk difference (RDiff) with 95%CI and number needed to treat (NNT) or to harm (NNH). When significant heterogeneity was not found, data were pooled. MAIN RESULTS: Six studies with 2381 patients were included in this review. Two comparisons were done: A. adalimumab subcutaneously (sc) + methotrexate (or DMARDs) versus placebo sc + methotrexate (or DMARDs). B. adalimumab sc in monotherapy versus placebo sc. In the comparison A, with adalimumab 40 mg every other week (e.o.w.), the RR to achieve an ACR 20 response at 24 weeks ranged in the included studies from 1.52 to 4.63, and the NNT ranged from 1.9 to 5.4. The RR (95%CI) to achieve an ACR 50 response was 4.63 (3.04-7.05), and the NNT was 3.0 (95%CI 2.0-6.0). The RR (95%CI) to achieve an ACR 70 response was 5.14 (3.14-8.41) and the number needed to treat was 7.0 (95%CI 5.0-13.0). At 52 weeks, the RRs (95%CI) to achieve an ACR 20, 50, and 70 response were 2.46 (1.87-3.22), 4.37 (2.77-6.91), and 5.15 (2.60-10.22), with NNTs of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg e.o.w. and 20 mg every week (e.w.) significantly slowed the radiological progression including Sharp modified index, erosion score, and joint space score (only with 40 mg e.o.w.). In the comparison B, with adalimumab 40 mg e.o w. , the RRs to achieve an ACR 20, 50, and 70 response at 24/26 weeks were 1.91 (1.17-3.10), 2.84 (1.58-5.12), and 7.33 (2.25-33.90) with NNTs of 5.0 (95%CI 3.0-9.0), 7.0 (4.0-20.0), and 9.0 (3.0-38.0), respectively. In most of the analysed studies and comparisons, there were not significant differences in safety outcomes between adalimumab and control groups. The development of positive antinuclear antibodies was significantly more frequent in adalimumab patients than in placebo patients. Serious infections were significantly more frequent in adalimumab patients in only one study (Keystone 2004) with a RR (95%CI) of 7.64(1.02-57.18) and a NNH of 30.2. AUTHORS' CONCLUSIONS: On the basis of the studies reviewed here, adalimumab in combination with methotrexate is efficacious and safe in the treatment of the rheumatoid arthritis. Adalimumab 40 mg sc e.o.w. and 20 mg e.w. slows the radiographic progression at 52 weeks. Adalimumab in combination with DMARDs other than methotrexate is also efficacious and safe, even though data from one only study are available and the number of patients in each group is low. Adalimumab in monotherapy is efficacious and safe in the treatment of the rheumatoid arthritis but the effect size is lower than with combined therapy.

Intra-observer reliability of commonly used outcome measures in rheumatoid arthritis.

OBJECTIVE: To determine the reliability of some commonly used outcome measures in patients with rheumatoid arthritis. METHODS: We studied 22 consecutive patients with rheumatoid arthritis enrolled in a clinical trial in a tertiary care center. The study design consisted of a test-retest, in which the same rheumatologist evaluated all of the patients twice, with an interval between evaluations of 90 to 120 minutes. Statistical analysis of the data consisted of calculation of the weighted Kappa (kw) and the intraclass correlation coefficient (ICC). RESULTS: For the Ritchie articular index, kappa w = 0.83, ICC = 0.49, p < 0.0001; tender joint count, kappa w = 0.82, ICC = 0.49, p < 0.0001; physician's global assessment, kappa w = 0.79, ICC = 0.48, p < 0.0001; disease activity score, kappa w = 0.79, ICC = 0.49, p < 0.0001; utilities, kappa w = 0.71, ICC = 0.48, p < 0.0001; swollen joint count, kappa w = 0.7, ICC = 0.47, p < 0.0001; patient's global assessment, kappa w = 0.58, ICC = 0.44, p < 0.0001; pain kappa w = 0.45, ICC = 0.41, p < 0.0001. CONCLUSIONS: The reliability of most of the outcome measures was good. It was higher for those measurements evaluated by a rheumatologist and for the composite indexes. Those requiring patient participation need to be improved.

Risk factors associated with mortality in systemic lupus erythematosus. A case-control study in a tertiary care center in Mexico City.

OBJECTIVE: To identify the mortality risk factors in a group of Mexican patients with SLE. METHODS: A case-control autopsy study in a tertiary care center in Mexico, City. Patients with SLE who died during 1958 to 1994 with an autopsy study were selected as cases, and alive patients matched by age (+/- 3 years), decade of SLE onset, and disease duration (+/- 5 years) were defined as controls. Clinical charts were reviewed looking at clinical variables. SLE disease activity was evaluated with the MexSledai index, and SLE disease severity with the Severity Index. Variables were classified as present at any moment during the follow-up and 3 months before death in cases or cut-off date in controls. STATISTICAL ANALYSIS: matched univariate and multivariate analysis by multiple logistic regression were performed, and the results were presented as odds ratio and 95% confidence intervals (OR, 95%CI). RESULTS: 76 matched pairs of patients were studied. Age, gender, and years offormal education were similar in the cases and controls. Variables associated with mortality three months before death were: lung involvement OR= 15.6, 95%CI (4.8-50.3), p<0.001; severe thrombocytopenia 9.6 (2.9-31.7), p<0.001; heart involvement 5.8 (2.6-13.0), p<0.001; and the severity index (cases 8.8 mu, 2.4 sigma vs controls 3.5, 2.0, respectively) 2.2 (1.5-3.4), p<0.001. Variables associated with mortality detected at any moment before death were kidney involvement 2.16 (1.09-4.29), p<0.02; the steroid therapeutic index 2.3 (1.2-4.5), p<0.001; number of previous admissions 2.4 (1.4-4.3), p<0.001; the MEX-SLEDAI index (cases 21.6 mu 6.3 sigma vs controls 12.6, 5.8), 1.2 (1.1-1.3), p<0.001; and the number of severe infections 14.4 (4.4-46.2), p<0.001. Protective variables were skin involvement 0.1 (0.3-0.6), p<0.001; daily dose of chloroquine (cases 3.9 mu, 24.1 sigma vs controls 39.4, 60.0 mg), p <0.0001 and the time from thefirst SLE symptom to the patient's demise or the cut-off date 0.7(0.6-0.9), p<0.001. Multiple logistic regression showed that the model which best explained mortality consisted of a severity index 2.6 (1.7-3.8), p<0.001; heart disease 6.5 (1.5-28.2), p=0.01, and steroid therapeutic index 3.3 (1.6-6.6), p=0.001. CONCLUSIONS: An active SLE with multi-organic involvement, steroids and infections were associated with mortality in Mexican patients with lupus attended in a tertiary care center A protective effect of cutaneous disease and chloroquine use was observed.

Mycobacterium tuberculosis infection in patients with systemic rheumatic diseases. A case-series.

OBJECTIVE: To describe the clinical characteristics of patients with systemic rheumatic diseases and tuberculosis. A retrospective case series from 1987 to 1994, drawn from a tertiary-care hospital in Mexico City, was studied. RESULTS: Thirty patients were included (20 women, 10 men), with mean age of 39.8 years (range 14-66), and a mean duration of the systemic rheumatic disease of 44 months (1-372). The rheumatic diseases included systemic lupus erythematosus (SLE) (n = 13), rheumatoid arthritis (7), polymyositis or dermatomyositis (5), and other diseases (5). During the six months previous to the diagnosis of tuberculosis, 22 patients had received corticosteroids, and 13 others immunosuppressants. Mycobacterium tuberculosis was isolated from 18 patients. Pulmonary tuberculosis was found in 10 patients, and extrapulmonary tuberculosis in 20, seven of these with miliary disease. SLE was seen in 6 of the patients with miliary tuberculosis. The clinical manifestations were: fever (67%), weight loss (67%), diaphoresis (60%), cough and sputum (53%), lymph node enlargement (43%), and dyspnea (33%). Sixteen patients had an abnormal chest film. Of 18 patients tested by PPD RT-2, 8 had an induration > 10 mm. Patients were initially treated with 3 or 4 anti-tuberculosis drugs for 15 days to 6 months, followed by 6 to 10 months of isoniazid plus rifampicin. Three relapsed, and 2 died of respiratory failure. CONCLUSIONS: This case series showed a particular pattern of tuberculosis in patients with systemic rheumatic diseases.

Tuberculosis prophylaxis in patients with steroid treatment and systemic rheumatic diseases. A case-control study.

OBJECTIVE: The aim of this study was to assess the impact of isoniazid prophylaxis in patients with systemic rheumatic diseases who attended a teaching hospital in Mexico City between 1987 and 1992. METHODS: In this case-control study, patients with systemic rheumatic diseases and tuberculosis (cases) were compared with patients with systemic rheumatic diseases without tuberculosis (controls). The groups were matched by year of hospital admission and rheumatic disease. Clinical charts were reviewed for: 1) isoniazid prophylaxis, defined as the administration of isoniazid 300 mg/day for 6 or more months in patients with exposure to steroids (prophylaxis with isoniazid was defined as complete, incomplete or any prophylaxis); 2) exposure to steroids: defined as the administration of prednisone > 15 mg/day (or its equivalent of another steroid) for 3 or more months before tuberculosis or recruitment into the study; 3) exposure to immunosuppressants, defined as the administration of any dose of azathioprine, methotrexate, cyclophosphamide, and/or 6-mercaptopurine, before tuberculosis in the cases or recruitment date in the controls; 4) reactivity to PPD; and 5) other relevant variables. RESULTS: Twenty cases and 66 controls were studied. A 70% decrease in the risk of developing tuberculosis was found among patients who received any prophylaxis with isoniazid as compared to controls: OR 0.31, 95% CI 0.09-0.98, p = 0.03. A 97% decrease was seen in those patients who received complete prophylaxis: OR 0.034, 95% CI 0.0001-0.216, p < 0.0001. The protective effect of complete prophylaxis persisted even after controlling for other potential confounders, such as age, gender, rheumatic disease, duration of rheumatic symptoms, and exposure to steroids and/or immunosuppressants. CONCLUSION: The results of this study suggest that in countries with a high prevalence of tuberculosis the use of isoniazid (300 mg/day for 6 months) in rheumatic patients with exposure to prednisone (> 15 mg/day for three or more months) may be useful to prevent tuberculosis, independently of the results of the PPD reactivity test. However, a controlled clinical trial will be required to confirm these results.

[Non rheumatic pulmonary hemorrhage: case series description]. / Hemorragia pulmonar de causa no reumática: descripción de una serie de casos.

INTRODUCTION: Pulmonary hemorrhage (PH) is characterized by diffuse hemorrhage from the pulmonary microvasculature. Its main features are dyspnea, hemoptysis, diffuse bilateral alveolar infiltrate and sudden fall in hemoglobin. Because the conditioning causes can be both: rheumatic and non-rheumatic, early recognition of the precipitating causes aids in orienting specific therapy. OBJECTIVE: To identify the clinical and paraclinical features of non-rheumatic PH and determine the associated mortality. METHODS: The charts of all patients diagnosed with HP in this institution between 1987 and 1997 were reviewed. OPERATIVE DESCRIPTIONS (DEFINITION): HP was confirmed by bronchoscopy, pulmonary biopsy, necropsy or at least three of the following criteria: a.--Sudden dyspnea, b.--Hemoptysis, c.--Hb decrease of 1 g/dL or more, d.--Recent alveolar infiltrate in the chest X-ray. STATISTICAL ANALYSIS: Descriptive statistics. RESULTS: Nine cases of non rheumatic PH were identified. Median age of patients was 34 years. Six cases corresponded to men, chemotherapy was associated in three patients. The duration from diagnosis of the underlying disease to HP was one to 73 months. All the patients presented dyspnea, crepitant ates tachycardia, decrease in Hb (median 2 g/dL), hypoxemia a mean of 53.4 mmHg. A diffuse interstitial pattern was evident in X rays of six cases; bronchoscopy was performed in three. Seven patients died, six because of massive pulmonary hemorrhage as the direct cause of death and one because of ARDS. CONCLUSIONS: PH occurs in hematological diseases accompanied by severe thrombocytopenia and progressive pulmonary infections. Because its associated with high mortality, early detection and treatment are of utmost importance.

Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid arthritis. A systematic review.

OBJECTIVE: To estimate the proportion of rheumatoid arthritis (RA) patients on anti-tumour necrosis factor (anti-TNF) who require dose escalation. METHODS: Systematic review of the scientific literature. Infliximab, etanercept and adalimumab studies in RA were considered. Primary outcome was the proportion of patients requiring dose escalation. American College Rheumatology (ACR) and Disease activity score (DAS) responses post-escalation were assessed when available. RESULTS: From 1801 references, 16 studies with 8510 patients were included. Of all the infliximab patients, 53.7% underwent dose escalation. Fourty-four per cent of the infliximab patients experienced dose increase and 8.3%, frequency increase. The ACR20 response to dose escalation ranged from 27 to 36% and DAS28 improved from 5.2 to 4.5 in one study and from 4.1 to 3.7 in another. Of the etanercept patients, 17.5% experienced a dose increase but changes on the mean dose were not statistically significant. CONCLUSIONS: Dose escalation is common in patients treated with infliximab, and less frequent with etanercept. In a proportion of patients, the dose escalation seems effective. The design and evidence level of the available studies limit the strength of the conclusions.

[Cross-cultural adaptation and validation of a Spanish version of a specific instrument to measure health-related quality of life in patients with ankylosing spondylitis]. / Adaptación transcultural y validación de una versión en español de un instrumento específico para medir calidad de vida relacionada con la salud en pacientes con espondilitis anquilosante: el ASQoL.

OBJECTIVE: To make a cross-cultural adaptation and validation of a version in Spanish of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) for assessing the health-related quality of life (HRQL) of patients with Ankylosing Spondylitis (AS). PATIENTS AND METHODS: A cross-sectional study with test-retest. AS patients (modified New York criteria) were included. Cross-cultural adaptation was done. Construct validity was assessed comparing the ASQoL scores with the SF-36 and EuroQol scores and diseaserelated variables. Internal consistency and reliability (test-retest) were assessed. Feasibility was assessed by the time spent to complete the questionnaire and the number of items without answer. Spearman correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis test were used in the statistical analysis. Cronbach́alpha coefficient and statistic kappa were used for assessing internal consistency and reliability. RESULTS: Fifty-four patients, 37 males (68.5%), with age (mean±SD) 40.5±10.5 years, were included. The ASQoL global score was 6.8±4.7 (median, 7; range, 0-17). The ASQoL scores had high correlations with physical (rho = 0.79) and mental (0.69) SF-36 components, the SF-36 domains pain (0.82), vitality (0.75), and role-physical (0.68), and the most of the disease-related variables. The ASQoL scores were significantly different between patients with different response levels in the health profile of the EuroQol. The Cronbach́alpha coefficient was 0.86. The reliability had kappa = 1 in 12 items and rho = 0.98. The time spent to complete the ASQoL was from 2 to 5 minutes and there only was a missing answer in one patient. CONCLUSION: The Spanish ASQoL is valid, reliable, and feasible instrument for assessing the HRQL of the AS patients.

[Resource utilization in a cohort of rheumatoid arthritis patients attended in rheumatology units in Spain]. / Utilización de recursos en una cohorte de pacientes con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To determine resource use over a 1-year period in patients with rheumatoid arthritis (RA) attended in rheumatology units in hospitals within the Spanish public health system. PATIENTS AND METHODS: An observational, longitudinal, prospective, multicenter, 1-year study was performed in randomly selected rheumatology units in hospitals of the Spanish public health system. Patients with RA were randomly selected in each hospital. Four visits (at baseline and every 4 months) were conducted by a rheumatologist not routinely involved in the care of the patient. Demographic and disease-related variables were collected. Patient diaries and systematic interviews were used to gather data on resource use. RESULTS: A total of 301 patients were included and 190 (83% females) completed the study. The mean age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The resources most heavily used were medical. All of the patients made medical visits with a median of four visits to rheumatologists (1-13). Ninetynine percent of the patients took at least one drug. The most frequent drugs were paracetamol (41%), deflaza-cort (32%), and methotrexate (24%). Laboratory tests were performed in all patients, and x-rays were performed in 59%. Sixty-one patients (32%) were hospitalized; 75% of these patients were non-surgical. The most frequently used non-medical direct resources were meals and home visits by non-medical staff (39%). Thirtyone patients (16%) had some type of work disability. CONCLUSIONS: AR is associated with substantial utilization of medical and non-medical resources related to the disease and work disability.

[Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain]. / Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. METHODS: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. RESULTS: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59±13 years and the mean disease duration was 10±10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. CONCLUSIONS: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient.

[Rofecoxib versus non-steroidal anti-inflammatory drugs in arthrosis treatment: cost-effectiveness analysis for Spain]. / Rofecoxib frente a antiinflamatorios no esteroideos en el tratamiento de la artrosis: análisis coste-efectividad para España.

OBJECTIVE: Analyze the efficiency of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) versus rofecoxib prescription for arthrosis treatment in Spain through a theoretical model of cost-effectiveness. METHODOLOGY: A theoretical model of decision that evaluates the efficiency of the use of non-selective NSAIDs and rofecoxib in the treatment of patients > 65 years with arthrosis who were nonrespondent to the administration of acetaminophen 4 g/day. The analysis focuses on the estimate of the impact derived from the gastrointestinal (GI) adverse effects. Two alternative analysis contexts are considered: "customary clinical practice" and "rational use of GI drugs" with possible preventive use of gastroprotective (GP) drugs in both groups. The time horizon is 1 year. Direct expenses are estimated from the Spanish Health System perspective. The effectiveness parameter used is the number of severe GI complications prevented. RESULTS: Under the assumptions of the first context, with a 55% estimated combinated prescription of non-selective GP with NSAID, and 6% with rofecoxib, the percentage of cost compensation of rofecoxib is 72%. Under the assumptions of the second context, the cost of rofecoxib is totally compensated when the percentage of combinated prescription of GP with NSAIDs is 59%. CONCLUSION: The use of rofecoxib can be a cost-effective alternative with regard to the traditional non-selective NSAID in the arthrosis treatment, especially in context of higher preventive use of CI drugs.

Purified protein derivative reaction in systemic lupus erythematosus patients. Indirect study of cellular immunity.

Cutaneous anergy in SLE patients results from disease activity and/or immunosuppressive treatment (IT). The aim of this study was to evaluate purified protein derivative (PPD) reaction in SLE patients. A total of 145 patients and 20 controls were studied. Five units of PPD were applied on day 0, and skin reaction was measured after 3 (PPD1) and 6 (PPD2) days. A booster was applied (day 14), and the reaction was measured after 3 (PPD3) and 6 (PPD4) days. Non-parametric ANOVA test and unpaired Student's t-test were performed. Forty patients (group I) were inactive (MexSLEDAI < 3), receiving no IT (at least 3 months previous to the PPD test); 39 (group II) were inactive receiving IT; 24 (group III) were active without IT, and 42 (group IV) were active with IT. Active patients had lower PPD1 (group III, 1.4 +/- 0.9; group IV, 0.6 +/- 0.5) than inactive patients (group I, 8.4 +/- 2.3; group II, 5.1 +/- 1.9) and than controls (9.4 +/- 3; P < or = 0.001). Group IV had lower delayed response (PPD2 = 0.3 +/- 0.3) than inactive groups (group I, 2.6 +/- 0.9; group II, 3.1 +/- 0.8) and than controls (7.9 +/- 2.5; P < or = 0.001). Group III had lower delayed reaction (PPD2 = 1.2 +/- 0.8) than controls (P < or = 0.001). Active SLE patients, receiving or not receiving IT, had lower skin response to PPD than inactive patients and controls.

Development, recurrence, and severity of infections in Mexican patients with rheumatoid arthritis. A nested case-control study.

OBJECTIVE: To determine factors associated with development, recurrence, and severity of infections in patients with rheumatoid arthritis (RA). METHODS: A hospital based nested case-control study in a referral center. The same evaluator reviewed clinical charts of 195 consecutive patients with RA seen in our clinic during 1993. Patients who had had at least one infection were classified as "cases" and the others as "controls." We examined 24 demographic, clinical, therapeutic, and infection related variables. A severity index was developed according to scores provided by 12 independent multidisciplinary evaluators. Recurrent infection was defined as > 2 different infections in the same patient during followup. Descriptive statistics were employed, with comparison between cases and controls by univariate analysis and multiple logistic regression. RESULTS: Two hundred eleven infections were detected in 1274 patient-years (incidence of 0.17 new infections per patient-year). We studied 174 women and 21 men, mean 41 years of age, with a mean duration of symptoms of RA of 5 years. Ninety-five were cases and 100 controls. Cases had longer disease duration before admission and followup (p < 0.05). Infections most commonly seen were upper respiratory tract (n = 74), skin (41), urinary tract (27), and herpes zoster (15). Steroids and/or methotrexate (MTX) were associated in 95% of infections. Infection was associated with duration of RA before admission and followup, comorbidity, extraarticular disease, mean cumulative dose of MTX, time taking steroids, and mean daily dose of D-penicillamine, by univariate analysis. Severity of infection was related to the same variables and years of formal education, and recurrence of infection was related to time of followup and mean dose of MTX and steroids. Multiple logistic regression showed that variables associated with infection were cumulative MTX dose, time taking steroids, and mean daily dose of D-penicillamine. CONCLUSION: Infections were frequent in our RA population. The risk factors associated with infections were the cumulative dose of MTX, duration taking steroids, and mean daily dose of D-penicillamine.