Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study.

The aim of this study was to investigate (a) the mortality in a clinical cohort of patients with established rheumatoid arthritis in comparison with the general Dutch population over 15 years, (b) the trend in the mortality ratio during the study period, and (c) causes of death and compare these with the general population. In 1997, a sample of 1222 patients was randomly selected from the register of a large rheumatology outpatient clinic. Their mortality and primary causes of death between 1997 and 2012 were obtained from Statistics Netherlands. The standardized mortality ratio (SMR) for all-cause mortality and the number of life-years lost in the study period, adjusted for age, sex, and calendar year, were calculated. A linear poisson regression analysis was performed to evaluate change in all-cause SMR over time. Finally, the SMRs for cause-specific mortality were calculated. The mean age of the population at baseline was 60.4 (SD 15.4) years, and 72.6% of the patients were women. The estimated SMR (95% CI) for all-cause mortality was 1.54 (1.41, 1.67) with about one life-year lost over the study period. There was a trend to decreasing SMR (2% annually, p = .07). Mortality was higher compared with the general population for circulatory system diseases, respiratory system diseases, musculoskeletal system diseases, and digestive system diseases (p < .05). The observed mortality among patients with RA was 54% higher than in the general population after adjustment for age, sex and calendar year. More than one life-year was lost over 15 years, and the mortality tended to decrease over time. The mortality was higher for cardiovascular, respiratory, musculoskeletal and digestive diseases.

Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study.

BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. OBJECTIVE: To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. METHODS: Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. RESULTS: 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0). CONCLUSION: In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.

Association of Somatic Comorbidities and Comorbid Depression With Mortality in Patients With Rheumatoid Arthritis: A 14-Year Prospective Cohort Study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have a significantly increased risk of mortality compared with the general population. One of the most important predictors for mortality is somatic comorbidity. Moreover, studies have demonstrated that comorbid depression is associated with mortality. Which specific comorbidities are associated with mortality is less investigated. The purpose of this study was to investigate the association of a wide range of comorbidities with mortality in patients with RA. METHODS: Longitudinal data over a 14-year period were collected from 882 patients with RA. Data were assessed with questionnaires. The mortality status was obtained from the Statistics Netherlands for the period 1996-2011 for 99% of the patients. Somatic comorbidity was assessed in 1997, 1998, 1999, and 2008 and measured by a national population-based questionnaire including 20 chronic diseases. Comorbid depression was assessed in 1997, 1998, and 1999 and measured with the Center for Epidemiologic Studies Depression Scale. Cox regression was used to study the relationship between comorbidity and mortality. RESULTS: At baseline, 72% of the patients were women. The mean ± SD age was 59.3 ± 14.8 years, and the median (interquartile range) disease duration was 5.0 (2.0-14.0) years. A total of 345 patients died during the study period. Comorbidities that were associated with mortality were circulatory conditions (hazard ratio [HR] 1.60 [95% confidence interval (95% CI) 1.15-2.22]), respiratory conditions (HR 1.43 [95% CI 1.09-1.89]), cancer (HR 2.00 [95% CI 1.28-3.12]), and depression (HR 1.35 [95% CI 1.06-1.72]). CONCLUSION: Comorbid circulatory conditions, respiratory conditions, cancer, and depression are associated with mortality among patients with RA. Careful monitoring of these comorbidities during the course of the disease and adequate referral may improve health outcomes and chances of surviving.

A comparison of the Futuro wrist orthosis with a synthetic ThermoLyn orthosis: utility and clinical effectiveness.

OBJECTIVE: To compare the short-term utility and clinical effectiveness of the commercial-made Futuro wrist orthosis with a newly developed, custom-made ThermoLyn wrist orthosis. METHODS: Using a randomized cross-over trial, 10 patients with rheumatoid arthritis used each of the two orthoses for two weeks. Outcome measures were patients' judgments with respect to different statements about utility and clinical assessments including pain and swelling of the wrist and finger joints, range of motion of the wrist, and grip strength. At the end of the study the patients were asked which of the two orthoses they preferred and why. RESULTS: Patients tended to favor the Futuro wrist orthosis with respect to pain relief and to handling the orthosis. The visual analog scale score of the appearance of the ThermoLyn wrist orthosis was a little higher than that of the Futuro wrist orthosis, but the difference was not statistically significant. Clinical parameters such as pain in the wrist, swelling of the wrist and finger joints, and movements of the wrist showed that the Futuro orthosis tended to be more effective than the ThermoLyn orthosis. None of the differences reached statistical significance. At the end of the study, 5 patients preferred the Futuro and 5 patients the ThermoLyn wrist orthosis. Arguments in favor of the ThermoLyn orthosis were better hygiene, stability, and no need to remove the orthosis during dirty and wet conditions. Arguments in favor of the Futuro orthosis were greater suppleness and freedom of movement. CONCLUSIONS: The ready-made fabric Futuro wrist orthosis appears to be as good as the more expensive individually made synthetic ThermoLyn wrist orthosis with respect to short-term utility and clinical effectiveness. The conditions under which the orthosis will be worn will help to decide which orthosis is the best for the patient. In the event that the patient wants to use the orthosis in wet and dirty conditions, the ThermoLyn wrist orthosis is a good alternative to the Futuro wrist orthosis.

Dialysis associated mucormycosis and desferrioxamine treatment: a case report with review of the role of oxygen radicals.

A hemodialysis patient with pulmonary and cerebral mucormycosis is reported. Recently the occurrence of this infection in dialysis patients has been associated with desferrioxamine (DFO) treatment. A causal relation seems likely, but has not been proved. Several pathogenetic mechanisms are discussed, in particular the influence of DFO on host neutrophil defenses through a decreased oxygen radical production.

[Treatment of rheumatoid arthritis by inhibition of tumor necrosis factor with infliximab or etanercept]. / Behandeling van reumatoïde artritis door blokkade van tumornecrosisfactor met infliximab of etanercept.

The current pharmacotherapy of rheumatoid arthritis (RA) consists of non-steroidal anti inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) such as sulphasalazine, leflunomide and methotrexate. DMARDs can be given as monotherapy or in combination. However, not all patients show an adequate response due to toxicity or lack of efficacy. From animal studies and clinical studies in patients with RA, we know that tumour necrosis factor (TNF) is directly involved in the pathogenesis of RA. Two forms of TNF inhibition therapy have been extensively investigated in RA: anti-TNF monoclonal antibodies (infliximab) and TNF receptor-Fc fusion protein (etanercept). Both types of TNF inhibition induce a rapid improvement in multiple clinical measures of disease activity and patient functional status. Furthermore, a beneficial effect was demonstrated on radiographic progression of joint damage. Etanercept and the combination infliximab-methotrexate are generally well tolerated.

[Generalized side effects with the use of carbamazepine]. / Gegeneraliseerde bijwerkingen bij gebruik van carbamazepine.

Since 1973, 42 cases of generalized adverse reactions to carbamazepine were reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs and the Belgian Centre for Drug Monitoring. The organ involvement can be very diverse in an allergic reaction to carbamazepine. Serious and protracted disturbances in pulmonary diffusion capacity may be present even in the absence of changes on the chest X-ray. Analysis of the type IV mechanism involved suggests that caution is warranted with regard to administration of other drugs during the acute phase of the allergic reaction particularly if these drugs have a propensity to cause type IV allergic reactions themselves.

Long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). METHODS: Longitudinal data over a period of 11 years were collected from 882 patients with RA at study inclusion. Patient-reported outcomes were collected in 1997, 1998, 1999, 2002, and 2008. Physical functioning was measured with the Health Assessment Questionnaire and the physical component summary score of the Short Form 36 health survey. Somatic comorbidity was measured by a questionnaire including 12 chronic diseases. Comorbid depression was measured with the Center for Epidemiologic Studies Depression Scale. We distinguished 4 groups of patients based on comorbidity at baseline. RESULTS: Seventy-two percent of the patients at baseline were women. The mean ± SD age was 59.3 ± 14.8 years and the median disease duration was 5.0 years (interquartile range 2.0-14.0 years). For the total group of patients with RA, physical functioning improved over time. Patients with somatic comorbidity, comorbid depression, or both demonstrated worse physical functioning than patients without comorbidity at all data collection points. Both groups with comorbid depression had the lowest scores. Only patients with both somatic comorbidity and comorbid depression showed significantly less improvement in physical functioning over time. CONCLUSION: Both somatic comorbidity and comorbid depression were negatively associated with physical functioning during an 11-year followup period. Furthermore, their combination seems to be especially detrimental to physical functioning over time. These results emphasize the need to take somatic comorbidity and comorbid depression into account in the screening and treatment of patients with RA.

Quantification of platelet-bound immunoglobulins of different class and subclass using radiolabelled monoclonal antibodies: assay conditions and clinical application.

Quantification of platelet-bound immunoglobulins (PBIg) with radiolabelled murine monoclonal antibodies (mAbs) has been described only for IgG so far. Here we describe some modifications of this mAb radioimmunoassay (MARIA) and show that by using a panel of radiolabelled specific mAbs it is possible to quantify not only PBIgG but also PBIgG subclasses and PBIgM. Analysis by gel filtration showed that all anti-IgG and anti-IgG-subclass mAbs bound to their respective antigens in a ratio of about 1:1. However, the binding ratio for the anti-IgM Mab could not be established. There was a good correlation between the antibody-density per platelet as determined with the anti-IgG mAb and determined as the sum of the IgG molecules of different subclass per platelet (r = 0.90). Platelet fragments did not interfere in the assay. 89 normal healthy controls had 140 IgG molecules per platelet and bound 269 anti-IgM molecules per platelet (geometric means). In a study on the detection of PBIg in 147 thrombocytopenic patients, it appeared that the MARIA had a sensitivity of 61% and a specificity of 45% for the diagnosis of idiopathic thrombocytopenic purpura (ITP). Both in ITP and in secondary thrombocytopenia (STP), PBIgG1 and PBIgG3 were found more frequently (60% and 61%, respectively) than PBIgG2 and PBIgG4 (13% and 9%, respectively). There was no relation between the amount of total PBIgG or PBIgM and the platelet count in either ITP or STP. Also, if IgG antibodies of only one subclass were found, there was no relation between the severity of the thrombocytopenia and the amount of PBIgG. By applying the MARIA, it is possible to quantify PBIgG, all four PBIgG-subclasses and PBIgM in ITP and STP in a reliable way.

The value of a continuous ambulatory activity monitor to quantify the amount and intensity of daily activity in patients with rheumatoid arthritis.

OBJECTIVE: To examine the reliability, validity, and responsiveness of a continuous ambulatory activity monitor in patients with rheumatoid arthritis (RA). METHODS: Forty-one patients with RA, participating in a randomized controlled trial examining the effect of an intensive exercise program, were assessed by means of the Dynaport ADL (activities of daily living) monitor (AM). The time spent on activities (locomotion, standing, and active sitting) during 24 hours and the intensity of trunk movement during these activities were recorded. To determine test-retest reliability 20 patients were reassessed with the AM one week after the first assessment. Construct validity of the AM was determined by comparing the AM results with physical fitness measures (muscle strength, endurance, joint mobility), disease activity, and functional status. As well, 37 patients were assessed 18 months after the first assessment to determine responsiveness. RESULTS: All AM measurements showed satisfactory test-retest reliability (ICC 0.63-0.76). AM measures were significantly associated with physical fitness, functional status, and disease activity, indicating construct validity of the AM. The AM could discriminate between patients with improvement and deterioration in physical fitness, indicating sufficient responsiveness of AM variables. CONCLUSION: This study shows the value of an ambulatory activity monitor to quantify both the amount and intensity of physical activity of patients with RA during a day in their own environment. The ambulatory activity monitor seems to be a promising instrument for research into rehabilitation of patients with RA.

Value of the time trade off method for measuring utilities in patients with rheumatoid arthritis.

OBJECTIVE: To assess the feasibility, reliability, and validity of the time trade off (TTO) in patients with rheumatoid arthritis (RA). METHODS: The TTO was applied in 194 patients with RA with increasing difficulty in performing activities of daily living. The test-retest reliability was determined in 35 of these patients and was calculated by the intraclass correlation coefficient (ICC). Construct validity was evaluated with the following sets of variables: measures of utility (rating scale), quality of life (RAND 36 item Health Status Survey (RAND-36) and RAQoL), functional status (Health Assessment Questionnaire, grip strength, and walk test), and disease activity (doctor's global assessment, disease activity score, pain, and morning stiffness). RESULTS: Ten patients (5%) did not complete the TTO. The median value of the TTO was 0.77 (range 0.03-1. 0). The test-retest ICC of the TTO was 0.85 (p<0.001). Construct validity testing of the TTO showed poor to moderate correlations (Spearman's r(s) between 0.19 and 0.36, p<0.01) with all outcome measures except for the subscale role limitation (physical problem) of the RAND-36, the walk test, the doctor's global assessment of disease activity, and morning stiffness. Multiple regression analysis showed that only 17% of the variance of the TTO scores could be explained. CONCLUSIONS: The TTO method appeared to be feasible and reliable in patients with RA. The poor to moderate correlations of the TTO with measures of quality of life, functional ability, and disease activity suggest that the TTO considers additional attributes of health status. This may have implications for the application of the TTO in clinical trials in patients with RA.

Cost effectiveness and cost utility analysis of multidisciplinary care in patients with rheumatoid arthritis: a randomised comparison of clinical nurse specialist care, inpatient team care, and day patient team care.

OBJECTIVE: To assess the relative cost effectiveness of clinical nurse specialist care, inpatient team care, and day patient team care. METHODS: Incremental cost effectiveness analysis and cost utility analysis, alongside a prospective randomised controlled trial with two year follow up. Included were patients with rheumatoid arthritis (RA) with increasing difficulty in performing activities of daily living over the previous six weeks. Quality of life and utility were assessed by the Rheumatoid Arthritis Quality of Life questionnaire, the Short Form-6D, a transformed rating scale, and the time tradeoff. A cost-price analysis was conducted to estimate the costs of inpatient and day patient hospitalisations. Other healthcare and non-healthcare costs were estimated from cost questionnaires. RESULTS: 210 patients with RA (75% female, median age 59 years) were included. Aggregated over the two year follow up period, no significant differences were found on the quality of life and utility instruments. The costs of the initial treatment were estimated at euro 200 for clinical nurse specialist care, euro 5000 for inpatient team care, and euro 4100 for day patient team care. Other healthcare costs and non-healthcare costs were not significantly different. The total societal costs did not differ significantly between inpatients and day patients, but were significantly lower for the clinical nurse specialist patients by at least euro 5400. CONCLUSIONS: Compared with inpatient and day patient team care, clinical nurse specialist care was shown to provide equivalent quality of life and utility, at lower costs. Therefore, for patients with health conditions that allow for any of the three types of care, the preferred treatment from a health-economic perspective is the care provided by the clinical nurse specialist.

Alpha- and gamma-tocopherol in plasma, red blood cells, and platelets during plasma exchange.

The effect of a rapid reduction of plasma lipoproteins on the alpha- and gamma-tocopherol levels in plasma, erythrocytes, and platelets was studied. Sixteen successive plasma exchange procedures performed weekly in an adult with heterozygous familial hypercholesterolemia were evaluated. Plasma exchange was done by intermittent flow centrifugation, exchanging one plasma volume against a 4% human albumin solution. Plasma exchange reduced in plasma alpha-tocopherol from 41.5 +/- 8.9 to 23.6 +/- 4.8 mumol/L and gamma-tocopherol from 4.9 +/- 4.1 to 2.4 +/- 2.1 mumol/L, without changing their ratios to total lipids. It diminished alpha-tocopherol in platelets from 12.97 +/- 4.37 to 10.03 +/- 1.78 mumol/10(13) cells and gamma-tocopherol from 1.43 +/- 0.55 to 1.06 +/- 0.41 mumol/10(13) cells, but did not affect erythrocyte tocopherols. The total amount removed per procedure was 47.57 +/- 13.65 mumol for alpha-tocopherol and 4.70 +/- 3.59 mumol for gamma-tocopherol. Plasma exchange increased the number of erythrocytes from 3.67 +/- 0.10.10(12) to 4.05 +/- 0.13.10(12) cells/L, without affecting their volume. Platelet count did not change, but mean platelet volume decreased from 7.7 +/- 0.5 to 6.9 +/- 0.5 fl and platelet distribution width from 15.1 +/- 0.4 to 14.9 +/- 0.5. Thus, plasma exchange reduces plasma alpha- and gamma-tocopherol to the same extent as total lipids, and decreases these tocopherols in circulating platelets, along with a reduction in platelet size and, compared to the change in erythrocyte count, a fall of platelet number.(ABSTRACT TRUNCATED AT 250 WORDS)

The validity of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire.

OBJECTIVE: To examine further the usefulness of a 30-item disease-specific quality of life (QoL) questionnaire in patients with rheumatoid arthritis (RA). METHODS: The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire was applied to two groups consisting of 210 and 300 patients with RA, one group with increasing difficulty in performing activities of daily living and one group with stable disease. The associations between the RAQoL and measures of utility, QoL, functional status and disease activity were evaluated. Factor analysis was carried out to investigate if one or more QoL dimensions could be distinguished within this questionnaire. RESULTS: Similar results regarding the association between the RAQoL and different sets of outcome measures were found in the two groups of patients. Regression analysis showed that about 75% of the variance of the RAQoL could be explained with variables of QoL, functional status and disease activity. Physical contact could be distinguished as a separate dimension within the RAQoL, in addition to the dimensions mobility/energy, self-care and mood/emotion. CONCLUSION: The RAQoL is a valid instrument for measuring QoL in different populations of patients with RA. Physical contact, a dimension that is not covered by other common instruments in RA, could be distinguished as a separate dimension within the questionnaire.