Objective To examine changes in patient reported outcome measures (PROs) over 15 years in a representative population of patients with rheumatoid arthritis (RA), with a particular focus on gender differences. Patients and methods Patients in the Oslo RA register filled in questionnaires including the Modified Health Assessment Questionnaire (MHAQ), the Short-Form 36 (SF-36) with physical (PCS) and mental component summaries and derived utility (SF-6D), visual analogue scales (VAS) for pain, patient global assessment of disease (PtGA) and fatigue, and checklists of medication commonly used in the treatment of RA. Data were collected at five time points during a 15-year period from 1994. Mixed model analyses were used to analyse longitudinal changes in PROs from 1994 to 1996, 2001, 2004 and 2009. Results Data were available from 829–1025 RA patients at each time point. PROs were statistically significantly improved from 1994 to 2009 (MHAQ, SF-36 PCS, SF-6D, pain VAS, PtGA VAS and fatigue VAS; all p<0.001), and also with clinically important improvement. Men reported significantly better health status than women in 1994, but women improved significantly more than men over 15 years with a reduction of the gender gap in 2009. Antirheumatic medication was increasingly used over 15 years with no gender differences. Conclusions RA patients reported statistically significantly improved health status for most PROs from 1994 to 2009. Women improved most, and although they still reported higher disease impact than men, the gender differences were small at the final data collection in 2009.
Significance The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement activation occurs early in COVID-19 patients, and whether this is associated with respiratory failure. This study shows that a number of complement activation products are systemically, consistently, and long-lastingly increased from admission and during the hospital stay. Notably, the terminal sC5b-9 complement complex was associated with respiratory failure. Thus, complement inhibition is an attractive therapeutic approach for treatment of COVD-19.
To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators.The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression.443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts.All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.
Sleep quality is an important aspect of health and well-being and the Outcome Measures in Rheumatology Clinical Trials group has identified sleep quality as a key concern for rheumatoid arthritis (RA) patients1. Patient reported sleep-disturbance is included in the RAID (RA Impact of Disease) score, but not in many other core patient reported outcomes (PROs) and is seldom reported in clinical trials.
Objectives
To assess self-reported sleep disturbance in a large sample of patients from a population based RA registry and identify factors associated with self-reported sleep disturbance.
Methods
In a population based RA registry in Oslo, Norway, 868 patients aged 20-79 years (mean (SD) age 59.9 (12.3) years, disease duration 13.0 (10.8) years, 77.1% females) responded in 2009 to a mailed questionnaire (response rate 60.6%). 844 patients answered the numeric rating scale (NRS) on sleep disturbance due to RA (part of the RAID questionnaire) within the last week, and use of benzodiazepine like sleeping drugs (zopiclone/zolpidem = z-hypnotics) and other medications used in the treatment of RA. Other PROs included 100mm visual analogue scales (VAS) for pain, fatigue and global disease activity (patglob), HAQ (0-3, 3 worst), SF-36 with physical (PCS) and mental (MCS) component scores (0-100, 0=worst), RA Disease Activity Index (RADAI, 0-10, 10 worst) and RAID score (0-10, 10=extreme/very poor). Use of z-hypnotics was significantly associated with MCS, PCS, HAQ, RADAI, RAID, NRS sleep disturbance, VAS pain/fatigue/patglob (all p<0.001), and with disease duration (p=0.03). Linear regression analyses were used to identify factors independently associated with sleep disturbance (0-10 NRS, 10=extreme sleep disturbance) and adjusted for age, gender and disease duration.
Results
Females used z-hypnotics more frequently than males (10.2% vs. 3.5%, p=0.01), but no significant gender differences were seen for age, VAS pain, VAS patglob, MCS, RADAI, or use of sDMARDs, biologics or prednisolone. Adjusted linear regression analyses with sleep disturbance assessed by NRS identified significant associations with gender (B=0.40, 95% CI 0.06, 0.74), HAQ (B=0.40, 95% CI 0.13, 0.67), RADAI (B=0.42, 95% CI 0.27, 0.57) and 10unit increase in VAS pain (B=0.15, 95% CI 0.04, 0.27), VAS fatigue (B=0.18, 95% CI 0.11, 0.25) and MCS (B= -0.51, 95% CI -0.65, -0.38).
Conclusions
Sleep disturbance is to a higher degree reported by females and is independently associated with increased pain, fatigue and worse mental and physical function. Improving sleep quality may reduce RA impact of disease and should be addressed in daily clinical practice when treating patients with RA.
References
Kirwan JR, Newman S, Tugwell PS, Wells GA. Patient Perspective on Outcomes in Rheumatology A Position Paper for OMERACT 9. J Rheumatol 2009;36(9):2067-70.
Joint pain in rheumatoid arthritis (RA) can be reduced by non-steroidal anti-inflammatory drugs (NSAIDs) and selective isoenzyme cyclooxygenase-2 (COX-2) inhibitors (coxibs). All NSAIDs can cause g...
Approximately 10% of patients with rheumatoid arthritis (RA) have coexisting fibromyalgia (FM). Little is known of the cross-sectional and longitudinal relationship between FM and RA disease activity.
Objectives
To examine the cross-sectional and longitudinal relationship between FM and RA disease activity.
Methods
Oslo RA register (ORAR) was established in 1994 as a prospective, observational, longitudinal nested cohort study. The inclusion criteria were RA according to the 1987-ACR classification criteria and a residential address in Oslo. 636 patients in ORAR were asked to participate in a clinical examination in 1999. A trained study-nurse systematically assessed the 18-tender point count and performed 28-tender and 28-swollen joint counts (TJC/SJC). Patients self-reported disease activity and pain related to RA, and completed the Stanford Health Assessment Questionnaire (HAQ). RA disease activity was calculated as DAS28. Fibromyalgia was diagnosed if ≥11 tender points were reported. FM associated variables; fatigue, muscular tenderness, headache, abdominal pain and difficulties concentrating were also scored (0–10 VAS). At the 10-year follow-up patients completed a questionnaire that included RA Disease Activity Index (RADAI) and Routine Assessment of Patient Index Data (RAPID-3). In cross-sectional and longitudinal analyses RA disease activity, FM associated variables and health status were compared between patients with ≥11 and <11 tender points. Level of significance was calculated using ANCOVA models corrected for age, gender, BMI and level of education. The FM associated variables at baseline were also corrected for baseline SJC 28 and C-reactive protein (CRP). The variables in the longitudinal study were corrected for the same variables as the cross-sectional analyses, but additionally for baseline values of the dependent variable when available.
Results
488 patients agreed to participate in the baseline data-collection and 192 participated at the 10-year follow-up. The mean (SD) age was 59.5 (12.5) years, and 87% were female. There were no significant differences in age, disease duration or participation at follow-up between patients with and without FM, but only women had FM. Patients with FM in addition to RA had higher DAS28, SJC, TJC, pain and patient global VAS, but also higher levels of fatigue, abdominal pain and concentration difficulties (table 1). At the 10-year follow-up patient with FM had significantly higher levels of RA disease activity and pain (figure 1).
Conclusions
Presence of FM in patients with RA was associated with significantly higher levels of RA disease activity both in the cross-sectional and longitudinal perspectives. Secondary FM should be considered in patients with RA not reaching remission.
Disease activity and inflammation are established predictors of increased mortality in patients with rheumatoid arthritis (RA).
Objectives
To investigate whether osteoporosis and use of calcium supplementationswere associated with death from cardiovascular disease in RA.
Methods
Patients in the Oslo RA register (ORAR) were examined and BMD measured in 1996. Biomarkers were analysed consecutively. A trained study-nurse recorded patient medication and assessed 28-tender and 28-swollen joint counts. Disease activity was calculated as DAS28. The cohort was linked to the Norwegian Cause of Death registry on Dec 31st, 2010, and we examined all-cause mortality as well as death from cardiovascular disease (Primary cause of death: Acute myocardial infarction, angina, atherosclerotic heart disease, hypertension, cerebral infarction, heart failure or stroke) We analysed all-cause mortality and death from CVD as endpoints in separate Cox regression models with hazard ratio (HR) and 95% confidence intervals (95% CI). Initially, baseline variables were analysed separately, adjusted for age and sex. Variables with a p-value of ≤0.1 were then included into a multivariable model and further excluded using backwards selection with a cut-of p-value of 0.05. Robustness of the final model was assessed by re-entering excluded variables.
Results
609 patients, mean 53.6 years (range 20-70) were examined in 1996/1997. During the period of observation 162 patients had died, while 447 were still alive at time of censoring, 7414 observed patient-years. In 43 (7%) patients CVD was the primary cause of death. Results from the univariate analyses in are presented in the table. In the final multivariate model of all-cause mortality; increased baseline ESR (HR 1.02, 95% CI 1.01-1.03 p<0.001), calcium supplementation (1.68, 1.07-2.62 p=0.02) and osteoporosis (1.56,1.07-2.29 p=0.02) remained associated with higher mortality. In the final multivariate model of death from CVD; increased ESR (1.03, 1.01-1.04 p<0.001) and calcium supplementation (3.03, 1.49-6.15 p=0.002) remained associated with higher mortality.
Conclusions
Increased baseline inflammation and calcium supplementation were associated with increased all-cause mortality and risk of primary atherosclerotic death in this longitudinal study of a representative cohort of RA patients.
Physical inactivity is a major recognized public health challenge. Rheumatoid arthritis (RA) limits physical function, and physical inactivity may contribute to the increased risk of cardiovascular disease in patients with RA. However, limited data are available on the frequency of physical exercise in patients with RA.
Objectives
To assess self-reported physical activity in a large sample of patients from a population based RA registry and explore factors associated with no regular versus regular physical exercise.
Methods
In a population based RA registry in Oslo, Norway, 868 patients aged 20-79 years (mean (SD) age 59.9 (12.3) years, disease duration 13.0 (10.8) years, 77.1% females, 57.0% RF+ or CCP+) responded in 2009 to a mailed questionnaire (response rate 60.6%). 829 patients responded to a question on frequency of physical exercise of at least half an hour with shortness of breath and sweating. Response options were exercise ≥3 times weekly, 1-2 times weekly, 1-2 times monthly, no regular exercise, and none because of reduced function or handicap. Other patient reported outcomes included pain, fatigue and patient reported global disease activity (PatGlob) on 100 mm visual analogue scales, HAQ, SF-36 with physical (PCS) and mental component summary (MCS) (low scores=poor health), SF-6D derived from SF-36 and EQ-5D utility (0-1), Rheumatoid Arthritis Disease Activity Index (RADAI 0-10), Rheumatoid Arthritis Impact of Disease (RAID) score (0-10), and self management on Self-Efficacy Scales (SES 10-100, 100 best).
Results
High level regular activity (≥3 times weekly) and low level regular activity (1-2 times weekly) were reported by 174 (21.0%) patients and 354 (30.6%) patients. Very few patients (N=22, 2.7%) reported some physical activity (1-2 times monthly), while 292 (35.2%) were inactive with no regular exercise, and 87 (10.5%) inactive due to reduced function or handicap. Inactive patients with no regular exercise (45.7%) compared to patients with regular exercise (51.6%) had higher age, longer disease duration, more pain, fatigue, PatGlob, worse physical (HAQ and SF-36 PCS) and mental (SF-36 MCS) function, higher disease activity (RADAI), higher disease impact (RAID), lower utility (SF-6D and EQ-5D), and worse self management scores (all p<0.01). In multivariate logistic regression analyses and with adjustment for age and gender in the final model, years of education (OR 1.20, 95%CI 1.10-1.20), self-efficacy for arthritis symptoms (1.02; 95%CI 1.015-1.025), and physical function SF-36 PCS (OR 1.017, 95%CI 1.002-1.032) were independently associated with regular physical exercise in RA patients.
Conclusions
About half of RA patients are physically inactive, and inactivity is independently associated with worse health status and low levels of self-efficacy and education. Physical activity should be encouraged in patients with RA, especially when these factors associated to inactivity are present, to comply with recommendations for physical exercise to improve quality of life and to prevent cardiovascular morbidity.
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