Petter Mowinckel

High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study

Objectives: New effective therapies with particularly good effect on joint destruction have highlighted the need for reliable predictors of radiographic progression in rheumatoid arthritis (RA). Our objective was to assess the combined predictive role of a set of laboratory markers with regard to 10-year radiographic progression, and to examine the effect of anti-cyclic citrullinated peptide (anti-CCP) level. Methods: A cohort of 238 patients with RA was followed longitudinally for 10 years with the collection of clinical data and serum samples. 125 patients with radiographs of the hands available at both baseline and after 10 years were included in this study. Radiographs were scored according to the van der Heijde modified Sharp score. Baseline sera were analysed for C-reactive protein, erythrocyte sedimentation rate (ESR), anti-CCP, IgA rheumatoid factor (RF) and IgM RF. Logistic regression analyses were used to identify predictors of radiographic progression and to examine the effect of anti-CCP level. Results: Anti-CCP (OR 4.0; 95% CI 1.6 to 10.0) was the strongest independent predictor of radiographic progression. Female gender (OR 3.3; 95% CI 1.3 to 7.6), high ESR (OR 3.2; 95% CI 1.2 to 7.6) and a positive IgM RF (OR 3.1; 95% CI 1.2 to 7.9) were also independent predictors. Compared with the anti-CCP-negative patients, patients with low to moderate levels of anti-CCP (OR 2.6; 95% CI 0.9 to 7.2) and patients with high levels of anti-CCP (OR 9.9; 95% CI 2.7 to 36.7) were more likely to develop radiographic progression. Conclusions: Anti-CCP, IgM RF, ESR and female gender were independent predictors of radiographic progression and could be combined into an algorithm for better prediction. Patients with high levels of anti-CCP were especially prone to radiographic progression, indicating that the anti-CCP level may add prognostic information.

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

The comparative one‐year performance of anti–tumor necrosis factor α drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: Results from a longitudinal, observational, multicenter study

OBJECTIVE To compare the 1-year retention rates of anti-tumor necrosis factor alpha (anti-TNFalpha) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status. METHODS Our analyses comprised 847, 172, and 249 anti-TNFalpha treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigators global assessment, and concomitant methotrexate (MTX). Adjusted changes in health-related quality of life (HRQOL) were compared among the groups. RESULTS Unadjusted 1-year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53-1.07) for PsA versus RA and 0.66 (95% CI 0.47-0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA. CONCLUSION Our results suggest that survival of anti-TNFalpha treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.

The prevalence and severity of rheumatoid arthritis in Oslo. Results from a county register and a population survey.

The objective was (1) to examine the prevalence of rheumatoid arthritis (RA) by a county patient register, (2) to cross-validate the register findings by a postal population survey, and (3) to estimate prevalences of disease subsets according to age, sex, and levels of physical disability. The study was performed within a county setting in the city of Oslo with 356,486 inhabitants between 20 and 79 years of age. Prevalence estimates were calculated from a county patient register comprising 1333 patients with RA and a population survey of 10,000 inhabitants. The overall prevalence of RA between 20 and 79 years was 0.437 (95% CI 0.413, 0.461) after adjusting for the incompleteness of the register by a factor of 1.17. Prevalences exceeding 1.0% was only found among females over 60 years. The prevalence of RA with MHAQ scores > or = 1.5 and > or = 2.0 (range 1-4) was 0.225 (95% CI 0.209, 0.243) and 0.099 (0.088, 0.111) respectively. We conclude that RA is less frequent in the city of Oslo than stated in most of the literature. The prevalence of RA with physical disability levels assumed to be associated with increased mortality is less than half of the overall prevalence of 0.4-0.5%.

Activity limitations and participation restrictions in women with hand osteoarthritis: patients’ descriptions and associations between dimensions of functioning

Objective: To describe the functional consequences of hand osteoarthritis, and analyse associations between personal factors, hand impairment, activity limitations, and participation restrictions within the framework of the International Classification of Functioning (ICF). Methods: 87 women with hand osteoarthritis completed a clinical examination including recording of sociodemographic data, measures of hand impairment, and completion of self reported health status measures. The function subscale of the AUSCAN Osteoarthritis Hand Index was used as a measure of hand related activity limitations, while the Canadian Occupational Performance Measure (COPM) was used to describe and measure activity limitations and participation restrictions as perceived by the individual. The study variables were categorised using the dimensions in the ICF framework and analysed using bivariate and multivariate statistical approaches. Results: The patients described problems in many domains of activity and participation. The most frequently described hand related problems were activities requiring considerable grip strength combined with twisting of the hands. On the impairment level, the patients had reduced grip force and joint mobility in the hands, and resisted motion was painful. Regression analyses showed that hand related activity limitations were associated with measures of hand impairment, while activity and participation (as measured by the COPM) were more strongly associated with personal factors than with hand impairment. Conclusions: Hand osteoarthritis has important functional consequences in terms of pain, reduced hand mobility and grip force, activity limitations, and participation restrictions. Rehabilitation programmes should therefore be multidisciplinary and multidimensional, focusing on hand function, occupational performance, and coping strategies.

Validity of physical activity monitors in adults participating in free-living activities

Background For a given subject, time in moderate to very vigorous intensity physical activity (MVPA) varies substantially among physical activity monitors. Objective In the present study, the primary objective, whether time in MVPA recorded with SenseWear Pro2 Armband (Armband; BodyMedia, Pittsburgh, Pennsylvania, USA), ActiGraph (7164, LLC, Fort Walton Beach, Florida, USA), ikcal (Teltronic AG, Biberist, Switzerland) and ActiReg (PreMed AS, Oslo, Norway) is different compared with indirect calorimetry, was determined. The secondary objective, whether these activity monitors estimate energy expenditure differently compared with indirect calorimetry, was also determined. Material and methods The activity monitors and a portable oxygen analyser were worn by 14 men and 6 women for 120 min doing a variety of activities of different intensities. Resting metabolic rate was measured with indirect calorimetry. The cutoff points defining moderate, vigorous and very vigorous intensity were three, six and nine times resting metabolic rate. Results Time in MVPA was overestimated by 2.9% and 2.5% by Armband and ActiGraph, respectively, and was underestimated by 11.6% and 98.7% by ikcal and ActiReg, respectively. ActiReg (p = 0.004) and ActiGraph (p = 0.007) underestimated energy expenditure in MVPA, and all monitors underestimated total energy expenditure (by 5% to 21%). Conclusions Recorded time in MVPA and energy expenditure varies substantially among physical activity monitors. Thus, when comparing physical activity level among studies, it is essential to know the type of physical activity monitor being used.

Asthma drug adherence in a long term clinical trial

AIM To measure drug adherence in children with mild asthma receiving long term prophylactic treatment. METHODS Double blind randomised placebo controlled trial. Patients received inhaled budesonide 100 μg or 200 μg daily, or placebo for 27 months. All participants were asked to inhale medication or placebo from two different Turbuhalers (morning and evening) during the study. A total of 122 children (80 boys, 42 girls) aged 7–16 years with mild asthma (mean FEV1 103.7% of predicted) were included in the trial. Drug adherence was assessed by counting the number of remaining doses in the inhaler when study medication was returned at six month intervals. RESULTS A statistically significant and continuing decrease in measured drug adherence was found from three to nine months and then to 27 months, reaching mean values of 40.6% and 46.9% for inhaled morning and evening medication respectively. Drug adherence declined more rapidly in the placebo group (compared to active treatment); this difference became significant after two years of treatment. Children aged 9 years or less had better drug adherence during the entire study period, but the difference was only significant for the first three months of the study. Measured drug adherence was significantly higher for evening medication compared to morning medication for all study intervals after nine months. CONCLUSION Measured drug adherence diminishes significantly when treating children with mild asthma in a long term trial. This emphasises the importance of monitoring compliance in clinical trials.

Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age

Background: Predicting school-age asthma from obstructive airways disease (OAD) in early life is difficult, even when parental and children’s atopic manifestations are taken into consideration. Objective: To assess if the severity of OAD in the first 2 years of life predicts asthma at 10 years of age. Methods: From a nested case control study within the Environment and Childhood Asthma study, 233 2-year-old subjects with recurrent (⩾2 episodes) bronchial obstruction (rBO+) and 216 subjects without bronchial obstruction (rBO−) underwent clinical examination, parental interview, treadmill test and metacholine bronchial hyperresponsiveness (BHR) measurement at 10 years. A severity score at 2 years was calculated by frequency, persistence of bronchial obstruction and hospital admissions because of OAD. Main outcomes: Current asthma at 10 years (asthma with symptoms and/or asthma medication during the past year and/or positive treadmill test). Secondary outcome was metacholine BHR at 10 years. Results: Compared with rBO− subjects, adjusted odds ratio (95% CI) of current asthma among rBO+ was 7.9 (4.1, 15.3), and among rBO+ with a severity score of >5, 20.2 (9.9, 41.3). In receiver operated characteristic analysis, positive and negative predictive values demonstrated the applicability and value of the score, with an optimal cut-off at severity score 5. Children with severity score >5 had severe BHR more often (PD20 metacholine <1 μmol) than children with a lower or 0 score (p = 0.0041). Conclusion: Using a simple scoring system, a high severity score of OAD by 2 years of age is a strong risk factor for, and may predict, current asthma at 10 years of age.

Consequences of antiepileptic drug withdrawal : A randomized, double-blind study (Akershus Study)

Objective: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health‐related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied.

Body composition in patients with inflammatory bowel disease: a population-based study

OBJECTIVES:Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohns disease (CD) and ulcerative colitis (UC) and to evaluate possible differences between the patient groups and healthy subjects.METHODS:A total of 60 patients with CD, 60 patients with UC, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. Body composition was measured by dual x-ray absorptiometry and Z scores were obtained by comparison to age- and sex-matched normal values.RESULTS:Bone mineral content and lean body mass were significantly lower in patients with CD compared with patients with UC and healthy subjects. The body composition of CD men was more strongly affected than that of women. UC patients had significantly higher fat mass and body mass index than patients with CD and healthy subjects. There was no difference in the percentage of fat mass between the two patient groups. Corticosteroid treatment and smoking had a negative impact on bone mineral content and lean body mass in CD patients independently of each other.CONCLUSIONS:CD was associated with disturbances in body composition: both bone mineral content and lean body mass were significantly reduced, especially in men with CD. Corticosteroid therapy and smoking had a significant influence on body composition in patients with CD. When studying the effects of inflammatory bowel disease on body composition and nutritional status, patients with CD and UC should be evaluated separately.