Complement C3d is not associated with axial spondyloarthritis and magnetic resonance imaging changes at the sacroiliac joint.

OBJECTIVE: To investigate the associations between complement C3d and inflammatory and structural changes by magnetic resonance imaging (MRI) at the sacroiliac joints (SIJ) suggestive of axial spondyloarthritis, according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, in patients with low back pain. METHOD: This was a cross-sectional study of patients referred to the Spine Centre of Southern Denmark owing to unspecified low back pain (Spines of Southern Denmark cohort). The patients were divided into three groups: group 1: patients fulfilling the ASAS criteria for axial spondyloarthritis (axSpA, n = 96); group 2: patients with either a positive MRI of the SIJ and no spondyloarthritis features, or a negative MRI of the SIJ but positive human leucocyte antigen-B27 and one spondyloarthritis feature (non-axSpA, n = 38); group 3: patients with unspecified low back pain for > 3 months (control group, n = 82). Complement C3d was measured with double-decker rocket immunoelectrophoresis and evaluated in relation to the group division and baseline findings by SIJ MRI. RESULTS: In total, 184 C3d analyses were performed. The mean ± sd level of C3d was 33.8 ± 8.1 AU/mL. There were no differences in C3d levels between the three patient groups, mean values being: axSpA = 34.3 ± 7.9 AU/mL, non-axSpA = 33.5 ± 6.9 AU/mL, and controls = 33.4 ± 9.2 AU/mL. The level of C3d was not related to MRI findings. CONCLUSIONS: In these patients, complement C3d was not associated with active or structural SIJ changes on MRI suggestive of axial spondyloarthritis.

Diagnosing axial spondyloarthritis by multidiciplinary team conference at 3.5 years' follow-up in a cohort of patients with disease features according to the ASAS criteria.

OBJECTIVES: During the past two decades, magnetic resonance imaging (MRI) has increasingly been used diagnostically in axial spondyloarthritis (axSpA), and in 2009 MRI was introduced in the Assessment of SpondyloArthritis Society (ASAS) classification criteria. In clinical practice, there is a risk of overdiagnosis if MRI findings are not related to clinical and biochemical findings. The aim of this study was to provide an estimate of the prevalence of axSpA in a cohort of clinical patients with low back pain and findings suggestive of axSpA according to ASAS through consensus diagnosis at a multi-disciplinary team (MDT) conference, and to describe the performance of the features included in the ASAS criteria. METHOD: Consensus diagnoses of axSpA at MDT conferences were retrospectively established at 3.5 years' follow-up in a cohort of 84 patients, initially referred with disease features according to the ASAS criteria. Patients were examined clinically regarding spondyloarthritis features, and biochemical tests and MRI of the sacroiliac joints and entire spine were performed at baseline and after a mean of 3.5 years. RESULTS: According to the MDT consensus, 25 patients (30%) of the total cohort had axSpA at follow-up; 40% of individuals who fulfilled the ASAS criteria at baseline had axSpA, and 37% at follow-up; 96% of axSpA patients according to the MDT consensus met the ASAS criteria at baseline and 92% at follow-up. CONCLUSION: Approximately one-third of the included patients had axSpA when evaluated at the MDT conference. The ASAS criteria had low predictive value, but high sensitivity at both baseline and follow-up.

Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial.

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Factors associated with influenza and pneumococcal vaccine uptake among rheumatoid arthritis patients in Denmark invited to participate in a pneumococcal vaccine trial (Immunovax_RA).

OBJECTIVE: This study investigates predictors of influenza and pneumococcal vaccine coverage among rheumatoid arthritis (RA) patients, and explores possible differences according to type of RA therapy. METHOD: RA patients from two clinics in the region of Southern Denmark were informed about the survey during scheduled follow-up visits. The questionnaire included questions concerning previous influenza and pneumococcal vaccine uptake, attitudes about vaccination, and socio-demographic factors. Factors associated with recalled vaccine uptake were assessed by multivariate logistic regression. RESULTS: A total of 192 RA patients completed the survey, 134 (70%) of whom were women and 90 (47%) were aged ≥ 65 years. Sixty-seven patients (35%) received conventional disease-modifying anti-rheumatic drugs (cDMARDs) and 125 (65%) combination therapy with biological disease-modifying anti-rheumatic drugs (bDMARDs). Self-reported uptake of vaccination against seasonal influenza ever was 59% overall; 57% among patients receiving cDMARDs and 61% in patients receiving bDMARDs. Self-reported vaccine uptake against pneumococcal diseases was only 6% overall. Older age, educational level, and information and recommendation by a specialist or general physician were positively associated with influenza vaccine uptake, while there was no significant difference in vaccine uptake according to RA treatment type. Reasons for not being vaccinated included fear of adverse effects, lack of information and recommendation, and perception of good health. CONCLUSION: We observed a low prevalence of influenza and in particular of pneumococcal vaccinations among RA patients receiving immunosuppressive drugs, with no difference in coverage according to type of RA therapy. More population-specific evidence to support recommendations is required to increase awareness among patients and physicians.

No diagnostic utility of antibody patterns against Klebsiella pneumoniae capsular serotypes in patients with axial spondyloarthritis vs. patients with non-specific low back pain: a cross-sectional study.

OBJECTIVES: To investigate whether antibody response patterns against Klebsiella pneumoniae capsular serotypes can discriminate patients with axial spondyloarthritis (axSpA) from patients with non-specific low back pain (LBP). METHOD: Immunoglobulin (Ig)G and IgA antibodies against K. pneumoniae capsular serotypes K2, K26, K36, and K50 were measured, and antibody seropositivity compared between groups and analysed for patient correlation in five different groups: (a) 96 patients fulfilling the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA; (b) 38 patients with either a positive magnetic resonance imaging (MRI) scan as defined by ASAS or a positive human leucocyte antigen (HLA)-B27 status plus one clinical SpA feature, characterized as 'non-axSpA'; (c) 82 non-specific LBP patients; (d) 40 healthy blood donors and (e) 43 patients with diagnosed ankylosing spondylitis (AS) served as the negative and positive control groups. RESULTS: There was no difference in IgG and IgA seropositivity against all serotypes between the axSpA, non-axSpA, and LBP groups. No significant correlations were found between anti-Klebsiella antibodies and age, gender, HLA-B27, or high-sensitivity C-reactive protein (hsCRP). IgG seropositivity against K50 was more frequent in AS (25.6%) than in axSpA (13.5%, p < 0.05). axSpA patients with radiographic sacroiliitis and AS controls concordantly had the highest frequency of seropositivity for ≥ 2 serotypes (21%). CONCLUSIONS: The antibody patterns against K. pneumoniae serotypes K2, K26, K36, and K50 did not discriminate between early axSpA and non-specific LBP.

The discriminative value of inflammatory back pain in patients with persistent low back pain.

OBJECTIVES: To estimate the prevalence of inflammatory back pain (IBP) characteristics and analyse the discriminative value of IBP relative to axial spondyloarthritis (SpA) according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. METHOD: Patients who had low back pain for > 3 months were selected from a cohort of secondary care patients aged 18-40 years. Data included information on SpA features, human leucocyte antigen (HLA)-B27 typing, C-reactive protein (CRP) level, magnetic resonance imaging (MRI) of the sacroiliac joints, and self-reported IBP questions covering the pain characteristics included in the Calin, Berlin, and ASAS IBP definitions. RESULTS: Of the 759 included patients, 99% [95% confidence interval (CI) 98-100] had at least one IBP characteristic. The prevalence of the single IBP characteristics ranged from 10% (95% CI 7-12) for 'pain worst in the morning' to 79% (95% CI 76-82) for 'morning stiffness'. Two-thirds of the patients (67%, 95% CI 63-70), met at least one of the three IBP definitions. In all, 86 (11%) were classified as 'SpA according to ASAS'. All three IBP definitions were significantly associated with 'SpA according to ASAS'; however, the discriminative value was low, with sensitivity, specificity, and balanced accuracy values of 64, 50, and 57% for Calin, 59, 60, and 60% for Berlin, and 35, 79, and 57% for ASAS IBP definitions, respectively. CONCLUSIONS: In this study population, IBP characteristics were in general common and the discriminative value was low, as IBP could not differentiate patients with SpA according to ASAS criteria from patients with other causes of back pain.

The in-vitro antimicrobial effect of non-antibiotics and putative inhibitors of efflux pumps on Pseudomonas aeruginosa and Staphylococcus aureus.

The anti-microbial activity of six non-antibiotics (one amino-ethylchloride, three phenothiazines, two tricyclic antidepressives) were tested on 20 clinical isolates of Pseudomonas aeruginosa, one clinical isolate of Klebsiella pneumoniae, 2 ATTC strains and 14 clinical isolates of Staphylococccus aureus, using the plate dilution method. The effects on P. aeruginosa were independent of antibiotic resistance pattern and the species Stenotrophomonas maltophilia was found to be the most susceptible to the non-antibiotics, with MIC values as low as 20 mg/l for some of the substances. The 16 S. aureus strains tested were all particularly susceptible to the anti-microbial effects of the putative inhibitors of efflux pumps thioridazine and trifluoperazine with MIC values of < or =16 mg/l independently of the methicillin resistance profile of the strains. Because phenothiazines are well known to inhibit efflux pumps our results may indicate the existence of such pumps. Current works in progress are attempts at reversing the antibiotic resistance of selected bacterial strains using specific non-antibiotics and their stereo-chemical isomers.

[Reactive hyperemia after arterial occlusion: comparison of infrared telethermography and laser Doppler flowmetry]. / Reaktive Hyperämie nach arterieller Okklusion: Vergleich der Infrarot-Tele-Thermographie und der Laser-Doppler-Fluxmetrie.

Before, during and after arterial occlusion we measured Laser-Doppler Flux (LDF) and skin temperature using Infrared-Thermographie (IRT) in 40 healthy adults (20 female, 20 male). In the region of the hypothenar eminence of the left hand LDF and skin temperature showed significantly higher values in male compared with female subjects prior to occlusion (p < 0.01 resp. p < 0.05). After arterial occlusion for 120 seconds LDF showed a significant overshoot of 71.3% (+/- 39.5%) above baseline. During this phase of hyperemia skin temperature rose from 33.5 to 34.8 degrees C (p < 0.0001). This reaction was similar in men and in women. Changes in skin temperature were slower and more prolonged compared with the rapid changes of LDF. The absolute temperatures were significantly higher when we used IRT compared with temperatures measured by resistance thermometry. Both methods showed a close correlation (p < 0.0001, r = 0.891). Using the IRT technique a large number of skin temperatures can be measured simultaneously and temperature changes can be detected and visualized by colour thermograms. Postocclusive cutaneous hyperemia induces similar responses in LDF parameters and in skin temperatures. IRT therefore could be used as an additional tool for the assessment of physiological and pathological functions of the cutaneous microcirculation.

Depression assessed over 1-year survival in patients with myocardial infarction.

OBJECTIVE: To estimate the prevalence of ICD-10 depression using a self-reported questionnaire and to examine if depression is associated with increased 1-year mortality in patients with myocardial infarction (MI). METHOD: In total, 763 MI-patients completed the Major Depression Inventory at discharge. Information from hospital notes was collected and patients were followed 1 year for re-admission and mortality through national registries. RESULTS: Seventy-three patients (9.6%) were depressed at discharge. Depression was not a significant independent predictor of mortality; however, there was a significant trend for increasing mortality with increasing severity of the depressive state (P = 0.028). All mortality among depressed patients was in patients with non-Q-wave infarction. CONCLUSION: Ten per cent of MI-patients fulfilled diagnostic criteria for depression at discharge. There was a significant trend for increasing mortality with increasing severity of the depressive episode. All mortality among depressed patients was seen in patients with non-Q-wave infarction. These findings indicate future studies in selected subgroups of MI-patients.

Psychosocial predictors of depression in patients with acute coronary syndrome.

OBJECTIVE: To describe the prevalence of depression according to ICD-10 criteria using a self-completed questionnaire and to identify psychosocial predictors of depression at discharge in patients with acute coronary syndrome. METHOD: A total of 899 patients with acute coronary syndrome completed the Major Depression Inventory at discharge and a questionnaire regarding previous depression and family history of depression. Information concerning civil status was obtained from the Civil Person Registry. RESULTS: Ninety patients (10%) were depressed according to ICD-10 criteria at discharge with 7.2% having a moderate to severe depression at discharge. Women were significantly more frequently and severely depressed than men. Patients with and without depression reported primarily somatic symptoms of depression. Cardiovascular risk factors or treatment did not differ between patients with and without depression. Previous depression (OR 2.9, 95% CI 1.4-6.0 adjusted) and female gender (OR 2.5, 95% CI 1.5-4.3 adjusted) predicted depression at discharge in a logistic regression model. CONCLUSION: Somatic symptoms of depression are prevalent in patients with acute coronary syndrome. The use of self-completed non-diagnostic questionnaires assessing symptoms of depression therefore is cautioned as patients may wrongly be identified as depressed. In patients with acute coronary syndrome depression is predicted by well-known psychosocial risk factors.