Does residential exposure to air pollutants influence mortality and cardiovascular morbidity of older people from primary care?

BACKGROUND: Diseases affecting the cardiovascular system are the most common cause of death worldwide. In addition to classical risk factors of atherosclerosis, long-term exposure to particulate matter with particles of size up to 10 µm (PM10) in the atmosphere has become an increasing focus of scientific attention in recent decades. This study analyses the associations of residential-associated air pollutants exposure with all-cause mortality and cardiovascular morbidity of older patients in a primary care setting. METHODS: The "German Epidemiological Trial on Ankle Brachial Index" (getABI) is a prospective cohort study that started in 2001 and included 6,880 primary care patients with a follow-up of 7 years. The PM10 and nitrogen dioxide (NO2) concentrations in the atmosphere are interpolated values from the study "Mapping of background air pollution at a fine spatial scale across the European Union". The primary outcome in this analysis is death of any cause, a secondary outcome is onset of PAD. Cox proportional hazards regression was used in a two-step modelling, the first step with basic adjustment only for age, sex, and one or more air pollutants, the second with additional risk factors. RESULTS: A total of 6,819 getABI patients were included in this analysis. 1,243 of them died during the study period. The hazard ratio (HR) (1.218, 95%-confidence-interval (CI) 0.949-1.562) for the risk of death from any cause was elevated by 22% per 10 µg/m3 increase of PM10 in the fully adjusted model, although not statistically significant. Increased PM10 exposure in combination with the presence of PAD had a significantly increased risk (HR = 1.560, 95%-CI: 1.059-2.298) for this endpoint in the basic adjustment, but not in the fully adjusted model. 736 patients developed peripheral artery disease (PAD) during the course of the study. There was no association of air pollutants and the onset of PAD. CONCLUSIONS: Our analysis renders some hints for the impact of air pollutants (PM10, NO2, and proximity to major road) on mortality. Interaction of PAD with PM10 was found. There was no association of air pollutants and the onset of PAD. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00029733 (19/09/2022).

Potentially inappropriate medication including drug-drug interaction and the risk of frequent falling, hospital admission, and death in older adults - results of a large cohort study (getABI).

Introduction: With growing age, multiple chronic diseases may result in polypharmacy. Drugs that should be avoided in older adults are called potentially inappropriate medications (PIM). Beyond PIM, drug-drug interactions (DDI) are known to be related to adverse drug events. This analysis examines the risk of frequent falling, hospital admission, and death in older adults associated with PIM and/or DDI (PIM/DDI) prescription. Materials and methods: This post hoc analysis used data of a subgroup of the getABI study participants, a large cohort of community-dwelling older adults. The subgroup comprised 2120 participants who provided a detailed medication report by telephone interview at the 5-year getABI follow-up. The risks of frequent falling, hospital admission, and death in the course of the following 2 years were analysed by logistic regression in uni- and multivariable models with adjustment for established risk factors. Results: Data of all 2,120 participants was available for the analysis of the endpoint death, of 1,799 participants for hospital admission, and of 1,349 participants for frequent falling. The multivariable models showed an association of PIM/DDI prescription with frequent falling (odds ratio (OR) 1.66, 95% confidence interval (CI) 1.06-2.60, p = 0.027) as well as with hospital admission (OR 1.29, 95% CI 1.04-1.58, p = 0.018), but not with death (OR 1.00, 95% CI 0.58-1.72, p = 0.999). Conclusion: PIM/DDI prescription was associated with the risk of hospital admission and frequent falling. No association was found with death by 2 years. This result should alert physicians to provide a closer look at PIM/DDI prescriptions.

A systematic comparison of different composite measures (DAS 28, CDAI, SDAI, and Boolean approach) for determining treatment effects on low disease activity and remission in rheumatoid arthritis.

BACKGROUND: Some composite measures for determining the treatment effects of disease-modifying antirheumatic drugs on remission and low disease activity (LDA) in rheumatoid arthritis (RA) may produce misleading results if they include an acute phase reactant (APR). To inform the choice of appropriate measure, we performed a systematic comparison of treatment effects using different composite measures. METHODS: We used data generated for a systematic review of biologics in RA conducted by the Institute for Quality and Efficiency in Health Care and data from systematic reviews of newer biologics and Janus kinase (JAK) inhibitors provided by sponsors. The studies included had been conducted up to 2020 and investigated comparisons of biologics with placebo and head-to-head comparisons of biologics. Treatment effects on LDA and remission in studies investigating biologics or JAK inhibitors in RA were compared among 4 composite measures: the disease activity score 28 (DAS 28), the simplified disease activity index (SDAI), the Boolean approach (remission only), and the clinical disease activity index (CDAI)-only the latter does not include an APR. RESULTS: 49 placebo-controlled studies included 9 different biologics; 48 studies (16,233 patients) investigated LDA and 49 (16,338 patients) investigated remission. 11 active-controlled studies (5996 patients) investigated both LDA and remission and included 5 different head-to-head comparisons of biologics and 5 different comparisons (6 studies) of biologics with JAK inhibitors. Statistically significantly larger treatment effects were found for biologics or JAK inhibitors versus placebo or active control in 16% of pairwise comparisons of composite measures (27 of 168). Most of these larger effects were observed for composite measures with an APR, i.e. the DAS 28 (19 comparisons) followed by the SDAI (n = 7). Larger effects were most frequently detected in favour of interleukin (IL)-6 inhibitors and to a lesser extent for JAK inhibitors versus treatments with different modes of action. CONCLUSIONS: The use of the DAS 28 and SDAI in clinical studies may generate results favouring certain treatments based on their mode of action (e.g. IL-6 inhibitors versus other biologics). To enable unbiased comparative effectiveness research, a composite measure without an APR (i.e. the CDAI) should thus be the measure of choice.

[Positive experiences of specialist assistants and physicians with respect to the delegation research project StaerkeR : Evaluation of the training and experiences within the framework of this project]. / Positive Erfahrungen von Fachassistent:innen und Ärzt:innen hinsichtlich des Delegations-Forschungsprojekts StärkeR : Evaluation der Schulung und Erfahrungen im Rahmen dieses Projekts.

INTRODUCTION: The delegation of medical services to rheumatology assistants (RFA) has proven to be safe and effective in the evaluation of the research project "StaerkeR". Afterwards, the experiences of the participating RFAs and rheumatologists with delegation were surveyed and discussed within the framework of an opinion research project. METHODS: At the end of the project, the participating RFAs and rheumatologists were surveyed via an online questionnaire (quantitative analysis) (21 questions for physicians and 44 questions for RFAs). In addition, focus group meetings were held for the RFAs, which were led by a moderator and a secretary. The results of the focus group sessions (qualitative analyses) were analyzed according to the structured method of Kuckartz. RESULTS: All 31 RFAs and 25 rheumatologists involved in the project participated in the online surveys and 9 RFAs took part in the 2 focus groups. In the online surveys, both the RFAs and the rheumatologists gave predominantly good to very good ratings with respect to RFA training, the implementation of delegation in the practices and outpatient clinics, the role of the RFAs and the overall evaluation of the delegation concept. In the focus group discussions, many possible limitations regarding acceptance and implementation of the delegation concept were mentioned. CONCLUSION: The delegation of medical tasks to RFAs is a concept that is positively assessed and highly accepted by both sides, the rheumatologists and the RFAs. In a comparison between the individual practices and hospital outpatient departments, there is still a clear heterogeneity with respect to the willingness and logistical possibilities in the implementation of the delegation concept.

The Efficacy of Short-Term Bridging Strategies With High- and Low-Dose Prednisolone on Radiographic and Clinical Outcomes in Active Early Rheumatoid Arthritis: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. This study was undertaken to compare the effect of 3 bridging strategies, including high-dose and low-dose prednisolone, on radiographic and clinical outcomes. METHODS: Adult RA patients from 1 rheumatology hospital and 23 rheumatology practices who presented with moderate/high disease activity were randomized (1:1:1) to receive 60 mg prednisolone (high-dose prednisolone [HDP]) or 10 mg prednisolone (low-dose prednisolone [LDP]) daily (tapered to 0 mg within 12 weeks) or placebo. The 12-week intervention period was followed by 40 weeks of therapy at the physicians' discretion. The primary outcome measure was radiographic change at 1 year measured using the total modified Sharp/van der Heijde score (SHS). Disease activity was assessed with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). RESULTS: Of 395 randomized patients (HDP, n = 132; LDP, n = 131; placebo, n = 132), 375 (95%) remained in the modified intention-to-treat analysis. Mean ± SD changes in SHS scores in the 3 groups after 1 year were comparable: mean ± SD 1.0 ± 2.0 units in the HDP group, 1.1 ± 2.2 units in the LDP group, and 1.1 ± 1.5 units in the placebo group. The primary analysis showed no superiority of HDP compared to placebo (estimated difference of the mean change -0.04 [95% confidence interval (95% CI) -0.5, 0.4]). At week 12, the mean DAS28-ESR differed: -0.6 (95% CI -1.0, -0.2) for HDP versus placebo; -0.8 (95% CI -1.2, -0.5) for LDP versus placebo. At week 52, there was no significant difference in DAS28-ESR between the 3 groups (range 2.6-2.8). Serious adverse events occurred similarly often. CONCLUSION: Short-term glucocorticoid bridging therapy at a high dose showed no benefit with regard to progression of radiographic damage at 1 year.

The Structured Delegation of Medical Care Services for Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: In some areas of Germany, there is a shortage of specialist physicians for patients with inflammatory rheumatic diseases. Delegating certain medical care services to qualified, specialized rheumatological assistants (SRAs) might be an effective way to supplement the available capacity for specialized medical care. METHODS: Patients under stable treatment for rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were included in this trial, which was designed to demonstrate, in a first step, the non-inferiority of a form of care involving delegation of physicians' tasks to SRAs (team-based care), in comparison to standard care, with respect to changes in disease activity at one year. "Non-inferiority," in this context, means either superiority or else an irrelevant extent of inferiority. In a second step, in case non-inferiority could be shown, the superiority of team-based care with respect to changes in patients' health-related quality of life would be tested as well. Disease activity was measured with the Disease Activity Score 28, and health-related quality of life with the EQ-5D-5L. This was a randomized, multicenter, rater-blinded trial with two treatment arms (team-based care and standard care). The statistical analysis was performed with mixed linear models (DRKS00015526). RESULTS: From September 2018 to June 2019, 601 patients from 14 rheumatological practices and 3 outpatient rheumatological clinics in the German states of North Rhine-Westphalia and Lower Saxony were randomized to either team-based or standard care. Team-based care was found to be non-inferior to standard care with respect to changes in disease activity (adjusted difference = -0.19; 95% confidence interval [-0.36; -0.02]; p <0.001 for non-inferiority). Superiority with respect to health-related quality of life was not demonstrated (adjusted difference = 0.02 [-0.02; 0.05], p = 0.285). CONCLUSION: Team-based care, with greater integration of SRAs, is just as good as standard care in important respects. Trained SRAs can effectively support rheumatologists in the care of stable patients with RA or PsA.

Reduction of Potentially Inappropriate Medication in the Elderly.

BACKGROUND: Medications with an unfavorable risk-benefit profile in the elderly, and for which there are safer alternatives, are designated as potentially inappropriate medications (PIM). The RIME trial (Reduction of Potentially Inappropriate Medication in the Elderly) was based on PRISCUS, a list of PIM that was developed in 2010 for the German pharmaceuticals market. In this trial, it was studied whether special training and the PRISCUS card could lessen PIM and undesired drug-drug interactions (DDI) among elderly patients in primary care. METHODS: A three-armed, cluster-randomized, controlled trial was carried out in two regions of Germany. 137 primary care practices were randomized in equal numbers to one of two intervention groups-in which either the primary care physicians alone or the entire practice team received special training-or to a control group with general instructions about medication. The primary endpoint was the percentage of patients with at least one PIM or DDI (PIM/DDI) per practice. The primary hypothesis was that at 1 year this endpoint would be more effectively lowered in the intervention groups compared to the control group. RESULTS: Among 1138 patients regularly taking more than five drugs, 453 (39.8%) had at least one PIM/DDI at the beginning of the trial. The percent - ages of PIM/DDI at the beginning of the trial and 1 year later were 43.0% and 41.3% in the intervention groups and 37.0% and 37.6% in the control group. The estimated intervention effect of any intervention (69 practices) versus control (68 practices) was 2.3% (p = 0.36), while that of team training (35 practices) versus physician training (34 practices) was 4.3% (p = 0.22). CONCLUSION: The interventions in the RIME trial did not significantly lower the percentage of patients with PIM or DDI.

Effects of Three Different Methods Defining Onset of Peripheral Artery Disease on the Assessments of Incidence and Important Predictors - Results from the German Epidemiological Trial on Ankle Brachial Index (getABI).

PURPOSE: The common definition of asymptomatic peripheral artery disease (PAD) by a single determination of the ankle brachial index (ABI) has some uncertainty due to measurement errors. This may impact estimates of PAD incidence and assessment of PAD risk factors. To investigate this issue, we used three methods to define asymptomatic PAD and made use of data from the German Epidemiological Trial on Ankle Brachial Index (getABI). PATIENTS AND METHODS: A total of 6,880 unselected subjects aged ≥65 years, enrolled by 344 trained general practitioners, had ABI assessments at baseline and four visits during follow-up. The first approach defined asymptomatic PAD onset as soon as a single ABI value was below 0.9 (single ABI). The second approach employed a regression method using all available ABI values (regression A), while for the third approach (regression B), an extended regression beyond the last valid ABI value for the observation time of the study was allowed. For each approach, we calculated PAD incidence rates and assessed the effect of important PAD predictors using multivariable Cox proportional hazards regression. RESULTS: The regression method A showed the lowest (25.0 events per 1,000 person years) and the single ABI method the highest incidence rate (41.2). The regression methods assigned greater impact to several risk factors of incident PAD. Using regression A, the hazard ratios (HR) of active smoking (2.36; 95% CI 1.92 to 2.90) and of diabetes (1.33; 95% CI 1.13 to 1.56), using regression B the HR of older age (1.72; 95% CI 1.50 to 1.97) were about twice as high as the corresponding HR of the single ABI approach. CONCLUSION: Use of the single ABI method leads to higher PAD incidence rates and to lower impact of important PAD predictors compared to regression methods. For an alert risk factor management, multiple ABI determination may be useful.

Socioeconomic factors and the onset of peripheral artery disease in older adults.

Background: As evidence concerning the impact of socioeconomic factors on the risk of peripheral artery disease (PAD) is sparse, we assessed the association of education and area-level factors (population density, type of municipality and local unemployment rate) on the onset of PAD in older adults. Patients and methods: The analysis used data of the getABI study, a prospective cohort study with seven years of follow-up. Onset of PAD was determined by ankle brachial index (<0.9) or PAD symptoms. Cox regression analysis was employed. Results: Out of 5,444 primary care attendees without PAD at baseline, there were 1,381 participants with PAD onset (cumulative observation time 31,739 years), yielding an event rate of 43.5 (0.95 confidence interval [0.95 CI] 41.2-45.8) per 1,000 person-years. Multivariable Cox regression analysis showed an association of PAD onset with low education (hazard ratio 1.29; 0.95 CI 1.14-1.46; P<0.001), high population density (0.93; 0.89-0.98; P=0.002), small cities (compared to large cities) (0.71; 0.53-0.96; P=0.027) and high local unemployment rate (1.04; 1.00-1.07; P=0.032). The impact of low education on PAD onset was higher for men (2.11; 1.64-2.72) than for women (1.22; 1.07-1.40) (interaction term P=0.013). Conclusions: Socioeconomic factors, education as well as area-level socioeconomic indicators, make independent contributions to PAD onset in older adults.

Dose tapering of biologic agents in patients with rheumatoid arthritis-results from a cohort study in Germany.

OBJECTIVE: To assess the association of demographic and clinical factors with the clinical decision of tapering biologic disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) in daily practice. METHODS: All RA patients receiving bDMARDs were documented by 14 rheumatologists when presenting in 9 specialized private practices. Statistical analyses employed multivariable logistic models for dose reduction with the covariates age, gender, disease duration until bDMARD start, smoking status, disease activity, comorbidity, functional capacity, radiographic damage, concomitant methotrexate (MTX) treatment, rheumatoid factor positivity, and glucocorticoid use. In the multivariable model (MVM), missing values were imputed. RESULTS: Data of 586 RA patients on bDMARD treatment were available, 171 of which (29%) received a reduced dose. The highest rates of patients with dose reduction were seen for rituximab (67%) and infliximab (50%). The degree of dose reduction was most prominent for rituximab (57%). In the MVM, 6/11 covariates were significantly associated with dose reduction: age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.05; P = 0.002), time between disease onset and bDMARD start (OR 1.03, 95% CI 1.01-1.06; P = 0.015), DAS 28 < 2.6 (OR 1.55, 95% CI 1.01-2.37; P = 0.045), MTX therapy (OR 1.52, 95% CI 1.03-2.25; P = 0.036), comorbidity (OR 1.20, 95% CI 1.01-1.42; P = 0.036), and glucocorticoid dose (OR 0.82, 95% CI 0.76-0.89; P < 0.001). CONCLUSION: DAS 28 remission, concomitant MTX, and lower glucocorticoid doses were positively associated with dose tapering of bDMARDs in RA patients. While this could be expected, the reason for the association with age, comorbidity, and the time between disease onset and bDMARD start is less clear. Key points • In rheumatology practice, tapering of biologic disease modifying antirheumatic drugs is feasible in nearly 30% of patients with rheumatoid arthritis. • The degree of dose reduction may exceed 50% of the recommended dose. • In a multivariable model, concomitant methotrexate is positively associated with dose tapering of biologic disease modifying antirheumatic drugs.

Comparative effectiveness of biological medicines in rheumatoid arthritis: systematic review and network meta-analysis including aggregate results from reanalysed individual patient data.

OBJECTIVE: To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes. DESIGN: Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data. DATA SOURCES: Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks. RESULTS: 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included. CONCLUSIONS: For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.

Gamma-glutamyl transferase as a risk factor for mortality and cardiovascular events in older adults - results from a prospective cohort study in a primary care setting (getABI).

Background: In primary care, the gamma-glutamyl transferase (GGT) activity is used for assessing hepatobiliary dysfunction, but is also known to be associated with the risk of cardiovascular events as well as overall mortality. As this knowledge is mainly based on cohorts with middle-aged participants, we aim to assess these associations in elderly patients in a primary care setting. Patients and methods: 6,880 unselected primary care patients, aged 65 years or older, were enrolled by 344 general practitioners all over Germany (getABI study). During seven years of follow-up, coronary heart disease (CHD) events (myocardial infarction or coronary revascularization), cerebrovascular events (stroke or carotid revascularization) and deaths were recorded. Event rates were calculated and Cox regression analysis with adjustment for age, gender, GGT, classical and other risk factors (e.g. education, homocysteine, C-reactive protein, vitamin D) was performed. Results: 1,243 patients died. 27.8 deaths per 1,000 patient years (0.95 confidence interval [0.95 CI]: 26.2-29.3) occurred in the whole cohort. 605 participants had a CHD event, i.e. 16.1 per 1,000 patient years (0.95 CI: 14.8-17.4). 296 cerebrovascular events were observed, i.e. 7.7 per 1,000 patient years (0.95 CI: 6.9-8.6). Cox regression analysis with adjustment for the above-mentioned risk factors showed a significant impact of baseline elevation of GGT above the 3rd quartile (women > 18 U/L, men > 26 U/L) compared to the rest on mortality (hazard ratio [HR] 1.38, 95% CI 1.22-1.56, p < 0.001) and cerebrovascular events (1.39, 95% CI: 1.08-1.79), p = 0.010), whereas the association with CHD events (HR: 1.16, 95% CI: 0.97-1.39, p = 0.103) showed no significance. Conclusions: In a primary care setting, GGT values have a significant association with overall mortality and cerebrovascular events, but not with CHD events in elderly patients.

Nurse-led care versus physician-led care in the management of rheumatoid arthritis and psoriatic arthritis (StaerkeR): study protocol for a multi-center randomized controlled trial.

BACKGROUND: In Germany, the care of patients with inflammatory arthritis could be improved. Although specialized rheumatology nurses could take over substantial aspects of patient care, this hardly occurs in Germany. Thus, the aim of the study is to examine structured nursing consultation in rheumatology practices. METHODS/DESIGN: In total, 800 patients with a stable course of rheumatoid arthritis or psoriatic arthritis in 20 centers in North Rhine-Westphalia and Lower Saxony will be randomized to either nurse-led care or standard care. Participating nurses will study for a special qualification in rheumatology and trial-specific issues. It is hypothesized that nurse-led care is non-inferior to standard care provided by rheumatologists with regard to a reduction of disease activity (DAS28) while it is hypothesized to be superior regarding changes in health-related quality of life (EQ-5D-5L) after 1 year. Secondary outcomes include functional capacity, patient satisfaction with treatment, and resource consumption. DISCUSSION: Since there is insufficient care of rheumatology patients in Germany, the study may be able to suggest improvements. Nurse-led care has the potential to provide more efficient and effective patient care. This includes a more stringent implementation of the treat-to-target concept, which may lead to a higher percentage of patients reaching their treatment targets, thereby improving patient-related outcomes, such as quality of life, functional capacity, and participation. Additionally, nurse-led care may be highly cost-effective. Finally, this project may form the basis for a sustainable implementation of nurse-led care in standard rheumatology care in Germany. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00015526. Registered on 11 January 2019.

Patients with fibromyalgia rarely fulfil classification criteria for axial spondyloarthritis.

Background: The Assessments of Spondyloarthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) have been criticized because of insufficient differentiation towards FM. The aim of this study was to compare the performance of currently used classification criteria in patients diagnosed with axSpA or FM. Methods: Patients were prospectively included if diagnosed with axSpA or FM by the treating rheumatologist and evaluated by an independent examiner for fulfilment of the classification criteria for axSpA (ASAS criteria) and/or FM (1990 ACR classification and 2010 ACR diagnostic criteria). Patients with axSpA were stratified based on classification as non-radiographic axSpA (nr-axSpA) or AS. Symptom severity was assessed by established disease-related questionnaires. Results: Overall, 300 patients were included, 100 with FM and 200 with axSpA of which 100 each had nr-axSpA and AS. Almost all FM patients fulfilled the 2010 (100%) and 1990 ACR criteria (98%) for FM, but only 2% fulfilled the ASAS criteria. When calculations were based on only the FM patients with available HLA-B27 results (n = 40), the proportion fulfilling the ASAS criteria was 5%. All axSpA patients met the ASAS criteria but also the 2010 (24%) and 1990 (13.5%) FM criteria. More patients with AS (29% and 19%) than with nr-axSpA (19% and 8%) fulfilled the 2010 and 1990 FM criteria, respectively. Conclusion: FM patients only rarely fulfil classification criteria for axSpA but some axSpA patients also fulfil FM criteria. Since this was more frequent in patients with AS it may be related to the severity and duration of chronic pain in axSpA patients. Assessment instruments evaluated in axSpA are not disease-specific. The phenomenon of central pain sensitization in rheumatic diseases deserves more study.

Diagnostic value of a 3-day course of prednisolone in patients with possible rheumatoid arthritis - the TryCort study.

BACKGROUND: In patients with tender and swollen finger joints, the differential diagnosis between rheumatoid arthritis (RA) and osteoarthritis (OA) of the hands can be initially difficult. This prospective study (the TryCort study) was performed to study the diagnostic value of prednisolone in differentiating between RA and hand OA. We present the results of this potentially diagnostic test in patients with possible RA in daily clinical practice by demonstrating the results of a pilot and a validation part of this 'prednisolone test' (pred-test). METHODS: We investigated the response to a 3-day course of 20 mg of prednisolone in patients with suspicion of RA. All patients received 1 g of paracetamol per day for 5 days for pain relief. On days 3-5, a morning dose of 20 mg of prednisolone was added. Hand pain was quantified on a 0-10 Numerical Rating Scale, and the subjective percentage of improvement (0-100%) was recorded. Thresholds for response to prednisolone were investigated in a pilot phase with differentiation in response between patients with RA and patients with OA of the hands, both with pain in the hands ≥4. In a validation phase, the best differentiating cut-off of the pilot phase was applied to discriminate responders from non-responders in consecutive patients with hand pain ≥4 referred because of suspected RA. Final diagnoses were made by the expert upon re-examination at week 12. Primary outcomes were the sensitivity and specificity of a positive test in relation to the diagnosis. RESULTS: A percentage of 40% subjective improvement of pain in the hands on day 3 discriminated best between RA and OA in the pilot phase. Among 95 patients with complete data in the validation phase, RA was diagnosed in about 50%. Patients with RA had more swollen joints, higher C-reactive protein levels and slightly higher Health Assessment Questionnaire scores. The pred-test was positive in 42.1% of all patients (40 of 95). The median percentage of improvement on day 5 was higher in RA than in non-RA: 50% (IQR 30-60%) vs. 20% (IQR 10-30%) (p < 0.001). The sensitivity and specificity of the pred-test were 0.6 (95% CI 0.5-0.8) and 0.8 (95% CI 0.7-0.9), respectively, and the positive and negative predictive values were 0.77 and 0.70, respectively. CONCLUSIONS: To our knowledge, this is the first evaluation of the widely used pred-test that has ever been performed. The pred-test had a moderate sensitivity and a good specificity. We conclude that rheumatologists may use this test in unclear clinical situations to better differentiate between inflammatory and other conditions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01395251 . Registered on 14 Jul 2011. EudraCT number: 2011-002633-19. Registered on 21 Dec 2011.

Interactions between C-reactive protein and traditional risk factors in predicting mortality of older adults.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are known to be associated with cardiovascular (CV) morbidity and mortality in older adults, however, there seems to be heterogeneity of this association across subsets of individuals. We aim to assess the effects of interactions between CRP and one of the following traditional CV risk factors regarding all-cause mortality in unselected elderly men and women: age, sex, body mass index, diabetes, and hypertension. PATIENTS AND METHODS: Three hundred and forty-four general practitioners all over Germany enrolled 6,817 unselected participants, aged 65 years or older, and performed thorough examinations, including CRP measurement at baseline (getABI study). All-cause mortality was determined in the following seven years. Cox regression analyses were done using uni- and multivariable models. RESULTS: At baseline 4,172 participants of this cohort had a CRP value of ≤ 3 mg/L (low level CRP group), 2,645 participants had a CRP value of > 3 mg/L (high level CRP group). The unadjusted hazard ratio for all-cause death of the high level CRP group compared to the low level CRP group was 1.49 (95 % confidence interval [95 %CI] 1.34 to 1.66). After adjustment for sex, age, education, peripheral artery disease/media sclerosis, other prior vascular events, smoking status, diabetes, systolic blood pressure, antihypertensive medication, body mass index, cholesterol, and statin use, the hazard ratio was 1.34 (95 %CI 1.20 to 1.50). Significant interactions with CRP were found for sex (adjusted hazard ratio 1.38, 95 %CI 1.11 to 1.72), age (0.75, 95 %CI 0.60 to 0.94), and baseline systolic blood pressure (0.64, 95 % CI 0.51 to 0.81). The interactions of CRP with body mass index and of CRP with diabetes were not significant. CONCLUSIONS: In older German adults, there seem to be effect modifications by age, sex, and arterial hypertension regarding the effect of CRP in the prediction of all-cause mortality.

Chronic but not inflammatory changes at the Achilles' tendon differentiate patients with peripheral spondyloarthritis from other diagnoses - Results from a prospective clinical trial.

BACKGROUND: Imaging has an essential role in the new spondyloarthritis (SpA) classification criteria for axial but not for peripheral manifestations. We evaluated the impact of imaging findings for identification and treatment decisions in patients with peripheral spondyloarthritis (pSpA) and controls (non-SpA). METHODS: Patients with pSpA (Assessment of SpA international Society criteria, n=30) and non-SpA (n=30), aged <45 years, with painful heels or knees, were recruited. Conventional radiography, grey-scale ultrasound including power Doppler (US/PDUS) and MRI of symptomatic areas were performed to assess inflammatory and structural changes. Mann-Whitney U test was used for group comparisons. RESULTS: In total, 105 painful entheses (71 heels, 34 knees) in 60 patients were examined. Differences between diagnoses were found for symptom duration (pSpA: 17.2±27.5 vs non-SpA: 4.4±4.3 months), human leucocyte antigen B27 prevalence (67% vs 13%) and gender distribution (53.3% vs 20% male, respectively), all P<0.05. Logistic regression analysis for baseline differences showed that chronic changes (erosions and calcification) in the heel were more frequent in pSpA versus non-SpA by US/PDUS (62.5% vs 28.6% patients and 59.5% vs 26.5% entheses, P<0.05). Inflammatory changes in heel or knee by US/PDUS and MRI could not differentiate between non-SpA and pSpA. CONCLUSIONS: Differentiation between pSpA and non-SpA was only possible based on structural but not inflammatory changes in the heels and knees of symptomatic patients. US/PDUS was superior to MRI for this purpose. These findings imply that pSpA is associated with erosive changes at enthesitic sites, while inflammation and susceptibility are of minor influence for the development of erosions and calcification to pSpA.

Response to methotrexate predicts long-term mortality of patients with rheumatoid arthritis independent of the degree of response: results of a re-evaluation 30 years after baseline.

OBJECTIVES: To assess if there is a correlation between the degree of response to treatment with methotrexate (MTX) and long-term mortality in a cohort of patients with rheumatoid arthritis (RA) established in Germany in the early eighties. METHODS: RA patients who had started MTX treatment between 1980 and 1987 were included. One year after baseline, the treatment response was evaluated. Responders were defined as patients with at least 20% decline in the swollen joint count (out of 32 joints) and the ESR with a prednisone dosage <5 mg/day. Thereafter, assessments were performed at 10, 18, and 30 years after baseline. Standardised mortality ratios (SMR) were calculated, Cox regression and logistic regression were performed. RESULTS: The cohort comprised 271 patients. In 2015, about 30 years after the initiation of MTX therapy, 185 patients (68%) were deceased, 52 (19%) lost to follow-up and 34 alive. The response after the first year of MTX treatment was the strongest predictor of survival with a hazard ratio of 0.44 (95% confidence interval [CI]: 0.30-0.65). However, even responders still had an SMR of 1.37 (95% CI 1.31-1.65), but this was much worse for non-responders who had an SMR of 4.22 (95% CI 3.13-5.56). Using Cox regression analysis no difference was detected between responders with more than 50% improvement (38% of all patients) and those with 20-50% improvement (28%). CONCLUSIONS: The predictive value of a response to one year of MTX therapy for long-term mortality of RA patients is independent of the degree of response.