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ObjectiveTo describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some.MethodsNationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge.ResultsOf 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group.ConclusionsIn this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.

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Aims In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. Methods and results This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011–2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1–2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden’s index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time Conclusion Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97–0.98), men vs. women: 1.88 (1.60–2.22), current vs. non-smoking: 0.76 (0.63–0.91), HLA-B27 positive vs. negative: 1.51 (1.20–1.91), TNF start year 2015–2018 vs. 2009–2014: 1.24 (1.06–1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectively Conclusion: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.

INTRODUCTION: Despite advances in treatment of patients with cardiogenic shock following acute myocardial infarction (AMICS) in-hospital mortality remains around 50%. Outcome varies among patient subsets and the elderly often have a poor a priori prognosis. We sought to investigate outcome among elderly AMICS patients referred to evaluation and treatment at a tertiary university hospital. METHODS: Current analysis was based on the RETROSHOCK registry comprising consecutive AMICS patients admitted to tertiary care. Patients in the registry were individually identified and validated. RESULTS: Of 1,716 admitted patients, 496 (28.9%) patients were ≥75 years old. Older patients were less likely to be admitted directly to a tertiary centre (59.4% vs. 69.9%, P = 0.003), receive mechanical support devices (i.e., Impella® (8.9% vs. 15.0%, P = 0.003), and undergo revascularization attempt (76.8% vs. 90.2%, P

Objectives. Implantable cardioverter defibrillator (ICD) implantation in patients resuscitated from out-of-hospital cardiac arrest (OHCA) due to acute myocardial infarction (AMI) is controversial. Design. Consecutive OHCA-survivors due to AMI from two Danish tertiary heart centers from 2007 to 2011 were included. Predictors of ICD-implantation, ICD-therapy and long-term survival (5 years) were investigated. Patients with and without ICD-implantation during the index hospital admission were included (later described as early ICD-implantation). Patients with an ICD after hospital discharge were censored from further analyses at time of implantation. Results. We identified 1,457 consecutive OHCA-patients, and 292 (20%) of the cohort met the inclusion criteria. An ICD was implanted during hospital admission in 78 patients (27%). STEMI and successful revascularization were inversely and independently associated with ICD-implantation (ORSTEMI = 0.37, 95% CI: 0.14–0.94, ORrevasc = 0.11, 0.03–0.36) whereas age, sex, LVEF logrank = 0.02), which was persistent after adjustment for prognostic factors (HR = 0.44 (95% CI: 0.23–0.88)). This association was no longer found when using first event (death or appropriate shock whatever came first) as outcome variable (plogrank = 0.9). Conclusions. Mortality after OHCA due to AMI was significantly lower in patients with early ICD-implantation after adjustment for prognostic factors. When using appropriate shock and death as events, ICD-patients had similar outcome as patients without an ICD, which may suggest a survival benefit due to appropriate device therapy.

Aims The aims of this study were to investigate the correlation and sex differences between total valve calcium, valve calcium concentration, and aortic valve calcification (AVC) in explanted valves from patients with severe aortic valve stenosis undergoing aortic valve replacement (AVR). Methods and results Sixty-nine patients with severe aortic stenosis (AS) scheduled for elective AVR underwent echocardiography and cardiac computed tomography (CT) prior to surgery (AVCin vivo) and CT of the explanted aortic valve (AVCex vivo). Explanted valves were prepared in acid solution, sonicated, and analysed with Arsenazo III dye to estimate total valve calcium and valve calcium concentration. Median AVCex vivo was 2082 (1421–2973) AU; mean valve calcium concentration was 1.43 ± 0.42 µmol Ca2+/mg tissue; median total valve calcium 156 (111–255) mg Ca2+, and valve calcium density 52 (35–81) mg/cm2. AVC displayed a strong correlation with total valve calcium (R2 = 0.98, P Conclusion AVC score provides a strong estimate for total valve calcium but to a lesser degree calcium concentration in the valve tissue of patients with severe AS. Females presented lower valvular calcium concentrations than males irrespective of AS severity, adding evidence and providing support to the important point that sex differences in valvular calcium concentration in AS does not reflect valvular size.

Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody–associated vasculitis that affects mainly small-sized vessels and is characterized by upper and lower respiratory tract, kidney, eye, skin, and neurologic involvement.

Introduction: In refractory out-of-hospital cardiac arrest (OHCA), prolonged whole-body ischemia with global tissue injury proceeds even after achievement of reperfusion with extracorporeal cardiopulmonary resuscitation (eCPR). Hypothesis: Biomarkers reflecting ischemia and inflammation may be used for prognostication of refractory OHCA managed with eCPR. Methods: This nationwide retrospective study included patients (≥18 years) with refractory OHCA managed with eCPR in Denmark (2011 to 2020). Biomarker levels at admission, at 24 hours (lactate, leukocytes, and platelets), and repeated measures of lactate after eCPR initiation were analyzed. Lactate clearance was calculated as (admission lactate - post eCPR lactate) / admission lactate x100%. Results: Two hundred eighteen patients (80% male; age 52±12yrs) were included. Primary cause of OHCA was acute myocardial infarction (63%), 69% had shockable primary rhythm and 86% witnessed OHCA with a median low-flow time of 105 minutes (Q1-Q3: 86-124 min.). Fifty-three (24%) survived to hospital discharge. Survivors had a significantly lower lactate level at admission (13.1 vs. 15.4 mmol/l, p=0.004) and after 24 hours (2.8 vs. 5.0, p=0.001), and a significantly higher admission platelet level (181 vs. 153 x10 9 /l, p=0.03). No difference in admission levels of leukocytes nor leukocytes and platelets after 24 hours were found between survivors and non-survivors. Lactate clearance was available for 68% and 79% of patients alive after 8 and 24 hours, respectively. All survivors had a lactate level less than admission lactate at 8 hours (lactate clearance >0%) and had cleared >25% of admission lactate at 24 hours after eCPR initiation. There was a significant difference in survival between quartiles of lactate clearance at 8 hours after eCPR initiation (Figure 1). Conclusion: In conclusion, early lactate clearance after eCPR initiation was associated with survival to discharge in refractory OHCA-patients.

Background Extracorporeal cardiopulmonary resuscitation (ECPR) has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). Despite growing interest in and a growing body of literature on ECPR for refractory OHCA, robust evidence on patient eligibility is still lacking. Purpose To describe the survival, neurological outcome, and adherence to the national consensus with respect to use of ECPR for OHCA, and to identify factors associated with outcome. Methods Retrospective, observational cohort study of patients who underwent ECPR for OHCA at four cardiac arrest centres. Binary logistic regression and Kaplan-Meier survival curves were performed to assess association with 30-day mortality. Results A total of 259 patients receiving ECPR for OHCA between July 2011 and December 2020 were included in the study. Thirty-day survival was 26% and a good neurological outcome Cerebral Performance Category (CPC) 1–2 was observed in 94% of patients at discharge. Strict adherence to the national consensus showed a 30-day survival rate of 30%. Adding one or more of the following criteria to the national consensus: signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow 6.8 and lactate 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had threefold higher survival rate than patients without signs of life (45% versus 13%, p Conclusion A high survival rate with a good neurological outcome was observed in this population of patients treated with ECPR for OHCA. Signs of life during CPR may aid the decision-making in the selection of appropriate candidates. Stringent patient selection for ECPR may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors, why optimization of the selection criteria is still necessary. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported by the Danish Heart Foundation [20-R142-A9498-22178]; and Health Research Foundation of Central Denmark Region [R64-A3178-B1349] Survival and adherence to consensusSigns of life during CPR

Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.

This review provides a summary of treatment of cardiac arrest with mechanical cardiopulmonary resuscitation (CPR). CPR provides chest compressions according to guidelines in the treatment of out-of-hospital cardiac arrest. This is useful in situations where CPR cannot be safely delivered (e.g. during transportation and prolonged CPR). Randomized controlled trials have not shown improved patient outcomes after treatment with mechanical CPR compared to manual CPR. Mechanical CPR can, like manual CPR, cause injuries, and some may be life-threatening. Mechanical CPR is therefore recommended as an adjunct to manual CPR in special circumstances but not used routinely.

AIMS: The aim of this study was to evaluate the Impella CP over veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and their impact on left ventricular unloading and end-organ perfusion.METHODS AND RESULTS: Cardiogenic shock (CS) was induced by injecting microspheres into the left coronary artery in fourteen adult female swine. Impella CP or VA-ECMO was initiated in the presence of CS and evaluated after 60 minutes. Left ventricular pressure-volume area (PVA, total mechanical work) was obtained from a conductance catheter. Results are presented as mean (95% confidence interval) and the rank-sum test was used to assess differences between devices. Compared to the CS state, PVA was unaffected by Impella CP and increased on VA-ECMO (from 2,548 [2,193; 2,904] mmHg x mL during CS to 5,775 [4,451; 7,099], between device p-value=0.02). Arterial lactate increased during CS and decreased on support with no difference between devices. Renal venous oxygen saturation decreased during CS and increased on support with no difference between devices. Cerebral venous oxygen saturation increased to 33% [25, 40] on Impella CP and to 69% [49, 89] on VA-ECMO, p=0.04.CONCLUSIONS: In this porcine model of profound CS, Impella CP unloaded the left ventricle compared to VA-ECMO. Both devices improved end-organ perfusion, with a tendency towards higher venous oxygen saturations on VA-ECMO.

Background Patients with RA have shorter life expectancy than the background population. Severe disease, as reflected in high disease activity, comorbid conditions and functional disability have historically been associated with increased mortality (1-2). Mortality after the introduction of biological therapies has not been investigated in detail, and little is known about the predictive value of sociodemographic and lifestyle factors. Objectives To investigate the predictive value of a panel of potential predictors of death in a cohort of patients with RA followed for up to 12 years during the era of biological treatments. Methods Outpatients with RA were recruited consecutively between July 2006 and July 2007 and followed in routine care with prospective registrations in the DANBIO registry until death or August 30th 2018, whichever occurred first. Baseline variables considered to be potential predictors were: disease activity, disease duration, IgM-rheumatoid factor (IgM-RF), radiographic status (erosive disease yes/no) and medical therapy as well as patient-reported marital status, educational level, comorbid conditions, smoking, exercise, body mass index (BMI) and health assessment questionnaire (HAQ). Vital status and date of death were extracted from the Danish National Register. A cox proportional hazards model was used to estimate the hazard ratio for death for each of the potential predictors. Results 3693 patients were recruited at baseline, 75% women, 77% IgM-rheumatoid factor positive, 65% with erosive disease, median (IQR) age 62 years (52-71), disease duration 7 years (3-15), DAS28 3.0 (2.2-3.9), HAQ 0.63 (0.25-1.25). 20% received a biological disease modifying anti-rheumatic drug (DMARD), 71% received a synthetic DMARD and 9% received no DMARD. The median (IQR) duration of follow-up was 11 years (9-11); 1041 patients (28%) died during follow-up. 640 patients were excluded from the regression model due to missing baseline data; these individuals were slightly (median of 3 years) older than those who entered, but with similar disease duration and disease activity. All baseline variables were statistically significant predictors in univariable analyses. Table shows hazard ratio estimates in the multivariable model, which included 3053 patients; 762 (25%) deaths. IgM-RF positivity, higher HAQ score, glucocorticoid therapy, smoking (current and former) and two or more comorbid conditions were predictors of death. Low BMI was a borderline significant predictor for death. Female sex, weekly exercise and cohabiting decreased the risk of death. Conclusion In a large cohort of RA patients followed for a decade in the era of biological treatments, we identified strong clinical (high HAQ, comorbidity), treatment related (glucocorticoid last month), sociodemographic and lifestyle related (male sex, living alone, smoking, physical inactivity, low BMI) risk factors for death. In the effort to prevent a poor long term outcome in patients with RA, this study provides new insight into potentially modifiable baseline variables. References [1] Mok, CC, et al. Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China. Arthritis Rheum2011; 63: 1182-1189. [2] Sokka, T, et al. Mortality in rheumatoid arthritis: 2008 update. Clin exp Rheumatol. 2008Sep-Oct; 26 (5 suppl 51) S: 35-61. Acknowledgement We thank the Danish Rheumatism Association for supporting the study. Disclosure of Interests Louise Linde: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis

Objectives. To investigate travel time, and travel cost related to contacts with health care providers for patients with rheumatoid arthritis (RA) during a three-month period.Methods. Patient-reported travel time and travel cost were obtained from 2847 patients with RA. Eleven outpatient clinics across Denmark recruited patients to the study. Data collected included frequency, travel time and travel costs for contacts at rheumatology outpatient clinics, other outpatient clinics, general practitioners, privately practicing medical specialists, inpatient hospitals and accident and emergency departments.Results. Over a 3-month period, patients with RA had on average 4.4 (sd 5.7) contacts with health care providers, of which 2.8 (sd 4.0) contacts were with rheumatology outpatient clinics. Private car and public travel were the most frequent modes of travel. The average patient spent 63 minutes and 13 € on travelling per contact, corresponding to a total of 4.6 hours and 56 € during the 3-month period. There was great variation in patient travel time and costs, but no statistically significant associations were found with clinical and sociodemographic characteristics.Conclusion. The results show that patients with RA spend private time and costs on travelling when they seek treatment. These findings are particularly important when analyzing social costs associated with RA.

Objectives To investigate the incidence of cancer in arthritis patients treated with or without TNFα inhibitors (TNF-I). Methods Arthritis patients from the DANBIO database were followed-up for cancer in the Danish Cancer Registry during 2000–2008. Results Hazard ratio for cancer overall was 1.02 (95% confidence interval (CI) 0.80-1.30) in 3347 TNF-I-treated RA patients compared to non-treated. Excess among TNF-I-treated was found for colon cancer (HR 3.52 (95%CI 1.11-11.15), whereas 6 and 0 ovarian cancer cases were observed in treated and non-treated patients, respectively. Compared to the general population, TNF-I-treated RA patients had increased risk for cancer overall, cancer in lymphatic-haematopoietic tissue and non-melanoma skin cancer, while non-RA patients had no increase in overall cancer risk. Conclusions Our results suggest that TNF-I therapy in routine care is not associated with an overall excess of cancer in arthritis patients, but observed increased risks of colon and ovarian cancer need further investigation.

Background The aim of this study was to compare quality-adjusted life expectancy (QALE) for patients with rheumatoid arthritis generated from three generic health-related quality-of-life instruments. Methods Patients from 11 Danish rheumatology outpatient clinics were asked to report current health status using the EuroQol five-dimensional questionnaire (EQ-5D), 15D, and six-dimensional health state short form (derived from SF-12) (SF-6D) instruments. Clinical staff provided data on current disease status (C-reactive protein and Disease Activity Score that involves clinical assessment of 28 joints). National mortality data were retrieved from Statistics Denmark. For each of the three instruments, mean index scores were estimated by gender and 5-year age groups. Partial QALE was estimated for the age interval 30 to 79 years for different subsamples. Results Although the three quality-of-life index scores were highly correlated, there were statistically significant differences between the average index scores from the three instruments. The 15D provided the highest index score and SF-6D the lowest score. For a 30-year-old patient, the partial QALE ranged from 37.9 quality-adjusted life-years using the SF-6D to 45.6 quality-adjusted life-years using the 15D. The QALE for men and women differed by 6.2%, 4.0%, and 5.3% when the calculation was based on EQ-5D, SF-6D, and 15D index scores, respectively. The largest differences were observed when patients were grouped by functional status (Health Assessment Questionnaire score), where the EQ-5D showed a 50% difference in index score between the best and worst functional group while the SF-6D and 15D showed smaller differences (32% and 14%, respectively). Discussion This analysis has shown the difference in QALE estimates related to different instruments. The study emphasizes that unless outcome studies use the same instruments and scoring algorithms, the results will not be directly comparable.

Aortic valve calcification score (AVC) estimated by cardiac Computed Tomography (CT) can be used in the evaluation of aortic valve stenosis (AS) but few studies have investigated the correlation with total calcium weight in the valve tissue. 69 patients with AS scheduled for aortic valve

Objective. To compare health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA) to that of the general population and to investigate the association with disease activity, focusing on different clinical remission criteria.Methods. EQ-5D data from 3156 patients with RA from 11 Danish centers were compared with Danish EQ-5D population norms (n = 16,136). The Disease Activity Score (DAS28) and the Clinical Disease Activity Index score (CDAI) were used as definitions of disease activity and clinical remission. The score difference (ΔEQ-5D) was calculated in each patient as the difference from the age and sex-matched general population and adjusted for age, marital status, education, body mass index, smoking, exercise habits, disease duration, IgM-rheumatoid factor status, joint surgery, extraarticular features, treatment, and comorbidity in multiple linear regression models.Results. 37% vs 22% fulfilled the DAS28 and CDAI remission criteria, respectively. The ΔEQ-5D values for women/men in clinical remission were DAS28 0.05/0.06 vs CDAI 0.01/0.02; low disease activity: DAS28 0.12/0.13 vs CDAI 0.11/0.14; moderate disease activity: DAS28 0.18/0.20 vs CDAI 0.20/0.23; and high disease activity: DAS28 0.38/0.28 vs CDAI 0.33/0.26. Adjusting for confounders reduced the ΔEQ-5D values between 0 and 0.04 units.Conclusion. Patients with RA had worse EQ-5D scores than the general population, and the difference was strongly associated with disease activity. The EQ-5D score for patients in clinical remission approached that of the general population, suggesting that strict treatment goals are critical in order to achieve near-normal HRQOL in patients with RA.

Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously reported functional effects were associated with clinical response to TCZ in a retrospective study cohort consisting of 79 RA patients. Three months after initiation of TCZ therapy, changes in swollen joint count (SJC) and, subordinately, tender joint count (TJC), serum-CRP, DAS28-CRP, and EULAR-response were tested for association with the IL6R-haplotype or genotype. The major allele (A) of rs12083537 and the minor allele (C) of rs4329505 were associated with a poor SJC response (P=0.02 and 0.02, respectively). Moreover, the AAC-haplotype (for rs12083537, rs2228145, and rs4329505, respectively) was associated with a poor SJC response (P=0.00004) and, with borderline significance, EULAR-response (P=0.05). These data suggest that genetic variation in IL6R may aid in predicting TCZ therapy outcome in RA patients.

Objective.The quality-adjusted life-year (QALY) is used to measure outcome in rheumatoid arthritis (RA) studies; identification of drivers of a gain in QALY might help predict a treatment response. We investigated how changes in components of the Disease Activity Score-28 joints (DAS28) were associated with the European League Against Rheumatism (EULAR) and European Quality of Life 5 Dimensions (EQ-5D) responses; and what baseline variables predicted the change in QALY following 1 year of biological therapy.Methods.Data were collected at baseline and after 3, 6, and 12 months of biological therapy in Danish patients with RA and included bDAS28, sociodemographic data, comorbidity, Health Assessment Questionnaire (HAQ), and EQ-5D scored using the Danish algorithm. A cross-tabulation based on EULAR versus EQ-5D responses was performed, and the association of each DAS28 component across the EULAR/EQ-5D response groups was tested. Predictors of a change in QALY were assessed in a multiple regression model including baseline clinical and patient-reported data as explanatory variables.Results.In total, 315 patients entered the study; 77% were women, 78% IgM rheumatoid factor-positive, with mean age 55 (SD 13) years, disease duration 10 (SD 8) years, mean DAS28 4.9 (SD 1.2), HAQ score 1.22 (SD 0.70), and EQ-5D score 0.60 (SD 0.19). Sixty-eight percent of patients gained QALY; the mean gain was 0.14 (SD 0.13). The patient global score was strongly correlated with both EULAR and EQ-5D responses. The gain in QALY increased with increasing patient global score and number of swollen joints, but not with C-reactive protein (CRP).Conclusion.The subjective patient global score was the best baseline predictor of gain in QALY following biological therapy, while the objective CRP measure had no predictive value. It seems that no sharp demarcation between objective and subjective measures could be determined.

Lost production can be due to individuals’ time lost to work (absenteeism), as well as their time at work with reduced productivity because of ill health (presenteeism). A sound methodological framework for the assessment of presenteeism remains to be established but given its significance, ignoring it would lead to severe underestimations, eg, in cost-of-illness studies. The objective of this study was to assess the empirical significance of absenteeism and presenteeism in terms of production loss using the case of rheumatoid arthritis (RA). Selected modules from the Health and Labor Questionnaire were applied in a cross-sectional study of 3,704 patients with RA. The costs of absenteeism and presenteeism were estimated using the Human Capital approach, and the impact of including multipliers adjusting for the productivity effect of a workers’ absence or impaired presenteeism on societal productivity was demonstrated. RA-related absenteeism over the last 14 days was 22.31 hours (standard deviation [SD], 26.51) with a resulting cost of €473 (SD, 575) and €762 (SD, 926) depending on whether a multiplier was included. Presenteeism was found to affect 7.98 (SD, 3.24) working days over the last 14 days with a resulting cost of €168 (SD, 203) and €203 (SD, 245), again depending on whether a multiplier was included. Overall, this article demonstrates that the value of lost production due to RA could be subject to an almost factor 2 increase if productivity effects of presenteeism and general multipliers are included.

Udgivelsesdato: 2010-Jan OBJECTIVE: To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. METHODS: The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). RESULTS: Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80). CONCLUSION: Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.

Objective.The Health Assessment Questionnaire Disability Index (HAQ) is a widely used outcome measure in rheumatoid arthritis (RA), whereas the SF-12v2 Health Survey (SF-12) was introduced recently. We investigated how the HAQ and SF-12 were associated with socio-demographic, lifestyle, and disease- and treatment-related factors in patients with RA.Methods.In RA patients from 11 Danish centers, clinical and patient-reported data, including the HAQ and SF-12, were collected. Three multiple linear regression models were estimated, with the HAQ, SF-12 physical component score (PCS), and SF-12 mental component score (MCS) as outcome and sociodemographic, lifestyle, and RA-related treatment and comorbidity characteristics as explanatory variables.Results.In total, 3156 (85%) of 3704 invited patients participated — 75% women, 76% rheumatoid factor-positive, median age 61 years (range 15–93 yrs), disease duration 7 years (range 0–68 yrs), Disease Activity Score on 28 joints (DAS28) 2.97 (range 0.96–8.61), HAQ score 0.63 (range 0–3), SF-12 PCS 56 (range 6–99), and SF-12 MCS 57 (range 16–99). Variation in HAQ was associated with 12 of 15 possible variables (R2 0.41), in PCS and MCS with 6 of 15 variables (R2 0.02 and 0.05). Patients with moderate to high DAS28 and ≥ 3 comorbid conditions had consistently worse HAQ and SF-12 scores compared to the reference groups, while weekly exercise was associated with better scores compared to no exercise.Conclusion.The HAQ was more sensitive to differences in demographic, lifestyle, and disease- and treatment-related factors than the SF-12. The established clinical value and feasibility of the HAQ highlights its advantages over the SF-12 in describing health status in RA.

To compare validity, reliability, and responsiveness of generic and disease specific health-related quality of life (HRQOL) instruments in rheumatoid arthritis (RA).Two samples of patients completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36), EuroQol (EQ)-5D, 15D, Rheumatoid Arthritis Quality of Life Scale (RAQoL), Health Assessment Questionnaire (HAQ), and visual analog scales (VAS) for pain, fatigue, and global RA. VALIDITY (convergent, discriminant, and known-groups) was evaluated in a cross-section of 200 patients. Reliability was evaluated by agreement (intraclass correlation coefficient; baseline to 2 weeks) and internal consistency (Cronbach's alpha); and responsiveness by the standardized response mean stratified on improvement, status quo, or deterioration in health status after 6 months in 150 patients followed longitudinally. Followup questionnaires (at 2 weeks and 6 months) included questions about changes in health status since baseline.The cross-sectional sample included 77% women, median age 57 years (range 19-87), disease duration 6 years (0-58), with Disease Activity Score 28-joint count (DAS28) of 3.10 (1.21-6.47). The longitudinal sample included 80% women, median age 60 years (22-82).all instruments discriminated between low, moderate, and high DAS28. Reliability: RAQoL and HAQ displayed good repeatability (ICC0.95) and internal consistency (Cronbach's alpha0.90). Responsiveness: SF-36 bodily pain scale and VAS pain were responsive to both improvement and deterioration.All instruments were valid measures for HRQOL in RA. The RAQoL and HAQ displayed the best reliability, while the SF-36 bodily pain scale and VAS pain were the most responsive. The choice of instrument should depend on the study objectives.

Rheumatoid arthritis (RA) is a chronic inflammatory disease causing joint pain, loss of function and decreased health-related quality of life (HRQoL). HRQoL in RA patients is associated with several risk factors; in this paper the evidence relating to the most important risk factors is reviewed. Modern medical therapy has improved HRQoL in RA patients, while demographic factors (female sex and older age), low socioeconomic status (in terms of education and position in the work force) and the presence of comorbid conditions appear to be associated with poorer HRQoL.

To assess the drug survival and reasons for discontinuation of intramuscular methotrexate (imMTX) in rheumatological patients who had switched to imMTX from oral methotrexate (oMTX).Data from 212 consecutive patients who switched from oMTX to imMTX therapy at our outpatient clinic between April 1997 and January 2004 were collected retrospectively through survey of case records. Data included reason for discontinuation of oMTX, disease activity parameters, duration of imMTX therapy, and, in patients who withdrew, the reason for discontinuation of imMTX.The main reasons for switching from oMTX to imMTX were lack of efficacy (66%) and adverse events (28%). After 6 months, 114 patients (54%) were still receiving imMTX therapy, and their median serum C-reactive protein (CRP) and the percentage of patients who had received glucocorticoids during the previous 6 weeks had decreased (p0.001). The median survival of imMTX therapy was 7.5 months (interquartile range 3-17). Twenty per cent of the patients received imMTX for more than 24 months. Of the 212 patients, 41% and 9% stopped imMTX therapy because of lack of efficacy and adverse events, respectively. Of the patients who had stopped oMTX because of adverse events, 22% also withdrew from imMTX because of adverse events.Half of the patients benefited from switching from oral to intramuscular methotrexate for at least 6 months, but only a minority adhered to the treatment for years. Lack of efficacy was the most frequent reason for discontinuation, while adverse events were rare.

Background The Quality Adjusted Life Year (QALY), based on health-related quality of life measures such as euroqol 5 dimensions (EQ-5D), is an important outcome in rheumatoid arthritis (RA) studies, as it facilitates comparative analyses of cost-effectiveness. Identifying drivers of a gain in QALY would be helpful in predicting who may respond to a given treatment. Objectives To investigate how each of the four DAS28 components are associated with the EULAR and EQ-5D responses, and what baseline variables that are predictive of the gain in QALY following one year of biological therapy. Methods Clinical and patient-reported data were collected at baseline, three months, six months and one year in outpatients with RA initiating biological therapy in routine care. A cross-tabulation based on EULAR versus EQ-5D responses was performed, and the association of each of the four DAS28 components across the EULAR/EQ-5D response groups was tested. For EQ-5D, an improvement above the minimally important difference (MID) of 0.05 units (1) was considered a response. A moderate or good EULAR treatment response at one year was considered a EULAR response. Patients who withdrew from treatment were considered EULAR non-responders. Predictors of a gain in QALY were assessed in a multiple regression model including baseline clinical and patient-reported data as explanatory variables. Results A total of 315 patients entered the study, 33 were lost to follow-up. Baseline characteristics: 77% women, 78% IgM rheumatoid factor positive, mean (SD) age: 55 (13) years, disease duration: 10 (9) years, DAS28: 5.0 (1.2), HAQ-score: 1.24 (0.70), EQ-5D: 0.59 (0.19). Among each of the four DAS28 components, the patient global RA assessment on a visual analogue scale (VAS) was most strongly associated with both EULAR and EQ-5D responses. Thus, 5 of the 6 possible group comparisons were highly significant (p Eighty % of the patients gained QALY after one year of biological therapy; their mean (SD) gain was 0.14 (0.13). The gain in QALY increased by 0.016 per cm of increase in baseline patient global RA assessment and 0.004 per baseline swollen joint increase, and patients with two or more extra-articular manifestations gained 0.106 more QALY’s compared with those without such manifestations. Conclusions Among the four DAS28 components, the patient global RA assessment was most strongly associated with both EULAR and EQ-5D responses, and it was also a baseline predictor of the gain in QALY achieved after one year of therapy. As the four DAS28 components showed different characteristics, the components may need to be analyzed separately when used in cost-effectiveness studies. References Marra et al. A comparison of generic, indirect utility measures (the HUI2, HUI3, SF-6D, and the EQ-5D) and disease-specific instruments (the RAQoL and the HAQ) in rheumatoid arthritis. Soc Sci Med 2005 Apr;60(7):1571-82. Disclosure of Interest None Declared

Rikke Søgaard1, Jan Sørensen1, Louise Linde2, Merete L Hetland2,31CAST – Centre for Applied Health Services Research and Technology Assessment, University of Southern Denmark, Denmark; 2Department of Rheumatology, Hvidovre and Glostrup Hospitals, Denmark; 3The DANBIO registry, Hvidovre and Glostrup Hospitals, DenmarkAbstract: Lost production can be due to individuals’ time lost to work (absenteeism), as well as their time at work with reduced productivity because of ill health (presenteeism). A sound methodological framework for the assessment of presenteeism remains to be established but given its significance, ignoring it would lead to severe underestimations, eg, in cost-of-illness studies. The objective of this study was to assess the empirical significance of absenteeism and presenteeism in terms of production loss using the case of rheumatoid arthritis (RA). Selected modules from the Health and Labor Questionnaire were applied in a cross-sectional study of 3,704 patients with RA. The costs of absenteeism and presenteeism were estimated using the Human Capital approach, and the impact of including multipliers adjusting for the productivity effect of a workers’ absence or impaired presenteeism on societal productivity was demonstrated. RA-related absenteeism over the last 14 days was 22.31 hours (standard deviation [SD], 26.51) with a resulting cost of €473 (SD, 575) and €762 (SD, 926) depending on whether a multiplier was included. Presenteeism was found to affect 7.98 (SD, 3.24) working days over the last 14 days with a resulting cost of €168 (SD, 203) and €203 (SD, 245), again depending on whether a multiplier was included. Overall, this article demonstrates that the value of lost production due to RA could be subject to an almost factor 2 increase if productivity effects of presenteeism and general multipliers are included.Keywords: work limitations, Health and Labor Questionnaire, productivity, production loss