Rheumatoid arthritis and risk of osteoarticular infection and death following Staphylococcus aureus bacteraemia: A nationwide cohort study.

OBJECTIVES: Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA. METHODS: Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006-2018. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants, antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression). RESULTS: We identified 18 274 patients with SAB (n = 367 with RA). The 90-day cumulative incidence of OAI was 23.1%(95%CI 18.8; 27.6) for patients with RA and 12.5%(12.1; 13.0) for patients without RA (non-RA) (HR 1.93(1.54; 2.41)). For RA patients with orthopaedic implants cumulative incidence was 29.4%(22.9; 36.2) (HR 1.75(1.08; 2.85), and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9%(27.0; 56.1) (HR 2.27(1.29; 3.98) compared with non-users). All-cause 90-day mortality following SAB was similar in RA (35.4%(30.6; 40.3)) and non-RA (33.9%(33.2; 34.5), HR 1.04(0.87; 1.24)). CONCLUSION: Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI.

Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: a nationwide nested case-control study.

OBJECTIVES: To assess how biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids and disease activity affect risk of Staphylococcus aureus bacteraemia (SAB) in patients with rheumatoid arthritis (RA). METHODS: In a nationwide cohort of patients with RA from the DANBIO registry, we conducted a nested case-control study including first-time microbiologically verified SAB cases from 2010 to 2018 and incidence density matched controls (1:4 by sex, age). We interlinked Danish registries and identified antirheumatic treatments, RA-specific clinical characteristics, comorbidities and socioeconomic status. The relative risk of SAB was assessed by adjusted ORs with 95% CIs and number needed to harm (NNH) reflected the absolute risk. RESULTS: Among 30 479 patients, we identified 180 SAB cases (incidence rate: 106.7/100 000 person-years) and matched 720 controls (57% women, median age 73 years, IQR: 65-80). Risk of SAB was increased in current (OR 1.8 (95% CI 1.1 to 3.2)) and former bDMARD users (OR 2.5 (95% CI 0.9 to 7.0)), and in current users of oral glucocorticoids ≤7.5 prednisolone-equivalent mg/day (OR 2.2 (95% CI 1.3 to 4.0) and >7.5 mg/day (OR 9.5 (95% CI 3.9 to 22.7)) (non-use as reference). ORs for moderate/high disease activity compared with remission were 1.6 (95% CI 0.8 to 3.3)/1.5 (95% CI 0.6 to 4.3). Risk was increased in patients with longstanding RA (>10 years vs ≤3 years, OR=2.4 (95% CI 1.1 to 5.3)). The NNH was 1172(95% CI 426 to 9374) for current use of bDMARDs and 110(95% CI 43 to 323) for glucocorticoids >7.5 mg/day. CONCLUSION: We identified a dose-dependent increased risk of SAB in patients with RA currently using oral glucocorticoids. Daily use of >7.5 mg appeared to be a clinically relevant risk factor, whereas the absolute risk was low for bDMARDs. No clear impact of disease activity was found.

Infliximab biosimilar-to-biosimilar switching in patients with inflammatory rheumatic disease: clinical outcomes in real-world patients from the DANBIO registry.

OBJECTIVE: Successful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). METHODS: Observational cohort study from the DANBIO registry. Patients were classified as originator-naïve or originator-experienced. Retention rates of 1-year GP1111 treatment were explored (Kaplan-Meier). We identified baseline factors (at the time of switch) associated with withdrawal of GP1111 (multivariable Cox-regression analyses with HRs including originator treatment history). Changes in subjective and objective measures of disease activity 4 months before and after the switch were assessed in individual patients. RESULTS: Of 1605 patients (685 RA, 314 PsA and 606 AxSpA, median disease duration was 9 years, 37% in Clinical Disease Activity Index/Ankylosing Spondylitis Disease Activity Score remission), 1171 were originator-naïve. Retention rates at 1-year were 83% (95% CI: 81% to 85%) and 92% (95% CI: 90% to 95%) for the originator-naïve and originator-experienced, respectively. GP1111 retention rates were higher in originator-experienced compared to originator-naïve with RA (HR=0.4 (95% CI: 0.2 to 0.7)) and PsA (HR=0.2 (95% CI: 0.1 to 0.8)), but not significantly for AxSpA: HR=0.6 (95% CI: 0.3 to 1.2). Lower disease activity was associated with higher retention. Changes in disease activity preswitch and postswitch were close to zero. CONCLUSION: This real-world observational study of more than 1600 patients with inflammatory arthritis showed high 1-year retention following a nationwide infliximab biosimilar-to-biosimilar switch. Retention was higher in originator-experienced and in patients with low disease activity, suggesting outcomes to be affected by patient-related rather than drug-related factors.

Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial.

OBJECTIVES: In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA). METHODS: Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months' remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication). RESULTS: Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months' remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched. CONCLUSION: This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.

Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model.

OBJECTIVES: Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with that in the general population and, second, to develop a simple clinical prediction model and to obtain risk estimates for individual patients. METHODS: This was a matched-cohort study based on nationwide registries in Denmark. Patients with RA, axial SpA and PsA initiating first bDMARD monitored in the DANBIO registry were matched 1:10 by age, gender and postal code with controls from the general population. The risk of serious infection during 12 months' follow-up was assessed with Cox regression. Prediction models were developed using logistic regression and compared using area under the receiver operating characteristic curve (AUC). RESULTS: We included 11 372 patients and 113 715 controls. During follow-up, 522 patients (4.6%) and 1434 controls (1.3%) developed a serious infection (hazard ratio 3.7, 95% CI 3.4, 4.1). Age-stratified risk was largely similar across diagnoses. A simple prediction model, the 'DANBIO infection risk score', based on age and a count of six clinical risk factors had moderate discriminative power (internal validation: AUC 0.69) that was comparable to that of the existing RABBIT (Rheumatoide Arthritis Beobachtung der BIologika-Therapie) Risk Score (external validation: AUC 0.68). CONCLUSION: Patients with inflammatory joint diseases initiating bDMARD treatment had a four times increased risk of serious infection compared with the general population. A simple prediction model, feasible for shared decision-making, was developed to obtain risk estimates for individual patients.

Overall infection risk in rheumatoid arthritis during treatment with abatacept, rituximab and tocilizumab; an observational cohort study.

OBJECTIVES: Most infections in patients with RA are treated in primary care with antibiotics. A small fraction require hospitalization. Only a few studies exist regarding the overall risk of infection (i.e. prescription of antibiotics or hospitalization due to infection) in patients initiating non-TNF-inhibitor therapy. In Danish RA patients initiating abatacept, rituximab and tocilizumab treatment in routine care, the aims were to compare adjusted incidence rates (IR) of infections and to estimate relative risk of infections across the drugs during 0-12 and 0-24 months. METHODS: This was an observational cohort study including all RA patients in the DANBIO registry starting a non-TNF-inhibitor from 2010 to 2017. Infections were defined as a prescription of antibiotics or hospitalization due to infection. Prescriptions, comorbidities and infections were captured through linkage to national registries. IRs of infections (age, gender adjusted) and rate ratios (as estimates of RR (relative risk)), adjusted for additional covariates) (Poisson regression) were calculated. RESULTS: We identified 3696 treatment episodes (abatacept 1115, rituximab 1017, tocilizumab 1564). At baseline, rituximab users were older and had more previous cancer. During 0-12 months, 1747 infections occurred. Age and gender-adjusted IRs per 100 person-years were as follows: abatacept: 76 (95% CI: 69, 84); rituximab: 87 (95% CI: 79, 96); tocilizumab: 77 (95% CI: 71, 84). Adjusted RRs were 0.94 (95% CI: 0.81, 1.08) for abatacept and 0.94 (95% CI: 0.81, 1.03) for tocilizumab compared with rituximab and 1.00 (95% CI: 0.88, 1.14) for abatacept compared with tocilizumab. RRs around 1 were observed after 24 months. Switchers and ever smokers had higher risk compared with biologic-naïve and never smokers, respectively. CONCLUSION: Overall infections were common in non-TNF-inhibitor-treated RA patients, with a tendency towards rituximab having the highest risk, but CIs were wide in all analyses. Confounding by indication may at least partly explain any differences.

Risk factors for Staphylococcus aureus bacteremia in patients with rheumatoid arthritis and incidence compared with the general population: protocol for a Danish nationwide observational cohort study.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is an invasive infection with high mortality and morbidity. Rheumatoid arthritis (RA) is associated with increased risk of infections due to the disease per se and the use of antirheumatic treatments. Few minor studies have previously investigated risk of SAB in patients with RA and indicated increased risk compared with the general population. This nationwide observational study aims to investigate incidence of and risk factors for SAB in adult patients with RA compared with the general population. The effect of disease characteristics (eg, joint erosions, disease duration and activity), different antirheumatic treatments and smoking on SAB risk will be evaluated. METHODS AND ANALYSIS: All adults (>18 years of age) alive and living in Denmark in 1996-2017 will be identified in The Danish Civil Registration System. Incident patients with RA are identified in the Danish National Patient Registry (DNPR) and the nationwide rheumatology registry, DANBIO, in which information on, for example, antirheumatic treatments, disease characteristics and smoking is collected prospectively in routine care. Information on comorbidities, invasive procedures and prescribed drugs are identified in the DNPR and in The Register of Medicinal Product Statistics. Socioeconomic status is evaluated in national registers on income and education. Incident cases of first-time SAB are identified in The Danish National SAB Database. All registers are linked on an individual level by unique civil registration numbers. Incidence rates and incidence rate ratios will be analysed using Poisson regression models and the impact of possible risk factors will be evaluated. ETHICS AND DISSEMINATION: All data will be handled in accordance with the General Data Protection Regulation (EU) 2016/679. No ethical approval is necessary in Denmark when handling registry data only. The results will be presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology initiative in international peer-reviewed journals and at medical conferences. TRIAL REGISTRATION NUMBER: NCT03908086.

Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: Observational Data From the Danish DANBIO Registry Emulating a Randomized Trial.

OBJECTIVE: Nationwide Danish guidelines regarding rheumatoid arthritis (RA) patients initiating biologic treatment (i.e., biologic disease-modifying antirheumatic drugs [DMARDs]) are issued on an approximately annual basis. For biologics-naive patients treated with concomitant methotrexate, mandatory medications included certolizumab pegol (CZP; year 2013-2014, recommended compliance 80%), abatacept (ABA; 2014-2015, 80%), and biosimilar infliximab (CT-P13; 2015-2016, 50%). We hypothesized that these guidelines could be perceived as a surrogate randomization tool in which calendar period rather than patient-specific factors defined the choice of the biologic DMARD. We undertook this study to assess compliance with guidelines (supporting the assumption of surrogate randomization) and to compare the effectiveness of CZP, ABA, and CT-P13 in patients treated according to guidelines. METHODS: This was an observational cohort study emulating a randomized trial (using intent-to-treat analyses). RA patients compliant with the treatment guidelines were identified in DANBIO, and information on prior comorbidities was obtained by linking to national registries. Outcome measures included remission rates according to the Disease Activity Score in 28 joints (DAS28) (at 6 and 12 months) and treatment retention at 1 year, compared across treatment regimens. Comorbidity/confounder-adjusted multivariable logistic and Cox regression analyses were used. RESULTS: Seven hundred seventy-six patients were included in the study (336 receiving CZP, 215 receiving ABA, 225 receiving CT-P13). Compliance with treatment guidelines was high: 70%, 65%, and 59%, respectively. Six-month DAS28 remission rates were 35%, 33%, and 42%, and 12-month rates were 35%, 31%, and 35%, respectively. Compared to CZP, adjusted odds ratios for 6- and 12-month DAS28 remission rates were 0.96 (95% confidence interval [95% CI] 0.63-1.47) and 0.74 (95% CI 0.47-1.15) for ABA and 1.38 (95% CI 0.91-2.09) and 0.96 (95% CI 0.62-1.49) for CT-P13, respectively. Adjusted hazard ratios for withdrawal (during days 0-90 and days 91-365) were 0.70 (95% CI 0.39-1.27) and 1.16 (95% CI 0.84-1.60) for ABA and 0.58 (95% CI 0.33-1.10) and 0.83 (95% CI 0.59-1.17) for CT-P13, respectively, compared to CZP. CONCLUSION: The surrogate randomization procedure enabled head-to-head comparisons of CZP, ABA, and CT-P13. Although some differences in estimated effectiveness were observed across drugs, confidence intervals were wide and statistical significance was not reached.

Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden.

OBJECTIVE: To estimate (1) crude and age-and gender-adjusted incidence rates (IRs) of serious infections (SI) and (2) relative risks (RR) of SI in patients with rheumatoid arthritis (RA) initiating treatment with abatacept, rituximab or tocilizumab in routine care. METHODS: This is an observational cohort study conducted in parallel in Denmark and Sweden including patients with RA in Denmark (DANBIO) and Sweden (Anti-Rheumatic Treatment in Sweden Register/Swedish Rheumatology Quality Register) who started abatacept/rituximab/tocilizumab in 2010-2015. Patients could contribute to more than one treatment course. Incident SI (hospitalisations listing infection) and potential confounders were identified through linkage to national registries. Age- and gender-adjusted IRs of SI per 100 person years and additionally adjusted RRs of SI during 0-12 and 0-24 months since start of treatment were assessed (Poisson regression). Country-specific RRs were pooled using inverse variance weighting. RESULTS: We identified 8987 treatment courses (abatacept: 2725; rituximab: 3363; tocilizumab: 2899). At treatment start, rituximab-treated patients were older, had longer disease duration and more previous malignancies; tocilizumab-treated patients had higher C reactive protein. During 0-12 and 0-24 months of follow-up, 456 and 639 SI events were identified, respectively. The following were the age- and gender-adjusted 12-month IRs for abatacept/rituximab/tocilizumab: 7.1/8.1/6.1 for Denmark and 6.0/6.4/4.7 for Sweden. The 24-month IRs were 6.1/7.5/5.2 for Denmark and 5.6/5.8/4.3 for Sweden. Adjusted 12-month RRs for tocilizumab versus rituximab were 0.82 (0.50 to 1.36) for Denmark and 0.76 (0.57 to 1.02) for Sweden, pooled 0.78 (0.61 to 1.01); for abatacept versus rituximab 0.94 (0.55 to 1.60) for Denmark and 0.86 (0.66 to 1.13) for Sweden, pooled 0.88 (0.69 to 1.12); and for abatacept versus tocilizumab 1.15 (0.69 to 1.90) for Denmark and 1.14 (0.83 to 1.55) for Sweden, pooled 1.13 (0.91 to 1.42). The adjusted RRs for 0-24 months were similar. CONCLUSION: For patients starting abatacept, rituximab or tocilizumab, differences in baseline characteristics were seen. Numerical differences in IR of SI between drugs were observed. RRs seemed to vary with drug (tocilizumab < abatacept < rituximab) but should be interpreted with caution due to few events and risk of residual confounding.

To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry.

OBJECTIVES: Real-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised. METHODS: Observational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted). RESULTS: 1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months' preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers' clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective. CONCLUSION: Seventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

Colonoscopy-related complications in a nationwide immunochemical fecal occult blood test-based colorectal cancer screening program.

BACKGROUND: The Danish national screening program for colorectal cancer (CRC) consists of an immunochemical fecal occult blood test (iFOBT) followed by colonoscopy. The Danish Colorectal Cancer Screening Database (DCCSD) records data on the incidence of hospital-registered complications after colonoscopy. However, the validity of these data is unknown, and the incidence of complications is potentially underreported. OBJECTIVE: To evaluate the validity of the colonoscopy complications registered in the DCCSD by using medical records as the reference. Further, to evaluate the incidence of complications leading to hospital contact. METHODS: Among 14,671 individuals with a positive iFOBT result and a colonoscopy procedure performed from March 3, 2014 to December 31, 2014, we selected 295 individuals for medical record review. We calculated sensitivity as the proportion of true complications registered in the DCCSD out of all complications found in the medical records, and the positive predictive value (PPV) as the number of true complications in the DCCSD out of all DCCSD-registered complications. On the basis of the medical record data, we calculated the incidence proportion of hospital-registered complications overall and by subtype. RESULTS: In total, we reviewed 286 records and found 102 individuals with at least one complication. The sensitivity of the DCCSD for any complication was 29.4% (95% CI: 20.8-39.3) and the PPV was 88.2% (95% CI: 72.6-96.7). On the basis of the medical record data, the incidence proportion of any complication after colonoscopy was 0.70% (95% CI: 0.57-0.84) and that of perforation or lesion was 0.10% (95% CI: 0.06-0.17); bleeding, 0.41% (95% CI: 0.31-0.53); post-polypectomy syndrome, 0.16% (95% CI: 0.10-0.24); and other medical complications, 0.04 (95% CI: 0.02-0.09). CONCLUSION: The DCCSD has low sensitivity for complications, and improvements in data registration are warranted. The incidence proportion of any hospital-treated post-colonoscopy complication was 0.70% in 2014, which was the first year of the Danish national CRC screening program. This is within the range of complications reported by other studies.

Cervical screening in Denmark - a success followed by stagnation.

INTRODUCTION: Despite an intensive screening activity, the incidence of cervical cancer in Denmark has remained stable for the last 15 years, while regional differences have increased. To search for explanations, we investigated possible weaknesses in the screening program. MATERIAL AND METHODS: Data on the screen-targeted women were retrieved from Statistics Denmark. Data on screening activity were retrieved from the annual reports from 2009 to 2015 on quality of cervical screening. Coverage was calculated as proportion of screen-targeted women with at least one cytology sample within recommended time intervals. Insufficient follow-up was calculated as proportion of abnormal and unsatisfactory samples not followed up within recommended time intervals. Diagnostic distribution was calculated for samples with a satisfactory cytology diagnosis. RESULTS: Coverage remained stable at 75%-76% during the study period. Annually, approximately 100,000 women are screened before they are eligible for invitation, and 600,000 invitations and reminders are issued resulting in screening of 200,000 women. In 2009, 21% of abnormal and unsatisfactory samples were not followed up within the recommended time interval; a proportion that had decreased to 15% in 2015. Overall, 11% of satisfactory samples with a cytology diagnosis were abnormal, but with surprising variation from 6% to 15% across regions. DISCUSSION: The success of a screening program depends first of all on coverage and timely follow-up of abnormal findings. Our analysis indicated that the currently high incidence of cervical cancer in Denmark may partly be due to low screening coverage. Also worrisome is a high proportion of non-timely follow-up of abnormal findings. Innovative ways to improve coverage and follow-up are urgently needed.

Severe Mental Illness and Clinical Outcome After Primary Percutaneous Coronary Intervention.

The mechanisms behind the increased mortality in patients with acute myocardial infarction and co-existing severe mental illness (SMI) compared with non-SMI patients remain unclear. We studied 12,102 patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention, of whom 457 had SMI. The primary outcome was major adverse cardiac events (death, myocardial infarction, target vessel revascularization) at 30 days, 1 year, 2 years, and maximum follow-up. Patients with SMI were younger, more often women, had higher prevalence of active smoking and diabetes, and had a longer duration of symptoms than patients without SMI. There were no substantial differences in the in-hospital treatment of patients with and without SMI. Fewer SMI patients were treated with the recommended medications during follow up; however, the absolute differences were modest. Compared with non-SMI patients, the cumulative risks of major adverse cardiac events after 1 year, 2 years, and maximum follow-up were higher among SMI patients [hazard ratio 1.27 (1.02 to 1.57), hazard ratio 1.32 (1.09 to 1.60), and hazard ratio 1.43 (1.25 to 1.65), respectively]. Even after adjustment for differences in baseline characteristics, the differences in outcome persisted. In conclusion, compared with patients without SMI, primary percutaneous coronary intervention treated patients with SMI had a worse baseline risk profile. No differences in in-hospital treatments were found. Although the absolute differences were small, SMI patients were less likely to receive recommended medical treatment during follow up and they face a worse prognosis, even after adjustment for differences in risk profile. This indicates that SMI per se is likely to have an adverse effect on the prognosis following ST-elevation myocardial infarction.

Lifetime Risk of Primary Total Hip Replacement Surgery for Osteoarthritis From 2003 to 2013: A Multinational Analysis Using National Registry Data.

OBJECTIVE: To compare the lifetime risk of total hip replacement (THR) surgery for osteoarthritis (OA) between countries, and over time. METHODS: Data on primary THR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway, and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of THR was calculated for 2003 and 2013 using registry, life table, and population data. RESULTS: In 2003, lifetime risk of THR ranged from 8.7% (Denmark) to 15.9% (Norway) for females, and from 6.3% (Denmark) to 8.6% (Finland) for males. With the exception of females in Norway (where lifetime risk started and remained high), lifetime risk of THR increased significantly for both sexes in all countries from 2003 to 2013. In 2013, lifetime risk of THR was as high as 1 in 7 women in Norway, and 1 in 10 men in Finland. Females consistently demonstrated the highest lifetime risk of THR at both time points. Notably, lifetime risk for females in Norway was approximately double the risk for males in 2003 (females 15.9% [95% confidence interval (95% CI) 15.6-16.1], males 6.9% [95% CI 6.7-7.1]), and 2013 (females 16.0% [95% CI 15.8-16.3], males 8.3% [95% CI 8.1-8.5]). CONCLUSION: Using representative, population-based data, this study found statistically significant increases in the lifetime risk of THR in 5 countries over a 10-year period, and substantial between-sex differences. These multinational risk estimates can inform resource planning for OA service delivery.

The database of the Danish Renal Cancer Group.

AIM OF THE DATABASE: The main purpose of the database of the Danish Renal Cancer Group (DaRenCaData) is to improve the quality of renal cancer treatment in Denmark and secondarily to conduct observational research. STUDY POPULATION: DaRenCaData includes all Danish patients with a first-time diagnosis of renal cancer in the Danish National Pathology Registry since August 1, 2010. MAIN VARIABLES: DaRenCaData holds data on demographic characteristics, treatments, and pathology collected through linkage to central registries and online registration of a few clinical key variables. Eight quality indicators have been selected for monitoring treatment quality and outcome after renal cancer. DESCRIPTIVE DATA: The incidence of renal cancer in Denmark has increased from 12.7 per 100,000 population-years in 2010-2011 to 15.9 per 100,000 population-years in 2014-2015. A total of 3,977 Danish patients with renal cancer have been enrolled in the database in the period August 1, 2010-July 31, 2015. The completeness of data registration has increased substantially since the first years of the database. A tendency toward smaller and less advanced tumors, less invasive surgery, and a shorter hospital stay was observed, while the postoperative morbidity and mortality remained stable. Concurrently, the 1-year survival has improved and was 84.1% in 2014-2015. CONCLUSION: DaRenCaData provides valuable information on quality of and outcome after renal cancer treatment. Efforts to improve collection and registration of data are ongoing.

Age- and sex-related differences in use of guideline-recommended care and mortality among patients with incident heart failure in Denmark.

BACKGROUND: data are sparse on age- and sex-related differences in use of guideline-recommended care and subsequent mortality among patients with heart failure (HF). METHODS: we identified 24,308 incident patients with a verified primary diagnosis of HF recorded during 2003-2010 in the Danish Heart Failure Registry. The registry monitors guideline-recommended processes of care: echocardiography, New York Heart Association Classification, treatment with angiotensin converting enzyme inhibitors/angiotensin II receptor blockers, betablockers, physical training and patient education. RESULTS: older age was associated with lower use of recommended processes of care. Relative risk (RR) for receiving processes of care varied for men >80 years from 0.52 to 0.91 compared with men ≤65 years. Corresponding RRs among women >80 years varied from 0.55 to 0.89 compared with women ≤65 years. Older age was as expected associated with higher 1 year mortality (32.6% among men >80 years versus 5.4% among men ≤65 years and 33.8% among women >80 years versus 6.6% among women ≤65 years). The corresponding hazard ratios (HRs) were 4.54 (95% CI 3.93-5.25) and 4.08 (95% CI 3.51-4.75) for the oldest versus youngest men and women, after adjustment for patient characteristics. Adjustment for differences in care lowered HRs among the oldest age groups (adjusted HR 3.87 for men and 3.48 for women, respectively). The findings were also confirmed when stratifying the patients according to left ventricular ejection fraction ≤40% and >40%. CONCLUSION: older patients with HF were less likely to receive guideline-recommended processes of care, irrespective of sex. Lower level of care may contribute to an excess mortality observed among the older patients.

Rheumatoid Arthritis: Trends in Antirheumatic Drug Use, C-reactive Protein Levels, and Surgical Burden.

OBJECTIVE: Over the past decade, the therapeutic approach used to treat patients with rheumatoid arthritis (RA) has considerably changed. It remains unclear whether these changes have been accompanied by decreased disease severity and surgical treatment burden at the population level. Therefore, we investigated time trends in antirheumatic drug consumption, C-reactive protein (CRP) levels, and use of orthopedic surgery among Danish patients with RA. METHODS: Using medical databases, we identified all patients with RA living in Northern Denmark during 1996-2012. For each calendar year, we computed the annual rate of antirheumatic drug use (1996-2010), the median CRP value in mg/l (1996-2011), and the proportions of patients who underwent hip replacement and other orthopedic procedures (1996-2012). RESULTS: Antirheumatic drug consumption per patient increased 5-fold, from 145.0 defined daily doses (DDD) in 1996 to 695.4 DDD in 2010. Median CRP declined from 20.5 mg/l [interquartile range (IQR), 10.0 to 43.5 mg/l] in 1996 to 10.0 mg/l (IQR, 4.2-17.8 mg/l) in 2011. From 1996 to 2012, declining proportions of patients with RA underwent hip replacement (14.9% to 10.1%) and other joint operations (29.1% to 23.4%), while the annual proportion of patients who underwent soft tissue procedures increased from 20.7% to 23.4%. CONCLUSION: Antirheumatic drug consumption has substantially increased among patients with RA since 1996, in association with reduced disease activity (i.e., lower CRP levels), fewer joint procedures (including hip replacements), and more soft tissue procedures.