Introduction: Oral anticoagulants in patients with atrial fibrillation (AF) with moderate-to-high stroke risk are strongly recommended by the current guidelines.Materials and methods: Population-based register study of all 13,837 patients with incident non-valvular AF diagnosed during 2011-2014 in primary and secondary care (including all in-and outpatient visits) in Skane County, Sweden. The outcome was the prescription of direct-acting oral anticoagulants (DOAC), warfarin or acetylsalicylic acid (ASA).Results and conclusion: Guideline adherence increased from 47.6% in 2011 to 66.1% in 2014, mostly due to decrease in undertreatment. In patients with CHA(2)DS(2)-VASc score >= 2, ASA uptake decreased from 29.9% to 14.7% and DOAC uptake increased from 2.1% to 25.1%. The use of ASA was more common among elderly and with increasing stroke-and bleeding risk. Overall, 47.4% of patients with CHA(2)DS(2)-VASc score >= 2 did not receive oral anticoagulants. Undertreatment was particularly common in women < 65 years (55.8%) and in patients >84 years (65.3% in women and 62% in men). Overtreatment of patients at low stroke risk was 35.9% in men and 36.4% in women. Provider speciality affected the choice of treatment only to a minor degree. Despite increasing guideline adherence, there is a suboptimal use of antithrombotic therapy in a large proportion of AF patients diagnosed in different clinical settings. Efforts to further improve guideline adherence should particularly be targeted on women < 65 years, elderly > 84 years and patients at low stroke risk. (C) 2016 Elsevier Ltd. All rights reserved.

Background Low socioeconomic status (SES), measured through a variety of ways (e.g. formal education, occupation, household income, ethnicity) has been associated with an increased risk of rheumatoid arthritis (RA), an elevated economic burden for patients and society, as well as a worse disease outcome. Objectives To investigate the effect of educational status (achieving a university/college degree) on the prognosis of RA overall, as well as on disease subsets based on ACPAs, in terms of DAS28, physician assessment, VAS-pain, and HAQ. Methods We used cases from the population-based EIRA study with outcomes followed-up in the Swedish Rheumatology Quality Register (N=3021). We categorized the outcomes in different ways: 1) having equal to/above vs. below median levels; 2) achieving low disease activity, good response, and remission vs. not achieving; 3) having scores decreased over the median vs. less than median. We calculated the ORs of those outcome categories as an effect of higher education, both at diagnosis and for the first three follow-up visits (3, 6, 12 months). Results We found patients of higher education initiated with less pain and less functional disability (VAS-pain: 49 (28-67) vs. 53 (33-71), p<0.0001, HAQ: 0.88 (0.50-1.38) vs. 1.00 (0.63-1.50), p=0.001). The effects persisted across the follow-up period. They had greater chances to achieve pain remission (3-month-visit: 1.35 (1.08-1.69); 6-month-visit: 1.22 (0.95-1.56); 1-year-visit: 1.23 (1.00-1.52)) and improve to a larger extent (HAQ decrease over the median: 3-month-visit: 1.45 (1.13-1.86); 6-month-visit: 1.41 (1.07-1.86); 1-year-visit: 1.43 (1.12-1.82)). Conclusions Higher educated patients experienced less pain and less functional disability starting from baseline throughout the first year receiving standard care; they achieved pain remission more and attain greater improvements on physical function as compared to less educated patients. We could not identify any distinct effects of educational background on disease activity related outcomes. Disclosure of Interest None declared

Whether low socioeconomic status (SES) is associated with worse rheumatoid arthritis (RA) outcomes in countries with general tax-financed healthcare systems (such as Sweden) remains to be elucidated. Our aim was to investigate the influence of educational background (achieving university/college degree (high) or not (low)) on the outcomes of early RA, in terms of disease activity (DAS28), pain (VAS-pain), and functional impairment (HAQ).

Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.

Objectives Do recent infections affect the risk of rheumatoid arthritis (RA)?Methods We used the population-based case-control study EIRA (N= 6401) on incident RA and healthy controls, matched for sex, age, calendar period and area of residence. Gastroenteritis, urinary tract infection, genital infection, prostatitis, sinusitis, tonsillitis and pneumonia during the 2 years before inclusion in the study were investigated. Conditional logistic regression was used to calculate OR, adjusting for smoking and socioeconomic status.Results Infections in the gastrointestinal and urogenital tract before clinical onset were associated with a lowered risk of RA: gastroenteritis (OR= 0.71 (95% CI 0.63 to 0.80)), urinary tract infections (OR= 0.78 (95% CI 0.68 to 0.90)) and genital infections (OR= 0.80 (95% CI 0.64 to 1.00)), while a non-significant association of similar magnitude was observed for the less common prostatitis (OR= 0.64 (95% CI 0.38 to 1.08)). In contrast, no associations were observed for sinusitis, tonsillitis or pneumonia.Conclusions Gastrointestinal and urogenital infections, but not respiratory infections, are associated with a significantly lowered risk of RA. The results indicate that infections in general do not affect the risk for RA, but that certain infections, hypothetically associated with changes in the gut microbiome, could diminish the risk.

Response to: 'Obesity and comorbidity are independently associated with a failure to achieve remission in patients with established rheumatoid arthritis' by Ellerby et alWe thank Ellerby et al 1 for their interest in our manuscript addressing the effect of obesity on the prognosis of rheumatoid arthritis (RA), and for sharing their own data.We are happy to see Ellerby and colleagues' findings in the later phase of RA to be in accordance with our own findings in early RA, 2 and to confirm findings by Ajeganova et al 3 who have shown a similar effect of obesity in patients with longstanding RA.We are, as Ellerby and colleagues are, also very interested in the underlying biological mechanism for these findings.Further, we look forward to upcoming initiatives to clinically study whether this link between obesity and decreased chance of good response and remission can be countered by a voluntary weight decrease during the disease course.

AIM:To investigate whether overweight/obesity at diagnosis affects the chances of decrease in disease activity and pain in early rheumatoid arthritis (RA). METHOD:We investigated incident RA cases from the population-based Epidemiological Investigation of risk factors for Rheumatoid Arthritis (EIRA) study (2006-2009, N=495) with clinical follow-up in the Swedish Rheumatology Quality Register. At diagnosis, 93% received disease-modifying antirheumatic drugs (DMARDs) (86% methotrexate). The odds of achieving a good response according to the DAS28-based European League Against Rheumatism (EULAR) criteria, low disease activity (DAS28<3.2), remission (DAS28<2.6) or pain remission (visual analogue scale ≤20 mm) at 3-months and 6-months follow-up, were calculated using logistic regression, adjusting for potential confounders. RESULTS:Significant dose-response relationships were found between Body Mass Index (BMI) and change of disease activity as well as pain at both time points. Patients with BMI ≥25 had 51% lower odds of achieving low disease activity (odds ratio (OR=0.49 (95% CI 0.31 to 0.78)) and 42% lower odds of remission (OR=0.58 (95% CI 0.37 to 0.92)) at the 6-months visit, compared to normal-weight patients. This effect was also present at 3 months, where we also found a 43% decreased odds of pain remission (OR=0.57 (95% CI 0.37 to 0.88)). No effect modification was found for anti-citrullinated protein antibody (CCP)-status, sex, prednisolone treatment or DAS28 at diagnosis. CONCLUSIONS:Overweight at diagnosis significantly decreases the chance of achieving good disease control during the early phase of RA.

Objectives Physical activity has been shown to decrease inflammatory markers; here we investigate the effect on the clinical presentation of rheumatoid arthritis (RA).Methods We used the cases from the population-based EIRA study (N=617), followed in the Swedish Rheumatology Quality Register, calculating the odds of having above median level of 28-joint disease activity score (DAS28), physician assessment, pain (visual-analogue scale (VAS), VAS-pain) and activity limitation (health assessment questionnaire (HAQ)) at diagnosis, as an effect of physical activity 5 years before diagnosis, investigated both in categories and dichotomised.Results Dose-response relationships were seen for all measures; the higher the level of physical activity, the lower the likelihood of having outcome measure above median. Further, regular physical activity associated with 42% reduced odds of having DAS28 above median (OR=0.58 (95% CI 0.42 to 0.81)). Effects were similar for VAS-pain (OR=0.62 (95% CI 0.45 to 0.86)) and physician assessment (OR=0.67 (95% CI 0.47 to 0.95)) but not for HAQ. Statistically significant effects were also found both for the combined objective components and the combined subjective components of DAS28.Conclusions Physically active individuals seem to present with milder RA, which adds to the evidence of beneficial effects of physical activity on inflammatory diseases. The observation should be important for both health professionals and individuals seeking to reduce their risk.

Introduction Mammographic density is a strong risk factor for breast cancer, but it is unknown whether density at first breast cancer diagnosis and changes during follow-up influences risk of non-simultaneous contralateral breast cancer (CBC). Methods We collected mammograms for CBC-patients (cases, N = 211) and unilateral breast cancer patients (controls, N = 211), individually matched on age and calendar period of first breast cancer diagnosis, type of adjuvant therapy and length of follow-up (mean follow-up time: 8.25 years). The odds of CBC as a function of changes of density during follow-up were investigated using conditional logistic regression, adjusting for non-dense area at diagnosis. Results Patients who experienced ≥10% absolute decrease in percent density had a 55% decreased odds of CBC (OR = 0.45 95% CI: 0.24 to 0.84) relative to patients who had little or no change in density from baseline to first follow-up mammogram (mean = 1.6 (SD = 0.6) years after diagnosis), whereas among those who experienced an absolute increase in percent density we could not detect any effect on the odds of CBC (OR = 0.83 95% CI: 0.24 to 2.87). Conclusion Decrease of mammographic density within the first two years after first diagnosis is associated with a significantly reduced risk of CBC, this potential new risk predictor can thus contribute to decision-making in follow-up strategies and treatment.

BACKGROUND:It is unclear whether estrogen receptor (ER)-status of first primary breast cancer is associated with risk of metachronous (non-simultaneous) contralateral breast cancer (CBC), and to what extent endocrine therapy affects this association.METHODS:We studied the effect of ER-status of the first cancer on the risk of CBC overall, and for different ER-subtypes of CBC, using a large, population-based cohort. The cohort consisted of all women diagnosed with breast cancer in the Stockholm region 1976-2005; 25715 patients, of whom 940 suffered CBC. The relative risk was analyzed mainly using standardized incidence ratios (SIR).RESULTS:Women with breast cancer had a doubled risk of CBC compared to the risk of breast cancer in the general female population (SIR: 2.22 [2.08-2.36]), for women with a previous ER-positive cancer: SIR=2.30 (95% CI:2.11-2.50) and for women with a previous ER-negative cancer: SIR=2.17 (95% CI:1.82-2.55). The relative risk of ER-positive and ER-negative CBC was very similar for women with ER-positive first cancer (SIR=2.02 [95%CI: 1.80-2.27] and SIR=1.89 [95%CI: 1.46-2.41] respectively) while for patients with ER-negative first cancer the relative risk was significantly different (SIR=1.27 [95% CI:0.94-1.68] for ER-positive CBC and SIR=4.96 [95%CI:3.67-6.56] for ER-negative CBC). Patients with ER-positive first cancer who received hormone therapy still had a significantly higher risk of CBC than the risk of breast cancer for the general female population (SIR=1.74 [95% CI:1.47-2.03]).CONCLUSION:The risk of CBC for a breast cancer patient is increased to about two-fold, compared to the risk of breast cancer in the general female population. This excess risk decreases, but does not disappear, with adjuvant endocrine therapy. Patients with ER-positive first cancers have an increased risk for CBC of both ER subtypes, while patients with ER-negative first cancer have a specifically increased risk of ER-negative CBC.

Estrogen receptor (ER) status is important for breast cancer survival, it is however unclear how prognosis of contralateral breast cancer (CBC) is affected by ER-status of the two tumors. We conducted a large, population-based study of ER-status of both tumors in CBC patients and its influence on prognosis. The cohort consisted of all women diagnosed with CBC in Stockholm, Sweden during 1976-2005, with information on ER-status from medical records (N = 933). Prognosis was modeled as incidence rates of distant metastasis via Poisson regression. The proportion of CBCs with both cancers of the same ER-status was significantly larger than expected by chance. For synchronous (simultaneous) cancers the prognosis was significantly affected by the combined ER-status of both tumors (p = 0.01). Compared to unilateral breast cancer patients the incidence rate ratio (IRR) for patients with double ER-positive tumors was 1.25 (95 % CI: 0.88-1.76), for ER-discordant tumors 2.19 (95 % CI: 1.18-4.08) and for double ER-negative tumors 3.95 (95 % CI: 1.77-8.81). For metachronous (non-simultaneous) cancers, women with double ER-positive tumors had similarly bad prognosis (IRR = 2.95; 95 % CI: 2.39-3.64) as women with double ER-negative tumors (IRR = 2.88; 95 % CI: 1.83-4.52). Both shorter time span between first and second cancer and endocrine therapy for the first cancer further worsened prognosis of women with double ER-positive metachronous CBC. For synchronous CBC patients, ER-pattern of both tumors is an important prognosticator, while among metachronous CBC patients, double ER-positive tumors confer equally bad prognosis as double ER-negative cancers. Our results indicate that this might be due to endocrine therapy resistance.

We aimed to investigate if characteristics of contralateral breast cancer (CBC) are influenced by adjuvant radiotherapy for the first breast cancer. Using information from population-based registers and medical records, we analyzed two cohorts comprising all women with CBC diagnosed >3 months after their first cancer (809 patients in Stockholm 19762005 and 750 patients in South Sweden 19772005). We used Poisson regression to calculate risk of distant metastasis after CBC, comparing patients treated and not treated with radiotherapy for the first cancer. Logistic regression was used to estimate odds ratio (OR) of more aggressive tumor characteristics in the second cancer, compared to the first. For patients with CBC in Stockholm with <5 years between the cancers radiotherapy for the first cancer conferred a nearly doubled risk of distant metastasis [incidence rate ratio (IRR) = 1.91; 95% confidence interval (CI): 1.272.88], compared to those not treated with radiotherapy. This was replicated in the South Swedish cohort [IRR = 2.12 (95% CI: 1.403.23)]. In Stockholm, we found an increased odds that, following radiotherapy, a second cancer was of more advanced TNM-stage [OR 2.16 (95% CI 1.134.11)] and higher histological grade [OR = 2.00 (95% CI 1.083.72)] compared to the first, for patients with CBC with <5 years between the cancers. No effect on any of the investigated outcomes was seen for patients diagnosed with CBC >5 years from the first cancer. In conclusion, patients diagnosed with CBC within 5 years had worse prognosis and more aggressive tumor characteristics of the second cancer, if they had received radiotherapy for their first cancer, compared to no radiotherapy.