Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Exercise and education vs intra-articular saline for knee osteoarthritis: a 1-year follow-up of a randomized trial.

OBJECTIVE: To assess the longer-term effect of the Good Life with osteoarthritis in Denmark (GLAD) exercise and education program relative to open-label placebo (OLP) on changes from baseline in core outcomes in individuals with knee osteoarthritis (OA). METHODS: In this 1-year follow-up of an open-label, randomized trial, patients with symptomatic and radiographically confirmed knee OA were monitored after being randomized to either the 8-week GLAD program or OLP given as 4 intra-articular saline injections over 8 weeks. The primary outcome was the change from baseline in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale after 1 year in the intention-to-treat population. Key secondary outcomes were the KOOS function and quality of life subscales, and Patients' Global Assessment of disease impact. RESULTS: 206 adults were randomly assigned: 102 to GLAD and 104 to OLP, of which only 137 (63/74 GLAD/OLP) provided data at 1 year. At one year the mean changes in KOOS pain were 8.4 for GLAD and 7.0 for OLP (Difference: 1.5 points; 95% CI -2.6 to 5.5). There were no between-group differences in any of the secondary outcomes. CONCLUSIONS: In this 1-year follow-up of individuals with knee OA, the 8-week GLAD program and OLP both provided minor longer-term benefits with no group difference. These results require confirmation given the significant loss to follow-up. TRIAL REGISTRATION NUMBER: NCT03843931.

Increased prevalence of sleep disturbance in psoriatic arthritis is associated with inflammatory and non-inflammatory measures.

OBJECTIVES: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI. METHOD: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures. RESULTS: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment. CONCLUSION: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA.Trial registration: ClinicalTrials.gov (NCT02572700).

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial.

OBJECTIVE: To identify contextual factors that modify the treatment effect of the 'Good Life with osteoArthritis in Denmark' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). METHODS: Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. RESULTS: Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). CONCLUSIONS: These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.

The effect of risankizumab on achieving minimal clinically important differences in patient-reported outcomes in patients with psoriatic arthritis: results from KEEPsAKE 1 and 2.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that reduces the quality of life. This study assessed the effects of risankizumab (RZB) on the achievement of minimal clinically important differences (MCID) in patient-reported outcomes (PROs). METHODS: KEEPsAKE-1 and -2 are randomized, placebo-controlled Phase 3 clinical studies assessing RZB (150 mg) vs. placebo (PBO) in adult patients with PsA with inadequate response or intolerance to disease-modifying antirheumatic drugs and/or biologics. Patients were randomized 1:1 to receive RZB or PBO for 24 weeks; starting at Week 24, all patients received RZB 150 mg through Week 52. PROs assessed were Patient's Global Assessment of Disease Activity (PtGA), Patient's Assessment of Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form 36 Physical and Mental Component Summary scores (PCS and MCS, respectively), 5-Level EQ-5D (EQ-5D-5L), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Work Productivity and Activity Impairment (WPAI). The proportion of patients achieving MCID at Weeks 24 and 52 are reported. Odds ratios of achieving MCID with RZB treatment at Week 24, relative to PBO, were estimated by logistic regression controlling for baseline and stratification factors. RESULTS: In KEEPsAKE-1, RZB- vs. PBO-treated patients were more likely to report MCID in all PROs at Week 24; similar results were obtained in KEEPsAKE-2, except for SF-36 MCS and WPAI presenteeism domain. In KEEPsAKE-1 and KEEPsAKE-2, 65% and 62% of RZB-treated patients, respectively, reported MCID in PtGA at Week 24, which increased to 74% and 68%, respectively, at Week 52. Approximately 48% of all PBO-treated patients reported MCID in PtGA at Week 24 and, after initiating RZB, >65% reported MCID at Week 52. Results were similar in the remaining PROs. CONCLUSIONS: These data demonstrate that patients with PsA receiving RZB treatment are more likely to report clinically important improvements in PROs compared with patients receiving PBO.

PET in vivo generators 134Ce and 140Nd on an internalizing monoclonal antibody probe.

The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.

Agreement between self-reported and observed functioning in patients with rheumatoid arthritis, osteoarthritis, and fibromyalgia, and the influence of pain and fatigue: a cross-sectional study.

OBJECTIVE: To evaluate the relationship between self-reported and performance-based measures of functioning in rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and the influence of pain and fatigue. METHOD: Self-reported functioning was assessed by the Stanford Health Assessment Questionnaire, Fibromyalgia Impact Questionnaire, and Knee injury and Osteoarthritis Outcome Score. Performance-based measures of task-related physical activity included grip strength and Six-Minute Walk Test (6MWT). Assessment of Motor and Process Skills (AMPS) was used to obtain performance-based measures of activities of daily living (ADL) ability. Pain and fatigue were assessed by 100 mm visual analogue scales. Spearman's rho correlation and regression modelling were applied. RESULTS: Correlations between self-reported functioning and performance-based measures of ADL ability were weak to moderate, and strongest in OA (r = 0.57, p = 0.002), and AMPS ADL ability measures did not enter regression models as explanatory factors for self-reported functioning. Correlations between AMPS ADL ability measures and measures of task-related physical activity were weak, except for a strong correlation between AMPS ADL motor ability and 6MWT in OA (r = 0.63, p = 0.000). The 6MWT was the only performance-based test explaining variance in AMPS motor ability (OA = 42%; FM = 11%). Pain explained variance in self-reported ability and contributed to variance in AMPS ADL motor ability measures in OA. CONCLUSION: Self-reported and observed measures of functioning assess partly different aspects of functioning, and both approaches may therefore be relevant in a structured assessment of patients with musculoskeletal disorders.

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study.

OBJECTIVES: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries. METHODS: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment. RESULTS: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association. CONCLUSION: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.

Multicentric Analysis of the Species Distribution and Antifungal Susceptibility of Cryptic Isolates from Aspergillus Section Fumigati.

The antifungal susceptibility of Aspergillus cryptic species is poorly known. We assessed 51 isolates, belonging to seven Fumigati cryptic species, by the EUCAST reference method and the concentration gradient strip (CGS) method. Species-specific patterns were observed, with high MICs for azole drugs, except for Aspergillus hiratsukae and Aspergillus tsurutae, and high MICs for amphotericin B for Aspergillus lentulus and Aspergillus udagawae Essential and categorical agreements between EUCAST and CGS results were between 53.3 and 93.3%.

Absence of colon as the predominant risk factor for liver fibrosis in adults requiring home parenteral nutrition.

BACKGROUND: Liver fibrosis is a well-known complication of long-term use of parenteral nutrition in patients with intestinal failure associated to the nutrient composition in parenteral nutrition. This study investigates the prevalence of significant liver fibrosis and identifies risk factors for liver fibrosis. METHODS: This was a retrospective study of 35 parenteral nutrition-dependent patients with intestinal failure and 54 patients with intestinal insufficiency and oral nutrition only with a valid liver stiffness measurement obtained with transient elastography from November 2016 to August 2018. Clinical and demographic parameters including age, fat mass index and fat-free mass index, intact colon or colectomy, and nutritional management were analyzed for their association with liver stiffness. RESULTS: A prevalence for liver fibrosis (liver stiffness >7.0 kPa) was established at 37.1% in parenteral nutrition-dependent patients and at 22.2% in patients on oral nutrition. Several factors were significantly and independently associated with liver fibrosis including lipids in home parenteral nutrition (OR 10.66, p = 0.010) and colectomies (OR 3.24, p = 0.036). CONCLUSION: More than a third of patients receiving home parenteral nutrition have liver fibrosis. Several risk factors were demonstrated such as the amount of lipids and performed colectomies despite current international guidelines for lipids are followed. Our findings emphasize suggest a new perspective to prevent significant hepatic complications: colectomies.

Realization of efficient quantum gates with a superconducting qubit-qutrit circuit.

Building a quantum computer is a daunting challenge since it requires good control but also good isolation from the environment to minimize decoherence. It is therefore important to realize quantum gates efficiently, using as few operations as possible, to reduce the amount of required control and operation time and thus improve the quantum state coherence. Here we propose a superconducting circuit for implementing a tunable system consisting of a qutrit coupled to two qubits. This system can efficiently accomplish various quantum information tasks, including generation of entanglement of the two qubits and conditional three-qubit quantum gates, such as the Toffoli and Fredkin gates. Furthermore, the system realizes a conditional geometric gate which may be used for holonomic (non-adiabatic) quantum computing. The efficiency, robustness and universality of the presented circuit makes it a promising candidate to serve as a building block for larger networks capable of performing involved quantum computational tasks.

Cause-specific mortality in patients with psoriasis and psoriatic arthritis.

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA). OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA. METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA. RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001). CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.

High incidence of candidaemia in a nationwide cohort: Underlying diseases, risk factors and mortality.

BACKGROUND: Denmark has a high incidence rate of candidaemia. A Nordic study suggested a higher Danish prevalence of haematological malignancies as an underlying reason. This nationwide study ascertained clinical characteristics of Danish candidaemia patients and investigated potential factors contributing to the high incidence and mortality. METHODS: Microbiological and clinical data for candidaemia patients in 2010-2011 were retrieved. 30-day mortality was estimated by hazard ratios (HR) with 95% confidence intervals (CI, Cox regression). RESULTS: Data were available for 912/973 candidaemia episodes (93.7%). Intensive care unit (ICU) held the largest share of patients (43.2%). Prevalent host factors were multi-morbidity (≥2 underlying diseases, 74.2%) and gastrointestinal disease (52.5%). Haematological disease was infrequent (7.8%). Risk factors included antibiotic exposure (90.5%), CVC (71.9%) and Candida colonisation (66.7%). 30-day mortality was 43.4%, and 53.6% in ICU. Mortality was lower for patients with recent abdominal surgery (HR 0.70, 95% CI: 0.54-0.92). CONCLUSION: A substantial prevalence of multi-morbidity and a high 30-day mortality was found. We hypothesise, that an increasing population of severely ill patients with prolonged supportive treatment and microbiological testing may in part explain the high candidaemia incidence in Denmark. Nationwide studies are warranted to clarify this issue.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries.

OBJECTIVES: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. METHOD: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. RESULTS: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). CONCLUSION: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Burden of rheumatoid arthritis in the Nordic region, 1990-2015: a comparative analysis using the Global Burden of Disease Study 2015.

OBJECTIVE: To report mortality and disability due to rheumatoid arthritis (RA) in the Nordic region (Denmark, Finland, Greenland, Iceland, Norway, and Sweden) using data from the Global Burden of Disease Study (GBD) 2015. METHOD: Using the results of GBD 2015, we present rates and trends in prevalence, mortality, years of life lost, years lived with disability (YLD), and disability-adjusted life-years (DALYs) of RA in the Nordic region during 1990-2015. RESULTS: In 2015, the age-standardized prevalence of RA was higher in the Nordic region than the global level (0.44%, 95% uncertainty interval 0.40-0.48%, vs 0.35%, 0.32-0.38%). For women (men), DALYs increased by 2.4% (12.9%), from 29 263 (10 909) in 1990 to 29 966 (12 311) in 2015. The burden of RA as a proportion of total DALYs in women (men) increased from 0.90% (0.29%) in 1990 to 0.94% (0.36%) in 2015. Age-standardized DALY rates declined in all countries except Denmark and Greenland between 1990 and 2015. Of 315 conditions studied, RA was ranked as the 16th (37th) leading cause of YLD in women (men) in the region. Of 195 countries studied, Greenland, Finland, Denmark, Norway, Sweden, and Iceland had the 7th, 11th, 28th, 38th, 48th, and 78th highest age-standardized YLD rates for RA, respectively. CONCLUSIONS: The prevalence of RA in the Nordic region is higher than the global average. Current trends in population growth and ageing suggest a potential increase in RA burden in the coming decades in the region that should be considered in healthcare resources allocation.

Circular RNAs in cancer: opportunities and challenges in the field.

Circular RNA (circRNA) is a novel member of the noncoding cancer genome with distinct properties and diverse cellular functions, which is being explored at a steadily increasing pace. The list of endogenous circRNAs involved in cancer continues to grow; however, the functional relevance of the vast majority is yet to be discovered. In general, circRNAs are exceptionally stable molecules and some have been shown to function as efficient microRNA sponges with gene-regulatory potential. Many circRNAs are highly conserved and have tissue-specific expression patterns, which often do not correlate well with host gene expression. Here we review the current knowledge on circRNAs in relation to their implications in tumorigenesis as well as their potential as diagnostic and prognostic biomarkers and as possible therapeutic targets in future personalized medicine. Finally, we discuss future directions for circRNA cancer research and current caveats, which must be addressed to facilitate the translation of basic circRNA research into clinical use.

Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and Acquired Resistance Causes Concern.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of Candida albicans isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001), and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively, P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

Pain and pain mechanisms in patients with inflammatory arthritis: A Danish nationwide cross-sectional DANBIO registry survey.

BACKGROUND: Central pain mechanisms may be prominent in subsets of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis (SpA). The painDETECT questionnaire (PDQ) identifies neuropathic pain features, which may act as a proxy for centrally mediated pain. The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. METHODS: The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology in Denmark for six months. Clinical data and patient reported outcomes were obtained from DANBIO. A PDQ-score >18 indicated neuropathic pain features, 13-18 unclear pain mechanism and <13 non-neuropathic pain. RESULTS: Pain data (visual analogue scale, VAS) was available for 15,978 patients. 7,054 patients completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (<13/ 13-18/ >18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18 compared to RA and SpA (p<0.001). For PDQ > 18 significantly higher scores were found for all patient reported outcomes and disease activity scores. No clinical difference in CRP or swollen joint count was found. Logistic regression showed increased odds for having VAS pain ≥39 mm (the median) for a PDQ-score >18 compared to <13 (OR = 10.4; 95%CI 8.6-12.5). CONCLUSIONS: More than 50% of the Danish arthritis patients reported clinically significant pain. More than 20% of the PDQ-completers had indication of neuropathic pain features, which was related to a high pain-level. PDQ-score was associated with DAS28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment.

Left ventricular function at two-year follow-up in treatment-naive rheumatoid arthritis patients is associated with anti-cyclic citrullinated peptide antibody status: a cohort study.

OBJECTIVES: In rheumatoid arthritis (RA), the role of autoimmunity, especially anti-cyclic citrullinated peptide antibody (anti-CCP) level, and the time-course of left ventricular (LV) function is unknown. The objective was to assess LV function and the amount of coronary calcium in relation to anti-CCP levels in a cohort of treatment-naive RA patients, and to assess changes in these parameters during a 2 year follow-up period. METHOD: Sixty-six steroid- and disease-modifying anti-rheumatic drug-naive RA patients were treated with methotrexate according to the Danish national guidelines. We assessed LV function by conventional echocardiography and speckle-tracking echocardiography. We estimated the amount and progression of coronary calcium by coronary computed tomography. Patients were examined at the time of diagnosis and after 2 years. RESULTS: Patients with elevated anti-CCP at baseline and after 2 years, compared to those with non-persistently elevated anti-CCP, had significantly less improvement in S´ (1 ± 1.4 cm/s vs 0.2 ± 0.9 cm/s; p = 0.04) and a worsening in global longitudinal systolic strain (GLS) (0.6 ± 1.8% vs -1 ± 2.8%; p = 0.04). There was a significant correlation between ΔGLS over 2 years and anti-CCP at 2 year follow-up (r = 0.36; p = 0.006). We observed a small progression of coronary calcium score during the 2 year follow-up period. No differences in progression were found between patients with high anti-CCP titres at baseline and 2 year follow-up (n = 12) and patients with normal/low anti-CCP titres (n = 32) (23.8 ± 40.3 vs 22.6 ± 68.9; p = 0.96). CONCLUSIONS: Deformation analysis by speckle-tracking echocardiography is a valuable tool to detect early development of myocardial dysfunction despite normal ejection fraction in RA.