Digital ulcers predict a worse disease course in patients with systemic sclerosis

Objective: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc. Methods: Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis. Results :3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41(1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure):3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003). Conclusions :In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival

Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study

OBJECTIVES: To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). METHODS: 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. RESULTS: During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). CONCLUSIONS: The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA

Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12\ub13 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trial

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. / Methods: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. / Results: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. / Conclusion: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis

Irradiance levels of phototherapy devices : A national study in Dutch neonatal intensive care units

Objective: The objective of this study is to determine whether irradiance levels of phototherapy (PT) devices in Dutch neonatal intensive care units (NICUs) increased between 2008 and 2013. Study Design: Irradiance of all types of PT devices, used in combination with incubators, was measured with a Dale 40 Radiometer (Fluke Biomedical, Everett, WA, USA) in all 10 Dutch NICUs. Results: Irradiance increased in seven NICUs. Median (range) irradiance increased from 9.7 (4.3-32.6) to 16.4 (6.8-41) μW cm-2 nm-1 for 24 overhead devices (P=0.004) and from 6.8 (0.8-15.6) to 22.3 (1.1-36.3) μW cm-2 nm-1 for 12 underneath devices (P=0.014). Five light-emitting diode (LED)-based devices were used in 2013 and one in 2008. The mean distance between overhead PT device and infant decreased by ∼9 cm (P<0.001). Significantly more devices delivered minimal (10 μW cm-2 nm-1) recommended irradiance levels (80 vs ∼45%; P=0.002). Conclusion: Irradiance of PT devices still varies, but has markedly improved since 2008 due to shorter distances between PT device and infant, and introduction of better performing LED-based devices

Selkeäkielisen potilasohjeen kehittäminen varfariinihoitoa saavalle potilaalle

Tässä opinnäytetyössä on tarkoituksena selvittää selkeän kielen tarvetta eteisvärinäpotilaan kirjallisessa ohjauksessa sekä tuottaa juurruttamisen menetelmällä varfariinihoitoa saavan potilaan selkeäkielinen hoito-opas. Opinnäytetyö on tehty yhteistyössä perusturvakuntayhtymä Karviaisen terveyskeskuksien henkilökunnan kanssa. Opinnäytetyö on osa Laurea-ammattikorkeakoulun Pumppu-osahanketta. Pumppu-hanke on ylimaakunnallinen vuosina 2011–2014 toteutettava teemahanke, jota rahoittavat Päijät-Hämeen liitto ja Etelä-Suomen maakuntien EU-yksikkö. Laurea-ammattikorkeakoulun Pumppu-osahankkeessa etsitään keinoja asiakkaan terveyden ja hyvinvoinnin edistämiseen sekä hoitamiseen erilaisilla hyvinvointipoluilla. Aineiston tiedonkeruu tehtiin teemahaastattelulla sekä sähköisellä kyselylomakkeella. Vastaukset analysoitiin sisällönanalyysin avulla. Kehittämistoiminnan lopputuotoksena laadittiin selkeäkielinen Marevan®-hoidon miniopas. Marevan®-hoidon miniopas sisältää selkeäkielistä tietoa Marevan®-lääkityksestä, veren hyytymiskyvyn seurannan merkityksestä, lääkkeen annostelusta sekä ruokavalion, alkoholin että muiden lääkkeiden ja luontaistuotteiden vaikutuksista Marevan®-lääkityksessä. Oppaassa on myös kerrottu Marevan®-lääkityksen erityistilanteista, kuten lääkitykseen liittyvistä vaaratekijöistä. Marevan®-hoidon miniopas on otettu työyhteisössä käyttöön toukokuussa 2013. Työyhteisö kerää asiakkailta palautetta minioppaasta puolistrukturoidulla arviointilomakkeella. Palautteiden pohjalta he tulevat jatkossa arvioimaan oppaan käytön ja kehittämisen tarvetta.The development of a clear language patient guide for a patient with warfarin therapy In this thesis the purpose is to find out the need for a clear language written guidance for a patient with atrial fibrillation and produce a clear language patient´s Guide for a patient with warfarin therapy by using dissemination method. The thesis is made in cooperation with the staff of health centers in Karviainen Health District. The thesis is a part of Pumppu subproject in Laurea University for Applied Sciences. The Pumppu project is an interregional theme of the project which to be carried out in 2011- 2014, and is financed by Päijät-Häme Region Association and the EU unit of southern provinces of Finland. A subproject Pumppu in Laurea University for Applied Sciences is searching for ways to promote and care for a customer`s health and welfare by different welfare paths. The material for this thesis was gathered by using a theme interview and an electronic questionnaire. The answers were analyzed by using content analysis. As the final result of development, a clear language mini guide of Marevan® therapy was drawn up. A Marevan® therapy mini guide includes clear language information about Marevan® therapy, the importance of blood clotting ability monitoring, drug delivery and the effects of diet, alcohol, other medicines and natural remedies for medicine in Marevan® therapy. The guide tells also about the specific situations in Marevan® therapy, such as the risk factors of Marevan® therapy. Marevan® therapy mini guide has been introduced at workplace in May 2013. The workplace collects the feedback of the mini guide from the patients with a semi- structured form. On the basis of feedback they will estimate the need of use and development of the guide in the future

Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group

Objectives: The multisystem manifestations of SSc can greatly impact patients’ quality of life. The aim of this study was to identify factors associated with disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (S.D. = 0.66) and 0.92 (S.D. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability

Evidence for a persistent and extensive greening trend in Eurasia inferred from satellite vegetation index data

[1] The northern latitudes have warmed by 0.8°C since the early 1970s, but not all areas have warmed equally. Eurasia shows an overall warming trend, while North America exhibits warming at a lower rate and even a slight cooling trend during the last 50 years in the eastern United States. We analyzed a recently developed satellite normalized difference vegetation index (NDVI) data set (July 1981 to December 1999) to assess vegetation response to these temperature changes. An index of persistence of the NDVI trend was used to generate patches of different levels of persistence. The persistence data were analyzed for patch area, patch perimeter, patch number, patch coherence, largest patch size, patch fragmentation, pixel contiguity, pixel clustering, and conditional probability of pixel adjacency. We address two questions: (1) Is there a difference in the spatial pattern of long-term NDVI increase in comparison to short-term increase? and (2) Are there differences in the spatial patterns of patches between Eurasia and North America? The results indicate a persistent and spatially extensive and connected greening trend in Eurasia, relative to North America. The regions showing short-term greening in Eurasia show a scattered pattern of spatially remote small patches. In North America the long-term greening pattern is spatially fragmented, and a mixture of short- and long-term NDVI increase is found, unlike in Eurasia. Therefore we conclude that the greening trend in Eurasia is more persistent and spatially extensive than in North America, which is qualitatively consistent with near-surface air temperature observations