Esbjerg, Denmark
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Haga H.-J.,University of Aalborg | Schmedes A.,Lillebaelt Hospital | Naderi Y.,Sydvestjysk Sygehus | Moreno A.M.,National Hospital | Peen E.,University of Aalborg
Clinical Rheumatology | Year: 2013

This study aims to measure the serum level of 25-hydroxyvitamin D 3 (25-OH-D3) in 302 patients with rheumatoid arthritis (RA), studying the association to disease activity. Three hundred two RA patients underwent clinical examination and serological analysis. 25-Hydroxyvitamin D3 was determined by high-performance liquid chromatography-tandem mass spectrometry. Vitamin D3 deficiency defined as serum levels of 25-hydroxyvitamin D3 below 50 nmol/l was detected in 101 RA patients (33.4 %). There was no significant correlation between the serum level of 25-hydroxyvitamin D3 and Disease Activity Score 28 (DAS28) (3w) score. In a subpopulation of RA patients with very low serum level of 25-OH-D3 (≤15 nmol/l) (n = 15), there were significant differences compared to patients with normal 25-OH-D3 (n = 200): higher percentage of patients with positive rheumatoid factor (100.0 versus 77.5 %; p = 0.05), higher CRP (28.7 versus 14.8 mg/l; p = 0.001), higher number of patients treated with at least three disease-modifying antirheumatic drugs (DMARDs) (40.0 versus 14.5 %; p = 0.02), higher number of patients with high disease activity DAS28 score of ≥5.1 (20.0 versus 4.5 %; p = 0.01), lower age (54.5 versus 64.0 years; p = 0.003) and shorter disease duration (5.1 versus 10.3 years; p = 0.06). Deficiency of 25-hydroxyvitamin D3 was detected in 33.4 % of the RA patients. A subpopulation of patients with severe deficiency of vitamin D3 serum level of ≤15 nmol/l was characterised by all being positive for rheumatoid factor, high percentage of patients with very high disease activity and high percentage of patients treated with at least three DMARDs. © 2013 Clinical Rheumatology.


Haga H.-J.,University of Aalborg | Naderi Y.,Sydvestjysk Sygehus | Moreno A.M.,National Hospital | Peen E.,University of Aalborg
International Journal of Rheumatic Diseases | Year: 2012

Aim: To examine the prevalence of sicca symptoms and secondary Sjögren's syndrome (sSS) in rheumatoid arthritis (RA) patients, and the impact of sSS on disease activity and treatment profile in RA patients. Methods: Three hundred and seven RA patients responding positive to at least one of the questions in a questionnaire about sicca symptoms, were examined by Schirmer I test for tear production, and unstimulated whole saliva collection (USWC). Secondary Sjögren's syndrome was defined by at least one subjective sicca symptom, in addition to a positive Schirmer I test and positive USWC. Results: Among the 307 RA patients, 86 (28%) responded positive to at least one question about sicca symptoms, and 11 patients were positive for both Schirmer I and USWC tests, giving a minimum prevalence of sSS at 3.6%. There were no differences in RA patients with and without sSS regarding age, sex, disease duration, disease activity score (DAS-28) and seropositivity for anti-cyclic citrullinated protein. RA patients with sSS had a tendency for higher numbers of tender and swollen joints and pain. None of the RA patients treated with tumor necrosis factor (TNF) inhibitors had sSS, compared to 22% of the rest of the RA population studied. The treatment of the RA patients with and without sSS was not different. Conclusion: Among the 307 RA patients, 28% had at least one sicca symptom. The estimated minimum of prevalence of sSS in 307 RA patients was 3.6%. Secondary Sjögren's syndrome was not found in RA patients treated with biologics such as TNF blockers. © 2012 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.


Arendrup M.C.,Statens Serum Institute | Dzajic E.,Sydvestjysk Sygehus | Jensen R.H.,Statens Serum Institute | Johansen H.K.,Copenhagen University | And 10 more authors.
Clinical Microbiology and Infection | Year: 2013

Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes. © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Oxlund C.S.,University of Southern Denmark | Henriksen J.E.,University of Southern Denmark | Tarnow L.,Steno Diabetes Center | Schousboe K.,Sygehus Lillebaelt | And 2 more authors.
Journal of Hypertension | Year: 2013

Background: The increased risk of cardiovascular morbidity and mortality associated with arterial hypertension is particularly pronounced in patients with type 2 diabetes mellitus. Blood pressure control is, therefore, decisively important but often not sufficiently achieved. Objective: The primary objective of this study was to evaluate the antihypertensive effect of low dose spironolactone added to triple therapy for resistant hypertension in patients with type 2 diabetes measured by ambulatory monitoring. Secondary objectives were to evaluate the effects on glycaemic control and urinary albumin excretion as well as adverse effects. Methods: In a multicentre, double-blind, randomized, placebo-controlled study 119 patients with blood pressure at or above 130/80mmHg despite triple antihypertensive therapy were included. One tablet of 25mg spironolactone or placebo was added to previous treatment and increased to two if blood pressure below 130/80mmHg was not achieved after 4 weeks. Blood pressure was measured by ambulatory monitoring at baseline and after 16 weeks. Results: The study was completed by 112 patients, 57 randomized to spironolactone and 55 to placebo. Average daytime placebo-corrected blood pressure was reduced by 8.9 (4.7-13.2)/3.7 (1.5-5.8)mmHg. Also office blood pressure, night-time, 24-h and pulse pressures were reduced significantly. Urinary albumin/creatinine ratio was significantly reduced in the spironolactone group. Glycaemic control remained unchanged. Hyperkalemia was the most frequent adverse event leading to dose reduction in three cases and discontinuation in one, whereas gynaecomastia was not reported. Conclusion: Low dose spironolactone exerts significant BP and urinary albumin creatinine ratio lowering effects in high-risk patients with resistant hypertension and type 2 diabetes mellitus. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Brabrand M.,Sydvestjysk Sygehus | Folkestad L.,Sydvestjysk Sygehus | Clausen N.G.,Sygehus Lillebaelt | Knudsen T.,Sydvestjysk Sygehus | Hallas J.,University of Southern Denmark
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Year: 2010

Background: Patients referred to a medical admission unit (MAU) represent a broad spectrum of disease severity. In the interest of allocating resources to those who might potentially benefit most from clinical interventions, several scoring systems have been proposed as a triaging tool.Even though most scoring systems are not meant to be used on an individual level, they can support the more inexperienced doctors and nurses in assessing the risk of deterioration of their patients.We therefore performed a systematic review on the level of evidence of literature on scoring systems developed or validated in the MAU. We hypothesized that existing scoring systems would have a low level of evidence and only few systems would have been externally validated.Methods: We conducted a systematic search using Medline, EMBASE and the Cochrane Library, according to the PRISMA guidelines, on scoring systems developed to assess medical patients at admission.The primary endpoints were in-hospital mortality or transfer to the intensive care unit. Studies derived for only a single or few diagnoses were excluded.The ability to identify patients at risk (discriminatory power) and agreement between observed and predicted outcome (calibration) along with the method of derivation and validation (application on a new cohort) were extracted.Results: We identified 1,655 articles. Thirty were selected for further review and 10 were included in this review.Eight systems used vital signs as variables and two relied mostly on blood tests.Nine systems were derived using regression analysis and eight included patients admitted to a MAU. Six systems used in-hospital mortality as their primary endpoint.Discriminatory power was specified for eight of the scoring systems and was acceptable or better in five of these. The calibration was only specified for four scoring systems. In none of the studies impact analysis or inter-observer reliability were analyzed.None of the systems reached the highest level of evidence.Conclusions: None of the 10 scoring systems presented in this article are perfect and all have their weaknesses. More research is needed before the use of scoring systems can be fully implemented to the risk assessment of acutely admitted medical patients. © 2010 Brabrand et al; licensee BioMed Central Ltd.


Brabrand M.,Sydvestjysk Sygehus | Folkestad L.,Sydvestjysk Sygehus | Hallas P.,Sydvestjysk Sygehus
Ugeskrift for Laeger | Year: 2010

Introduction: Many emergency departments use validated triage tools. It is currently undocumented if such a practice is common in Danish medical admission units (MAU). The current study was conducted in order to clarify this. Method: Questionnaire survey with data collected from the intern on call at the medical departments of all Danish hospitals listed on sundhed.dk. Results: We received 87 answers from 60 individual MAUs covered by a total of 83 interns on call. The MAUs had a median of eight beds and 14 admissions a day. An intern was on call 24 hours a day at 95% of the MAUs. At 87% of the MAUs, a doctor was contacted by the admitting physician, while the contact was the responsibility of a nurse in 13% of MAUs. None of the contacted MAUs used a validated triage tool and 95% answered that they triaged on the basis of individual clinical assessment of patients. However, 22% answered that selected groups of patients were routinely assessed by a senior physician. Conclusion: None of the Danish MAUs uses a validated triage tool to prioritize acutely admitted medical patients.


Arendrup M.C.,Statens Serum Institute | Mavridou E.,Radboud University Nijmegen | Mortensen K.L.,Statens Serum Institute | Snelders E.,Radboud University Nijmegen | And 4 more authors.
PLoS ONE | Year: 2010

Four sequential Aspergillus fumigatus isolates from a patient with chronic granulomatous disease (CGD) eventually failing azole-echinocandin combination therapy were investigated. The first two isolates (1 and 2) were susceptible to antifungal azoles, but increased itraconazole, voriconazole and posaconazole MICs were found for the last two isolates (3 and 4). Microsatellite typing showed that the 4 isolates were isogenic, suggesting that resistance had been acquired during azole treatment of the patient. An immunocompromised mouse model confirmed that the in vitro resistance corresponded with treatment failure. Mice challenged with the resistant isolate 4 failed to respond to posaconazole therapy, while those infected by susceptible isolate 2 responded. Posaconazole-anidulafungin combination therapy was effective in mice challenged with isolate 4. No mutations were found in the Cyp51A gene of the four isolates. However, expression experiments of the Cyp51A showed that the expression was increased in the resistant isolates, compared to the azolesusceptible isolates. The microscopic morphology of the four isolates was similar, but a clear alteration in radial growth and a significantly reduced growth rate of the resistant isolates on solid and in broth medium was observed compared to isolates 1 and 2 and to unrelated wild-type controls. In the mouse model the virulence of isolates 3 and 4 was reduced compared to the susceptible ones and to wild-type controls. For the first time, the acquisition of azole resistance despite azole-echinocandin combination therapy is described in a CGD patient and the resistance demonstrated to be directly associated with significant change of0020virulence. © 2010 Arendrup et al.


Mrgan M.,Sydvestjysk Sygehus | Nielsen S.,Sydvestjysk Sygehus | Brixen K.,University of Southern Denmark
Acta Clinica Croatica | Year: 2014

Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign autosomal dominant disease characterized by hypercalcemia, normal to increased parathyroid hormone level, and a relatively low renal calcium excretion. Inactivation of the calcium-sensing receptor in heterozygous patients results in FHH, while in homozygous patients as well as in compound heterozygous or dominant negative heterozygous patients, it may result in neonatal severe hyperparathyroidism (NSHPT). Parathyroid surgery is not indicated in FHH and does not lower plasma calcium unless total parathyroidectomy is performed, in which case hypocalcemia ensues. There is currently no definitive medical treatment available, although pamidronate can be used to stabilize these patients before parathyroidectomy. Some NSHPT patients are asymptomatic subsequently in their lives. In this paper, clinical characteristics of this relatively rare disorder are presented.


Molin R.,Holbaek Sygehus | Hallas P.,Rigshospitalet | Brabrand M.,Sydvestjysk Sygehus | Schmidt T.A.,Holbaek Sygehus
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Year: 2010

Background: Intraosseous infusion (IOI) is recommended when intravenous access cannot be readily established in both pediatric and adult resuscitation. We evaluated the current use of IOI in Danish emergency departments (EDs).Methods: An online questionnaire was e-mailed to the Heads of Department of the twenty EDs currently established in Denmark. The questionnaire focused on the use of IOI in the EDs and included questions on frequency of use, training, equipment and attitudes towards IOI.Results: We received a total of 19 responses (response rate of 95%). Of the responding 19 Danish EDs 74% (n = 14) reported having intraosseous devices available. The median number of IOI procedures performed in these departments over the preceding 12 months was 5.0 (range: 0-45). In 47% (n = 9) of the departments, prior training sessions in the use of intraosseous devices had not been provided, and 42% (n = 8) did not have local guidelines on IOI. The indication for IOI use was often not clearly defined and only 11% (n = 2) consistently used IOI on relevant indication. This is surprising as 95% (n = 18) of responders were aware that IOI can be utilized in both pediatric and adult resuscitation.Conclusions: The study shows considerable variations in IOI usage in Danish EDs despite the fact that IOI devices were available in the majority of EDs. In addition, in many EDs there were no local guidelines on IOI and no training in the procedure. We recommend more extensive training of medical staff in IOI techniques in Danish EDs. © 2010 Molin et al; licensee BioMed Central Ltd.


Henriksen D.P.,University of Southern Denmark | Brabrand M.,Sydvestjysk Sygehus | Lassen A.T.,University of Southern Denmark
PLoS ONE | Year: 2014

Objective: Patients that initially appear stable on arrival to the hospital often have less intensive monitoring of their vital signs, possibly leading to excess mortality. The aim was to describe risk factors for deterioration in vital signs and the related prognosis among patients with normal vital signs at arrival to a medical emergency department (MED). Design and setting: Single-centre, retrospective cohort study of all patients admitted to the MED from September 2010- August 2011. Subjects: Patients were included when their vital signs (systolic blood pressure, pulse rate, respiratory rate, Glasgow Coma Scale, oxygen saturation and temperature) were within the normal range at arrival. Deterioration was defined as a deviation from the defined normal range 2-24 hours after arrival. Results: 4292 of the 6257 (68.6%) admitted to the MED had a full set of vital signs at first presentation, 1440/4292 (33.6%) had all normal vital signs and were included in study, 44.0% were male, median age 64 years (5th/95th percentile: 21-90 years) and 446/1440 (31.0%) deteriorated within 24 hours. Independent risk factors for deterioration included age 65-84 years odds ratio (OR): 1.79 (95% confidence interval [CI]: 1.27-2.52), 85+ years OR 1.67 (95% CI: 1.10-2.55), Do-not-attempt-to-resuscitate order OR 3.76 (95% CI: 1.37-10.31) and admission from the open general ED OR 1.35 (95% CI: 1.07-1.71). Thirty-day mortality was 7.9% (95% CI: 5.5-10.7%) among deteriorating patients and 1.9% (95% CI: 1.2-3.0%) among the non-deteriorating, hazard ratio 4.11 (95% CI: 2.38-7.10). Conclusions: Among acutely admitted medical patients who arrive with normal vital signs, 31.0% showed signs of deterioration within 24 hours. Risk factors included old age, Do-not-attempt-to-resuscitate order, admission from the open general ED. Thirty-day mortality among patients with deterioration was four times higher than among non-deteriorating patients. Further research is needed to determine whether intensified monitoring of vital signs can help to prevent deterioration or mortality among medical emergency patients. © 2014 Henriksen et al.

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