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Mirza A.H.,Copenhagen University | Berthelsen C.H.B.,Copenhagen University | Berthelsen C.H.B.,Novo Nordisk AS | Seemann S.E.,Copenhagen University | And 6 more authors.
Genome Medicine | Year: 2015

Background: Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn's disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. Methods: In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in 96 colon pinch biopsies (inflamed and non-inflamed) extracted from multiple colonic locations from 45 patients (CD = 13, UC = 20, controls = 12) using an expression microarray platform. Results: In our study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In cases of inflamed CD and UC, we identified 438 and 745 differentially expressed lncRNAs, respectively, while in cases of the non-inflamed CD and UC, we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (P-value <0.001, Pearson's Chi-squared test) for 96 differentially expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility loci. Furthermore, we found strong positive expression correlations for the intersecting and cis-neighboring differentially expressed IBD loci-associated lncRNA-protein-coding gene pairs. The functional annotation analysis of differentially expressed genes revealed their involvement in the immune response, pro-inflammatory cytokine activity and MHC protein complex. Conclusions: The lncRNA expression profiling in both inflamed and non-inflamed CD and UC successfully stratified IBD patients from the healthy controls. Taken together, the identified lncRNA transcriptional signature along with clinically relevant parameters suggest their potential as biomarkers in IBD. © 2015 Mirza et al.


Rossi A.,Sg Moscati Hospital | Chiodini P.,The Second University of Naples | Sun J.-M.,Sungkyunkwan University | O'Brien M.E.R.,Royal Marsden Hospital | And 11 more authors.
The Lancet Oncology | Year: 2014

Background: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare the efficacy of six versus fewer planned cycles of platinum-based chemotherapy. Methods: All randomised trials comparing six versus fewer planned cycles of first-line platinum-based chemotherapy for patients with advanced non-small-cell lung cancer were eligible for inclusion in this systematic review and meta-analysis. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients with an objective response, and toxicity. Statistical analyses were by intention-to-treat, stratified by trial. Overall survival and progression-free survival were compared by log-rank test. The proportion of patients with an objective response was compared with a Mantel-Haenszel test. Prespecified analyses explored effect variations by trial and patient characteristics. Findings: Five eligible trials were identified; individual patient data could be collected from four of these trials, which included 1139 patients-568 of whom were assigned to six cycles, and 571 to three cycles (two trials) or four cycles (two trials). Patients received cisplatin (two trials) or carboplatin (two trials). No evidence indicated a benefit of six cycles of chemotherapy on overall survival (median 9·54 months [95% CI 8·98-10·69] in patients assigned to six cycles vs 8·68 months [8·03-9·54] in those assigned to fewer cycles; hazard ratio [HR] 0·94 [95% CI 0·83-1·07], p=0·33) with slight heterogeneity between trials (p=0·076; I2=56%). We recorded no evidence of a treatment interaction with histology, sex, performance status, or age. Median progression-free survival was 6·09 months (95% CI 5·82-6·87) in patients assigned to six cycles and 5·33 months (4·90-5·62) in those assigned to fewer cycles (HR 0·79, 95% CI 0·68-0·90; p=0·0007), and 173 (41·3%) of 419 patients assigned to six cycles and 152 (36·5%) of 416 patients assigned to three or four cycles had an objective response (p=0·16), without heterogeneity between the four trials. Anaemia at grade 3 or higher was slightly more frequent with a longer duration of treatment: 12 (2·9%) of 416 patients assigned to three-to-four cycles and 32 (7·8%) of 411 patients assigned to six cycles had severe anaemia. Interpretation: Six cycles of first-line platinum-based chemotherapy did not improve overall survival compared with three or four courses in patients with advanced non-small-cell lung cancer. Our findings suggest that fewer than six planned cycles of chemotherapy is a valid treatment option for these patients. Funding: None. © 2014 Elsevier Ltd.


Lokkegaard E.,North Zealand Hospital | Nielsen A.K.,North Zealand Hospital
Danish Medical Journal | Year: 2014

INTRODUCTION: Use of hormonal contraceptives for birth control is commonplace in the Western World. In Europe, there is considerable variety in the frequency of use of hormonal contraceptives and in the age at which these contraceptives are initiated. The purpose of the present study was to describe the use of hormonal contraceptives among the Danish adolescent female population, focusing on age, period and cohort effects and including types of hormonal contraceptives. MATERIAL AND METHODS: All women aged 14-50 years during the 1995-2012 period were identified through the Central Person Register. Furthermore, the National Registry of Medicinal Products Statistics provided information on redeemed prescriptions for hormonal contraceptives characterised by Anatomical-Therapeutic-Chemical (ATC) classification codes. RESULTS: At the age of 17 years, more than 50% of the Danish adolescent population had redeemed a prescription for hormonal contraceptives. At the age of 20 years, 85% had ever used hormonal contraceptives. This amounts to a significant decrease in age at which hormonal contraceptives were initiated in the younger birth cohorts compared to the older cohorts. Additionally, adolescent girls have more pauses and shifts between types of hormonal contraceptives. Since 2010 there has been a shift toward use of second generation oral contraceptives away from third and fourth generation contraceptives. CONCLUSION: Adolescent girls tend to initiate their use of oral contraceptives at a younger age than the older cohorts do. Furthermore, they have more pauses and shift between products more frequently than older cohorts. The type of oral contraceptive used has shifted since 2010 towards older products with second generation progestins. © 2014, Danish Medical Association. All rights reserved.


PubMed | Hvidovre Hospital, University of Southern Denmark, North Zealand Hospital, Herlev Hospital and Herning Hospital
Type: | Journal: European journal of obstetrics, gynecology, and reproductive biology | Year: 2016

The risk of obstetric anal sphincter injury (OASIS) is increased in vacuum-assisted delivery. However, it remains unclear whether episiotomy may protect against OASIS in this type of delivery. The objective of this study was to assess whether mediolateral or lateral episiotomy affects the risk of OASIS in vacuum-assisted delivery among primiparous women. Data were found searching The PubMed, Cochrane library and Embase databases electronically. Studies investigating the risk of OASIS in vacuum-assisted delivery with and without the use of mediolateral or lateral episiotomy were considered for inclusion. Of the 452 studies found, 15 observational studies were included in this meta-analysis. All authors assessed risk of bias of the included studies using the Scottish Intercollegiate Guideline Network (SIGN) quality score. According to this meta-analysis, mediolateral or lateral episiotomy significantly reduced the risk of OASIS in vacuum-assisted deliveries in primiparous women (OR 0.53 (95% CI 0.37-0.77)). Numbers needed to treat (NNT) was 18.3 (95% CI 17.7-18.9). The protective effect of episiotomy seemed most pronounced when performed in more than 75% of vacuum-assisted deliveries (OR 0.37 (95% CI 0.15-0.92)). In conclusion, this meta-analysis showed that mediolateral or lateral episiotomy was protective against OASIS and may be considered in vacuum-assisted delivery in primiparous women. Randomized controlled trials to further investigate this finding are warranted.


PubMed | University of Aalborg, University of Southern Denmark, North Zealand Hospital and Copenhagen University
Type: Journal Article | Journal: European journal of preventive cardiology | Year: 2016

Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients with diabetes compared to the background population in Denmark.Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02-0.02), 0.99 (0.98-1.01), 8.89 (8.81-8.98) and 20.0 (19.9-20.2) in the background population and 0.13 (0.09-0.20), 2.10 (2.00-2.20), 8.41 (8.10-8.74) and 20.1 (19.4-20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52-3.60), 1.52 (1.47-1.56), 1.20 (1.18-1.23) and 0.99 (0.97-1.01) in the four age groups, respectively.Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients.Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high relative risk. Increased focus on detecting atrial fibrillation in young diabetes patients might prove beneficial, and both anticoagulation treatment and anti-arrhythmic treatment strategies should be considered as soon as possible.


PubMed | North Zealand Hospital and Copenhagen University
Type: Journal Article | Journal: Clinical physiology and functional imaging | Year: 2016

The major salivary glands, submandibular, parotid and sublingual glands play an important role in preserving the oral cavity and dental health. Patients with problems of the major salivary glands may present with symptoms such as dry mouth, dysphagia and obstruction of duct, inflammation, severe dental caries or swelling. Imaging plays an important role in visualization of morphology and function, to establish a diagnosis, for treatment, and for surgical planning. There are several options for diagnostic imaging: plain radiography, sialography, ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), salivary gland scintigraphy and (18)F-FDG positron emission tomography (PET). We present an overview of the modalities in relation to common salivary gland disease.


PubMed | Private Practice, North Zealand Hospital, a Psychiatric Center Nordsjaelland and Copenhagen University
Type: Journal Article | Journal: Nordic journal of psychiatry | Year: 2016

Background Delirium is a frequent psychiatric complication to cancer, but rarely recognized by oncologists. Aims 1. To estimate the prevalence of delirium among inpatients admitted at an oncological cancer ward 2. To investigate whether simple clinical factors predict delirium 3. To examine the value of cognitive testing in the assessment of delirium. Methods On five different days, we interviewed and assessed patients admitted to a Danish cancer ward. The World Health Organization International Classification of Diseases Version 10, WHO ICD-10 Diagnostic System and the Confusion Assessment Method (CAM) were used for diagnostic categorization. Clinical information was gathered from medical records and all patients were tested with Mini Cognitive Test, The Clock Drawing Test, and the Digit Span Test. Results 81 cancer patients were assessed and 33% were diagnosed with delirium. All delirious participants were CAM positive. Poor performance on the cognitive tests was associated with delirium. Medical records describing CNS metastases, benzodiazepine or morphine treatment were associated with delirium. Conclusions Delirium is prevalent among cancer inpatients. The Mini Cognitive Test, The Clock Drawing Test, and the Digit Span Test can be used as screening tools for delirium among inpatients with cancer, but even in synergy, they lack specificity. Combining cognitive testing and attention to nurses records might improve detection, yet further studies are needed to create a more detailed patient profile for the detection of delirium.


PubMed | Bristol Royal Hospital for Children, Copenhagen University, New York University, Erasmus MC Sophia Childrens Hospital and 6 more.
Type: Journal Article | Journal: Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery | Year: 2016

Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up.Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions.A new, proposed definition of post-operative pediatric CMS was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed.The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS.


PubMed | University of Aalborg, North Zealand Hospital and Copenhagen University
Type: | Journal: BMC nursing | Year: 2016

There appears to be divergence between nurses and patients perceptions of dyspnoea onset and on how help should be given. This may affect how nurses understand and assess their patients anxiety and the severity of dyspnoea, potentially diminishing their chances of relieving patients dyspnoea. The aim of this study was to explore nurse-patient interaction in situations where patients with chronic obstructive pulmonary disease are experiencing acute or worsened dyspnoea in a hospital setting.An ethnographic study using participant observation of two nurses interactions with six patients, followed by qualitative in-depth interviews with the nurses. Data were analysed in three steps. First, they were coded for identification of preliminary themes. Second, data were regrouped into preliminary themes for focused analysis which led to formulation of themes and subthemes. Third, hermeneutical principles were used as all data were interpreted from the viewpoint of each theme.Three themes were identified: Manoeuvring along the edge; Dyspnoea within the pattern; and Dyspnoea outside the pattern. They were encompassed by the main finding: Manoeuvring along the edge of breathlessness. The nurses attempted to navigate between implicit and explicit care approaches and to create a sphere for relieving or avoiding further worsening of dyspnoea. Depending on the identified pattern for a particular dyspnoeic episode, nurses attributed different significance to the dyspnoea.Interacting in dyspnoeic situations places nurses in a dilemma: an implicit approach risk, deriving from exclusion of patients and performing hesitantly; or an explicit negotiation risk, where patients are exhausted and removed from focusing and breathing. The dilemma weakens nurses opportunities to relieve or avoid a worsening of the dyspnoea. Likewise, the divergence between nurses and patients assessment of dyspnoea as within or outside the pattern appears to jeopardize the efficiency of care. Our findings contribute to a deeper understanding of the challenges of respiratory nursing care in general, and the challenges of relieving in-patients dyspnoea in particular.


PubMed | Roskilde Hospital, North Zealand Hospital and Herlev and Gentofte Hospital
Type: Journal Article | Journal: PloS one | Year: 2016

Low levels of serum 25-hydroxy vitamin D are associated with increased arterial stiffness and hypertension. Supplementation with vitamin D precursors has been proposed as a treatment option for these conditions. We examined the effect of oral cholecalciferol on arterial stiffness and blood pressure in healthy normotensive adults.40 healthy adults were randomised in this double-blinded study to either oral cholecalciferol 3000 IU/day or matching placebo and were followed for 16 weeks to examine any effects on pulse wave velocity (PWV), augmentation index (AIx), peripheral and central blood pressure and 24-hour ambulatory blood pressure.22 subjects in the cholecalciferol arm and 18 subjects in the placebo arm completed the 16 weeks of follow-up. There was no difference in changes in PWV, AIx corrected for heart rate or central or peripheral blood pressure between the two groups. There was no correlation between serum 25-hydroxy vitamin D and any of these parameters.Oral cholecalciferol 3000 IU/day does not affect arterial stiffness or blood pressure after 16 weeks of treatment in healthy normotensive adults.ClinicalTrials.gov NCT00952562.

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