Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: Results from 8 years' surveillance in the Danish nationwide DANBIO registry
Glintborg B.,Gentofte University Hospital |
Ostergaard M.,Copenhagen University |
Krogh N.S.,Zitelab Aps |
Dreyer L.,Rigshospitalet |
And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2010
Objectives: To use prospectively registered data from the Danish nationwide rheumatological database (DANBIO) to describe disease activity, clinical response, treatment duration and predictors of drug survival (ie, number of days individual patients maintained treatment) and clinical response among patients with ankylosing spondylitis (AS) receiving their first treatment series with a tumour necrosis factor α (TNFα) inhibitor. Methods: 842 TNFα inhibitor naive patients with AS were identified in DANBIO. Clinical response, drug survival and predictors thereof were investigated. 'Clinical response' was defined as a 50% or 20 mm reduction in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) within 6 months compared with baseline. Achievement of a BASDAI <40 mm within 6 months was used as a second response parameter. Results: 603 patients (72%) were men, disease duration 5 (1-13) years (median (IQR), age 41 (32-50) years. 445 (53%) received infliximab, 247 (29%) adalimumab and 150 (18%) etanercept. Parameters at baseline/1-year follow-up were: C-reactive protein (CRP): 14 (7-27)/5 (2-10) mg/l, BASDAI 59 (44-72)/21 (8-39) mm, Bath Ankylosing Spondylitis Functional Index (BASFI) 50 (34-67)/24 (9-45) mm, Bath Ankylosing Spondylitis Metrology Index 40 (20-50)/20 (10-40) mm. Within 6 months, 407/644 patients (63%) achieved a clinical response. Median drug survival was 4.3 years. One- and 2-year survival rates were 74% and 63%, respectively. Baseline characteristics associated with longer drug survival were male gender, CRP >14 mg/l and low visual analogue scale fatigue (Cox regression analysis). Age, TNFα inhibitor and methotrexate use were insignificant. CRP >14 mg/l, lower BASFI and younger age at baseline was associated with clinical response and achievement of a BASDAI <40 mm (logistic regression analysis). Conclusion: TNFα inhibitors provide a rapid and sustained decrease of disease activity among patients with AS in clinical practice. Factors associated with continued treatment, clinical response and achievement of a BASDAI <40 mm were identified.
Dessau R.B.,Slagelse Hospital
Journal of Medical Microbiology | Year: 2013
Two assays (Liaison, Diasorin; IDEIA, Oxoid) for detection of Borrelia-specific antibodies were compared. A case-control design using patients with neuroborreliosis (n = 48), laboratory defined by a positive Borrelia-specific antibody index in the spinal fluid, was available and was intended to represent the serological response of disseminated early Lyme borreliosis in general. Serum samples were obtained from 216 Danish blood donors as controls. By comparing sensitivity and specificity using pre-specified cut-off values, significant differences were found. However, using receiver operating characteristic (ROC) curves to optimize and standardize test interpretation, it was shown that testing with both IDEIA IgG and IgM was comparable to testing with Liaison IgG alone by comparing the area under the curve of the diagnostically relevant 25 % partial ROC curve (P = 0.1). When using the Liaison OspC/VlsE IgM assay, the specificity was decreased without a gain in sensitivity. This study proposes standardizing of reporting by using a control population as the reference and choosing decision thresholds guided by the risk of false-positive results at 2 and 8 %. The sensitivities for IDEIA (IgG and IgM combined) were 85 and 95 % and for the Liaison (VlsE IgG) method were 67 and 96 %, respectively. Methods for test evaluation, test interpretation and statistical testing are presented and discussed. In conclusion, Liaison VlsE IgG alone and IDEIA IgG/IgM combined showed a high and comparable discriminatory ability to distinguish serum samples from patients with neuroborreliosis from blood donor controls. However, cut-off values should be adjusted for a proper comparison. © 2013 SGM.
Perdawood S.K.,Slagelse Hospital |
Lund T.,Slagelse Hospital
Techniques in Coloproctology | Year: 2015
Background: Extralevator abdominoperineal excision (ELAPE) probably improves the oncological quality of low rectal cancer surgery, as compared to standard abdominoperineal excision (SAPE), possibly due to lower rates of accidental perioperative bowel perforations and lower rates of circumferential resection margin (CRM) positivity. The procedure may however, increase post-operative morbidity. The aim of this paper was to compare outcomes of SAPE and ELAPE for carcinoma of the lower rectum.Methods: This is a retrospective study of patients operated on at a single colorectal unit, in a provincial hospital in Denmark. Consecutive patients undergoing abdominoperineal excision (APE) between 2006 and 2012 were included. During this period, a gradual paradigm shift occurred towards adopting ELAPE, although both procedures were performed without a clear selection strategy. We reviewed medical records, including the pathological and radiological data. Patients were divided into two groups, SAPE and ELAPE. Main endpoints were rates of positive CRM, intraoperative bowel perforations, local recurrence rate, length of hospital stay, operative time, and perineal wound-related complications.Results: One hundred and seven patients were included (median age 68 years, range 42–88 years; men = 72). The SAPE group included 39 patients and the ELAPE group 68 patients. Intraoperative bowel perforation was significantly lower in the ELAPE group (20.5 % SAPE vs 7.4 % ELAPE, p = 0.045). The rate of positive CRM was not significantly different (2.6 % SAPE vs 7.4 % ELAPE, p = 0.413). The local recurrence rate was not statistically significant (17.9 % SAPE vs 13.2 % ELAPE, p = 0.513). In the ELAPE group, operative time and hospital stay were significantly longer than the SAPE group (p = 0.001 and p = 0.021, respectively).Conclusions: We found low rates of positive CRM after APE compared with the literature. ELAPE did not reduce these rates, and although the local recurrence rate was lower, this did not reach statistical significance. ELAPE has significantly reduced the rate of intraoperative bowel perforation and can optimize low rectal cancer surgery in selected patients. We found no significant differences between the two procedures regarding wound-related complications. A tailored approach and a larger trial with longer follow-up are needed to evaluate long-term results. © 2014, Springer-Verlag Italia Srl.
Elias D.,University of Southern Denmark |
Vever H.,University of Southern Denmark |
Laenkholm A.-V.,Slagelse Hospital |
Gjerstorff M.F.,University of Southern Denmark |
And 3 more authors.
Oncogene | Year: 2015
To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analyses and identified 366 genes with altered expression in four unique tamoxifen-resistant (TamR) cell lines vs the parental tamoxifen-sensitive MCF-7/S0.5 cell line. Most of these genes were functionally linked to cell proliferation, death and control of gene expression, and include FYN, PRKCA, ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN-specific small interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell lines while exerting no significant effect on MCF-7/S0.5 cells. Moreover, overexpression of FYN in parental tamoxifen-sensitive MCF-7/S0.5 cells resulted in reduced sensitivity to tamoxifen treatment, whereas knockdown of FYN in the FYN-overexpressing MCF-7/S0.5 cells restored sensitivity to tamoxifen, demonstrating growth- and survival-promoting function of FYN in MCF-7 cells. FYN knockdown in TamR cells led to reduced phosphorylation of 14-3-3 and Cdc25A, suggesting that FYN, by activation of important cell cycle-associated proteins, may overcome the anti-proliferative effects of tamoxifen. Evaluation of the subcellular localization of FYN in primary breast tumors from two cohorts of endocrine-treated ER+ breast cancer patients, one with advanced disease (N=47) and the other with early disease (N=76), showed that in the former, plasma membrane-associated FYN expression strongly correlated with longer progression-free survival (P<0.0002). Similarly, in early breast cancer patients, membrane-associated expression of FYN in the primary breast tumor was significantly associated with increased metastasis-free (P<0.04) and overall (P<0.004) survival independent of tumor size, grade or lymph node status. Our results indicate that FYN has an important role in tamoxifen resistance, and its subcellular localization in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer. © 2015 Macmillan Publishers Limited. All rights reserved.
Perdawood S.K.,Slagelse Hospital |
Al Khefagie G.A.A.,Slagelse Hospital
Colorectal Disease | Year: 2016
Aim: Laparoscopic total mesorectal excision (LaTME) has improved short-term outcomes of rectal cancer surgery with comparable oncological results to open approach. LaTME can be difficult in the lowermost part of the rectum, leading potentially to higher rates of complications, conversion to open surgery and probably suboptimal oncological quality. Transanal TME (TaTME) can potentially solve these problems. The aim of this study was to compare the short-term results after TaTME with those after LaTME. Method: A prospectively collected database of consecutive patients who underwent TaTME was maintained. Results were compared with those who underwent LaTME in the preceding period. Patients who underwent low anterior resection or intersphincteric abdominoperineal excision were included. Primary end-points were radical resection and specimen quality. Secondary end-points were complications, rates of conversion, operating time and hospital stay. Results: In total, 50 patients were included (TaTME = 25, LaTME = 25). The groups were comparative in demographic data and tumour characteristics. Circumferential resection margin was positive in one patient in the TaTME group vs four patients in the LaTME group (P = 0.349). All patients in the TaTME group had either complete or nearly complete specimen quality, while four patients in the LaTME group had incomplete specimen quality (P = 0.113). Less blood loss, shorter operating time and shorter hospital stay were found in the TaTME group (P values 0.016, 0.002 and 0.020 respectively). Intra-operative complications were comparable (P = 0.286). Conclusion: The TaTME procedure had comparable pathological results and acceptable short-term postoperative outcomes compared to LaTME. © 2016 The Association of Coloproctology of Great Britain and Ireland.
Carstensen M.,Slagelse Hospital |
Moller A.M.,Herlev University Hospital
British Journal of Anaesthesia | Year: 2010
In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient-controlled analgesia (PCA) for postoperative pain in order to clarify this controversy. Our primary aim was to compare the effectiveness and safety of postoperative administered ketamine in addition to opioid for i.v. PCA compared with i.v. PCA with opioid alone. Studies were identified from the Cochrane Library 2003, MEDLINE (1966-2009), and EMBASE (1980-2009) and by hand-searching reference lists from review articles and trials. Eleven studies were identified with a total of 887 patients. Quality and validity assessment was performed on all trials included using the Oxford Quality Scale with an average quality score of 4.5. Pain was assessed using visual analogue scales or verbal rating scales. Six studies showed significant improved postoperative analgesia with the addition of ketamine to opioids. Five studies showed no significant clinical improvement. For thoracic surgery, the addition of ketamine to opioid for i.v. PCA was superior to i.v. PCA opioid alone. The combination allows a significant reduction in pain score, cumulative morphine consumption, and postoperative desaturation. The benefit of adding ketamine to morphine in i.v. PCA for orthopaedic or abdominal surgery remains unclear. Owing to huge heterogeneity of studies and small sample sizes, larger double-blinded randomized studies showing greater degree of homogeneity are required to confirm these findings. © The Author . Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
Nielsen H.L.,Aarhus University Hospital |
Engberg J.,Slagelse Hospital |
Ejlertsen T.,Aarhus University Hospital |
Bucker R.,Charité - Medical University of Berlin |
Nielsen H.,Aarhus University Hospital
Clinical Microbiology and Infection | Year: 2012
There are only sparse data on the short-term and medium-term clinical impacts of Campylobacter concisus infection. A clinical study was performed during a 2-year period to determine the clinical manifestations in C. concisus-positive adult patients. A case patient was defined as an adult patient (≥18 years) with a C. concisus-positive stool sample during the study period. Clinical data were obtained with use of a questionnaire supplemented with the patients' medical records, if any. The short-term and medium-term clinical manifestations in these patients were compared with those of patients with Campylobacter jejuni/Campylobacter coli infection. One hundred and seventy-four C. concisus patients and 196 C. jejuni/C. coli patients participated in the study. Patients with pre-existing inflammatory bowel disease or microscopic colitis or enteric co-infection were excluded from review of the clinical manifestations. Comparison of the short-term clinical manifestations in 139 C. concisus patients with those in 187 C. jejuni/C. coli patients showed a significantly lower prevalence of fever, chills, mucus and blood in stools, and weight loss. However, 80% of C. concisus patients, but only 32% of C. jejuni/C. coli patients, had diarrhoea for >2 weeks. After a 6-month follow-up period, 12% of C. concisus patients were diagnosed with microscopic colitis, whereas no C. jejuni/C. coli patients were diagnosed with non-infective colitis. Irritable bowel symptoms were common in both groups at follow-up. C. concisus infection seems to cause a milder course of acute gastroenteritis than C. jejuni/C. coli infection, but is associated with more prolonged diarrhoea. © 2012 European Society of Clinical Microbiology and Infectious Diseases.
Wennervaldt K.,Slagelse Hospital |
Melchiors J.,Slagelse Hospital
Danish Medical Journal | Year: 2012
Introduction: Endoscopic examination and treatment of disorders in the oesophagus has been a part of the otolaryngological specialty since the introduction of the rigid endoscope. Today, both flexible and rigid oesophagoscopy (RO) is used to that end. The aim of this study was to evaluate the safety of the RO. Material and methods: We conducted a retrospective cohort study of all ROs performed at a head & neck department in a Danish hospital in the 2003-2011-period. Perforation of the oesophageal wall was the primary endpoint. Secondary endpoints included: dental injury, mortality and, in case of a foreign body; location and successful removal. Results: A total of 483 ROs were performed. Four patients (0.8%) suffered perforation; three during removal of a foreign body in the lower part of the oesophagus and one as part of investigation for cancer. 46.2% of the procedures were performed to remove a foreign body and 32.7% as investigation for cancer. The majority of the foreign bodies were located in the superior part of the oesophagus and the objects were successfully removed in all but one case. Conclusion: Our results are well within the range of previously published material. We recommend that the risk of serious complications is taken into consideration when choosing this modality. Furthermore, we believe that this risk increases in the distal part of the oesophagus and recommend that the use of the RO in this area is reserved as a last resort option.
Thorlund J.B.,University of Southern Denmark |
Hare K.B.,University of Southern Denmark |
Hare K.B.,Slagelse Hospital |
Lohmander L.S.,University of Southern Denmark |
Lohmander L.S.,Lund University
Acta Orthopaedica | Year: 2014
Background - Arthroscopic meniscal surgery is the most common orthopedic procedure, and the incidence has increased in Denmark over the last 10 years. Concomitantly, several randomized controlled trials have shown no benefit of arthroscopic procedures including arthroscopic partial meniscectomy in middle-aged and older individuals suffering from knee pain with or without knee osteoarthritis. We examined the annual incidence of meniscal procedures together with age, sex, and diagnosis for patients who underwent meniscal procedures in the period 2000-2011 in Denmark. Methods - Data on age, sex, diagnosis, and surgical procedures were extracted from the Danish National Patient Register for the years 2000-2011, for all records containing meniscal surgery as a primary or secondary procedure. Results - The overall annual incidence of meniscal procedures per 100,000 persons in Denmark doubled from 164 in 2000 to 312 in 2011 (i.e. 8,750 procedures to 17,368 procedures). A 2-fold increase was found for patients aged between 35 and 55, and a 3-fold increase was found for those older than 55. Middle-aged and older patients accounted for 75% of all 151,228 meniscal procedures carried out between 2000 and 2011. Interpretation - The incidence of meniscal procedures performed in Denmark doubled from 2000 to 2011, with the largest increase in middle-aged and older patients. This increase contrasts with the mounting evidence showing no added benefit of arthroscopic partial meniscectomy over non-surgical treatments. Our observations illustrate the long delay in the dissemination, acceptance, and implementation of research evidence into the practice of arthroscopic surgery. © Nordic Orthopaedic Federation.
Nielsen H.L.,Aarhus University Hospital |
Ejlertsen T.,Aarhus University Hospital |
Engberg J.,Slagelse Hospital |
Nielsen H.,Aarhus University Hospital
Clinical Microbiology and Infection | Year: 2013
The incidence of non-thermophilic Campylobacter species was assessed in an unselected population-based study in a mixed urban and rural community in North Jutland, Denmark. In a 2-year study period, 11314 faecal samples from 8302 patients with gastroenteritis were cultured with supplement of the filter method. We recovered a high incidence of Campylobacter concisus (annual incidence 35/100000 inhabitants), almost as high as the common Campylobacter jejuni/coli. In contrast, there was a very low incidence of other non-thermophilic Campylobacter species, such as Campylobacter upsaliensis. Campylobacter concisus was, unlike C. jejuni/coli, found more frequently among small children (<1year) and the elderly (≥65years). Around 10% of the patients with C. consisus had co-infections dominated by Clostridium difficile and Salmonella enterica, whereas co-infections occurred in about 5% of C. jejuni/coli patients. We observed a seasonal variation in C. jejuni/coli with a peak incidence in late summer months and autumn, whereas there was an almost constant monthly prevalence of C. concisus. Among patients participating in a questionnaire sub-study, there was a higher degree of close contacts with animals, especially dogs, as well as a higher travel exposure among C. jejuni/coli patients compared with C. concisus patients. We did not culture any C. concisus in stool samples from a small cohort of healthy individuals. Future studies have to focus on the clinical follow-up and the long-term risk of inflammatory bowel diseases in C. concisus-positive patients. We conclude that there is a high incidence of C. concisus in Denmark. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.