| 1. |
- Areskoug Sandberg, Elin, et al.
(author)
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Saliva Cortisol in Girls With Functional Abdominal Pain Disorders : A Randomized Controlled Dance and Yoga Intervention.
- 2022
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In: Frontiers in Pediatrics. - : Frontiers Media S.A.. - 2296-2360. ; 10
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Functional abdominal pain disorders (FAPDs) are common among girls and has been associated with stress. Cortisol is one of the major stress hormones. Dance and yoga have been shown to reduce abdominal pain among girls with FAPDs.AIM: To investigate the effect of an 8-month intervention with dance and yoga on cortisol levels in saliva among girls with FAPDs.METHODS: A total of 121 girls aged 9-13 years with irritable bowel syndrome (IBS) or functional abdominal pain were included in the study. Participants were randomized into an intervention group and a control group. The intervention group attended a combined dance and yoga session twice a week for 8 months. Saliva samples were collected during 1 day, in the morning and evening, at baseline, and at 4 and 8 months. Subjective pain and stress were assessed as well.RESULTS: No significant effects on saliva cortisol levels between groups were observed after completion of the intervention at 8 months. However, evening cortisol and evening/morning quotient were significantly reduced at 4 months in the intervention group compared to the control group (p = 0.01, p = 0.004). There was no association between cortisol quota and pain or stress.CONCLUSION: Improvements in cortisol levels were seen in the intervention group at 4 months but did not persist until the end of the study. This indicates that dance and yoga could have a stress-reducing effect during the ongoing intervention.
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| 2. |
- de Ridder, Lissy, et al.
(author)
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Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease : A Multinational Study from the Porto Pediatric IBD Group
- 2014
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In: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 20:2, s. 291-300
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Journal article (peer-reviewed)abstract
- Background: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. Results: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Conclusions: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.
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| 3. |
- Degraeuwe, Pieter L J, et al.
(author)
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Faecal calprotectin in suspected paediatric inflammatory bowel disease.
- 2015
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 60:3, s. 339-346
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data.METHODS: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator.RESULTS: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 μg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94).CONCLUSIONS: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.
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| 4. |
- Eberhardson, Michael, et al.
(author)
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Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
- 2022
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In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
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Journal article (peer-reviewed)abstract
- Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
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| 5. |
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| 6. |
- Fagerberg, Ulrika Lorentzon
(author)
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Fecal calprotectin in children with special reference to inflammatory bowel disease
- 2007
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Doctoral thesis (other academic/artistic)abstract
- This thesis aims to study the clinical usefulness of fecal calprotectin as a noninvasive marker of colonic inflammation in children with suspected or confirmed chronic inflammatory bowel disease (IBD). Calprotectin, a calcium-binding protein predominantly expressed in neutrophils, is stable in feces for several days, and can be measured by an enzyme-linked immunosorbent assay. Gastrointestinal symptoms as abdominal pain, diarrhea, bloody stools, and weight loss are common in children presenting with IBD. However, the symptoms can be vague, or even similar to the symptoms of other more common gastrointestinal disorders and functional complaints. Early recognition of IBD is important to prevent adverse effects such as delayed onset of puberty, impaired growth, and unnecessary suffering. The routine investigations include blood tests, fecal cultures, endoscopy, and radiological examinations. Endoscopy with histological examinations of biopsy specimens is the gold standard for diagnosis. It is also used for objective estimation of disease activity and to monitor the efficacy of treatment. However, endoscopy is unsuitable for frequent use as it is an invasive and costly procedure requiring careful bowel preparation and, in children, general anesthesia. Study I establishes reference values for fecal calprotectin by analyzing fecal samples from 117 healthy children and adolescents. The conclusion was that the upper reference value for fecal calprotectin concentration is <50 mug/g in boys and girls aged 4 through 17 years. Study II evaluates the feasibility of fecal calprotectin to detect colorectal inflammation in children. Fecal samples were collected from 36 children with gastrointestinal symptoms suggestive of IBD before undergoing colonoscopy. Elevated fecal calprotectin concentrations strongly predicted the presence of IBD or other colorectal inflammation, and the test had a sensitivity of 95% and specificity of 93%. Thus, fecal calprotectin can be used as a diagnostic tool to facilitate selection of children who should undergo diagnostic colonoscopy. Study III aimed to evaluate fecal calprotectin as a quantitative marker of inflammatory activity in pediatric IBD. Thirty-nine children with IBD delivered fecal samples and underwent colonoscopies. The results demonstrated that fecal calprotectin is a valid surrogate marker for quantitative estimation of colonic inflammation in pediatric IBD. Normalized fecal calprotectin concentration seems to indicate complete, histological mucosal healing. Study IV compared plasma calprotectin, high sensitivity C-reactive protein and serum amyloid A with fecal calprotectin and routine blood tests as markers of histological inflammation in 32 children with IBD. Fecal calprotectin measurement was found to be a more reliable test for estimation of histological inflammatory activity in the colon. In conclusion, the present thesis demonstrates that fecal calprotectin is a simple and noninvasive method that can be used as a sensitive diagnostic tool to detect colorectal inflammation and IBD in children with gastrointestinal symptoms. Further, the fecal calprotectin method was shown to be useful as a quantitative, surrogate marker of colonic inflammatory activity. The simplicity of obtaining and analyzing fecal calprotectin will facilitate the care of children with gastrointestinal symptoms as well as the monitoring of inflammatory activity in pediatric IBD.
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| 7. |
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| 8. |
- Hindorf, Ulf, et al.
(author)
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Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease
- 2006
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In: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 24:2, s. 331-342
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Journal article (peer-reviewed)abstract
- Background: Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease. Aims: To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event. Methods: Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database. Results: The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%, P < 0.001) and in low to intermediate (≤9.0 U/mL red blood cell) than normal thiopurine methyltransferase activity (P = 0.02). Myelotoxicity developed later than other types of adverse event. An increased frequency of adverse event was observed in patients with tioguanine (thioguanine) nucleotide above 400 or methylated thioinosine monophosphate above 11 450 pmol/ 8 × 108 red blood cell. A shift to mercaptopurine was successful in 48% of azathioprine-intolerant patients and in all cases of azathioprine-induced myalgia or arthralgia. Conclusions: A pre-treatment determination of thiopurine methyltransferase status might be appropriate as patients with low to intermediate thiopurine methyltransferase activity are more prone to develop an adverse event, determination of metabolite levels can be useful in the case of an adverse event. Mercaptopurine therapy should be considered in azathioprine-intolerant patients. © 2006 The Authors.
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| 9. |
- Hjortswang, Henrik, et al.
(author)
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Infliximab in clinical routine : Experience with Crohn's disease and biomarkers of inflammation over 5 years
- 2009
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In: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 21:10, s. 1168-1176
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Journal article (peer-reviewed)abstract
- Introduction: Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. Aim: To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). Methods: During 1999–2008, CD patients were monitored for disease activity by Harvey–Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. Results: A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey–Bradshaw index decreased with infusions during the first year of treatment (P<0.0001), whereas hemoglobin (P<0.01) and albumin (P<0.001) increased, C-reactive protein (P<0.01) decreased, platelets (P<0.001) increased, and leukocytes (P<0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P<0.0001), and nitrite (P<0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Conclusion: Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.
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| 10. |
- Häussler, Ragna S., et al.
(author)
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Systematic Development of Sandwich Immunoassays for the Plasma Secretome
- 2019
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861.
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Journal article (peer-reviewed)abstract
- The plasma proteome offers a clinically useful window into human health. Recent advances from highly multiplexed assays now call for appropriate pipelines to validate individual candidates. Here, a workflow is developed to build dual binder sandwich immunoassays (SIA) and for proteins predicted to be secreted into plasma. Utilizing suspension bead arrays, ≈1800 unique antibody pairs are first screened against 209 proteins with recombinant proteins as well as EDTA plasma. Employing 624 unique antibodies, dilution-dependent curves in plasma and concentration-dependent curves of full-length proteins for 102 (49%) of the targets are obtained. For 22 protein assays, the longitudinal, interindividual, and technical performance is determined in a set of plasma samples collected from 18 healthy subjects every third month over 1 year. Finally, 14 of these assays are compared with with SIAs composed of other binders, proximity extension assays, and affinity-free targeted mass spectrometry. The workflow provides a multiplexed approach to screen for SIA pairs that suggests using at least three antibodies per target. This design is applicable for a wider range of targets of the plasma proteome, and the assays can be applied for discovery but also to validate emerging candidates derived from other platforms.
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