| 1. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 2. |
- Wintzell, Viktor, et al.
(författare)
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Association between azathioprine use and risk of acute pancreatitis in pediatric inflammatory bowel disease : A nationwide Swedish cohort study
- 2018
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 27:Suppl. 2, s. 196-196
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Studies have shown an association between use of azathioprine and acute pancreatitis in adult inflammatory bowel disease. However, whether there is an association among pediatric patients isnot known.Objectives: To investigate if there is an association between use of azathioprine and the risk of acute pancreatitis in pediatric inflammatory bowel disease (pIBD) patients.Methods: We conducted a nationwide Swedish cohort study based on health care register data, 2006‐2014. From a cohort of all pediatric patients (<18 years) with IBD (n = 4631), we included 1477 episodes of new azathioprine use and 1477 episodes of no use in propensity score‐matched (1:1 ratio) analyses. The propensity score included patient characteristics, comorbidities, previous treatment, indicators of disease severity and health care utilization. Incident cases of acute pancreatitis occurring in the primary risk period of 90 days following treatment initiation were identified through outpatient and inpatient hospital records. A sensitivity analysis was restricted to inpatient cases alone. A secondary risk period of 91‐365 days following treatment initiation was also assessed. Cox proportional hazards models were used to estimate hazard ratios (HRs).Results: Among azathioprine‐exposed, mean age was 14.3 (SD 3.2) years, 56.5% were male, and 56.1% had Crohn's disease and 43.9% had ulcerative colitis or IBD‐unclassified. During the first 90 days following azathioprine initiation, 23 patients (1.6%) experienced acute pancreatitis compared with 5 patients (0.3%) in the no use group; corresponding incidence rates were 65 and 16 per 1000 person‐years. The risk was significantly higher in patients with azathioprine use, HR = 4.21 (95% CI 1.60‐11.08). The HR was similar when only considering acute pancreatitis events in inpatient care (4.82 [1.65‐14.03]) and there was no increased risk during the period 91‐365 days following treatment initiation (0.36 [0.03‐4.01]).Conclusions: Use of azathioprine was associated with an increased risk of acute pancreatitis in pIBD during the first 90 days of use but not later. The finding suggests that the risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategy in pIBD. Additional analyses also including nationwide Danish data are ongoing and will be presented at the conference.
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| 3. |
- Wintzell, Viktor, et al.
(författare)
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Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease : a Swedish-Danish nationwide cohort study
- 2019
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Ingår i: Lancet Child and Adolescent Health. - : Elsevier. - 2352-4642 .- 2352-4650. ; 3:3, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known. We aimed to investigate whether use of azathioprine is associated with the risk of acute pancreatitis in children with inflammatory bowel disease.Methods: We did a nationwide register-based cohort study in Sweden (2006-16) and Denmark (2000-16). All paediatric patients (<18 years of age) with inflammatory bowel disease during the study period were identified through hospital records. Episodes of incident azathioprine use and no use of any thiopurine were matched (1:1) using propensity scores, controlling for sociodemographic characteristics, comorbidities, previous treatment, indicators of disease severity, and health care use. Incident acute pancreatitis (physician-assigned diagnosis with ICD-10 code K85) occurring in the 90 days following treatment initiation were identified through outpatient and inpatient hospital records.Findings: We identified 3574 azathioprine episodes and 18 700 no-use episodes, which resulted in 3374 pairs after propensity score matching; baseline characteristics in the matched cohort were well balanced. Among the matched azathioprine episodes, mean age was 14.3 years (SD 3.1), 1854 (54.9%) were male, 1923 (57.0%) had Crohn's disease, and 1451 (43.0%) had ulcerative colitis or unclassified inflammatory bowel disease. Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49.1 events per 1000 person-years) compared with six events in the no-use group (8.4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5.82 [95% CI 2.47-13.72]; absolute difference 1.0 [95% CI 0.3-2.6] events per 100 patients) during the 90-day risk period.Interpretation: Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies.
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| 4. |
- Wintzell, Viktor, et al.
(författare)
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Data Mining for Adverse Events of Tumor Necrosis Factor-Alpha Inhibitors in Pediatric Patients : Tree-Based Scan Statistic Analyses of Danish Nationwide Health Data
- 2020
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Ingår i: Clinical drug investigation. - : Springer. - 1173-2563 .- 1179-1918. ; 40:12, s. 1147-1154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Tumor necrosis factor-alpha (TNF-α) inhibitors are efficacious and considered generally safe in adults. However, pediatric-specific safety evidence is scarce. The aim of this study was to screen for signals of previously unknown adverse events of TNF-α inhibitors in pediatric patients.METHODS: We conducted a data-mining study based on routinely collected, nationwide Danish healthcare data for 2004-2016. Using tree-based scan statistics to identify events with unexpectedly high incidence during TNF-α inhibitor use among patients with inflammatory bowel disease or juvenile idiopathic arthritis, two analyses were performed: comparison with episodes of no use and with other time periods from the same patient. Based on incident physician-assigned diagnosis codes from outpatient and inpatient visits in specialist care, we screened thousands of potential adverse events while adjusting for multiple testing.RESULTS: We identified 1310 episodes of new TNF-α inhibitor use that met the eligibility criteria. Two signals of adverse events of TNF-α inhibitors, as compared with no use, were detected. First, there were excess events of dermatologic complications (ICD-10: L00-L99, 87 vs. 44 events, risk difference [RD] 3.3%), which have been described previously in adults and children. Second, there were excess events of psychiatric diagnosis adjustment disorders (ICD-10: F432, 33 vs. 7 events, RD 2.0%), which was likely associated with the underlying disease and its severity, rather than with the treatment. The self-controlled analysis generated no signal.CONCLUSIONS: No signals of previously unknown adverse events of TNF-α inhibitors in pediatric patients were detected. The study showed that real-world data and newly developed methods for adverse events data mining can play a particularly important role in pediatrics where pre-approval drug safety data are scarce.
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| 5. |
- Wintzell, Viktor, et al.
(författare)
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Use of tumour necrosis factor-α inhibitors and the risk of serious infection in paediatric inflammatory bowel disease in Denmark : a nationwide cohort study
- 2019
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Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 4:11, s. 845-853
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies have shown an association between use of tumour necrosis factor-α (TNFα) inhibitors and increased risk of serious infection in adult inflammatory bowel disease (IBD). However, data on this topic for paediatric patients are scarce and inconclusive. The aim of this study was to investigate whether there is an association between the use of TNFα inhibitors and the risk of serious infection in children with IBD.METHODS: In this nationwide Danish cohort study, we searched health registers (from Jan 1, 2007, to Dec 31, 2016) to identify episodes of children and adolescents (<18 years) with at least two recorded IBD diagnoses in specialist care. We categorised follow-up time in mutually exclusive episodes of incident TNFα inhibitor use or no TNFα inhibitor use from specialist care records. We used Cox proportional hazards models to estimate hazard ratios (HRs), adjusting using propensity score weighting for demographic characteristics, comorbidities, treatment history, health-care use, and indicators of disease severity. The primary outcome, incident serious infection, was defined as infection requiring a stay in hospital and was identified through hospital records.FINDINGS: Among 2817 paediatric patients with IBD, we identified 618 episodes of incident TNFα inhibitor use and 2925 episodes of no TNFα inhibitor use. In the cohort of exposed and not exposed episodes that was propensity-score weighted, 53·9% were of male sex, the mean age was 15·1 (SD 1·7) years, 69·9% had Crohn's disease, and 30·1% had ulcerative colitis or IBD-unclassified; median follow-up was 1·4 years (IQR 0·4-3·0). The weighted incidence of serious infection was 54·6 events per 1000 patient-years for the TNFα inhibitor episodes and 61·9 events per 1000 patient-years for the no-use episodes. The weighted HR of serious infection associated with TNFα inhibitor use was 0·81 (95% CI 0·54-1·21).INTERPRETATION: There was no significant association between use of TNFα inhibitors and the risk of serious infection in children with IBD, and, based on the upper bound of the confidence interval, a relatively small risk increase seems unlikely, contrary to previous findings in adults. Observational data such as these can support paediatric clinical practice.
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