| 1. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 2. |
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| 3. |
- Beard, David J., et al.
(författare)
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Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
- 2020
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Ingår i: The Lancet. - 0140-6736. ; 395:10226, s. 828-838
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Forskningsöversikt (refereegranskat)abstract
- Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.
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| 4. |
- Beard, David J., et al.
(författare)
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Placebo comparator group selection and use in surgical trials : The aspire project including expert workshop
- 2021
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Ingår i: Health Technology Assessment. - 1366-5278. ; 25:53
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space.
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| 5. |
- Elding Larsson, Helena, et al.
(författare)
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Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes : A randomized clinical trial
- 2018
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 19:3, s. 410-419
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Treatments have failed to delay or stop the autoimmune process, preceding onset of type 1 diabetes. We investigated if autoantigen-specific treatment with alum-formulated glutamate decarboxylase (GAD-Alum) was safe and affected progression to type 1 diabetes in children with islet autoimmunity.METHODS: In an investigator-initiated, double-blind, placebo-controlled clinical trial, non-diabetic children aged 4 to 17.9 years with autoantibodies to glutamate decarboxylase (GADA) and at least one of insulinoma-associated protein 2, insulin or zinc-transporter 8, were randomized, stratified by 2 or ≥3 islet autoantibodies, to 2 injections of 20 μg GAD-Alum or placebo, 30 days apart. Main outcome was safety, investigated by adverse events, hematology, chemistry, thyroid and celiac autoimmunity and titers of islet autoantibodies, and efficacy, investigated by cumulative incidence of diabetes onset over 5-year follow-up. Secondary variables: change in first-phase insulin release (FPIR) after intravenous glucose tolerance tests, fasting, 120 minutes and Area under the curve (AUC) C-peptide and p-glucose after oral glucose tolerance tests and HbA1c.RESULTS: Fifty children (median age: 5.2) were assigned 1:1 to GAD-Alum or placebo, all receiving full treatment and included in the analyses. GAD-Alum did not affect any safety parameter, while GADA titers increased (P = .001). Time to clinical diagnosis was not affected by treatment (hazard ratio, HR = 0.77, P = .574) in the full population or in the separate stratum groups. Treatment did not affect any of the secondary variables.CONCLUSIONS: GAD-Alum as a subcutaneous prime and boost injection was safe in prediabetic young children but did not affect progression to type 1 diabetes. The safety of GAD-Alum should prove useful in future prevention studies.
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| 6. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 7. |
- Kordonouri, Olga, et al.
(författare)
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Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals : the TRIGR cohort
- 2022
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 65, s. 2098-2107
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. Methods A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. Results Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). Conclusions/interpretation We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.
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| 8. |
- Lehtonen, Eveliina, et al.
(författare)
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Use of vitamin D supplements during infancy in an international feeding trial.
- 2014
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Ingår i: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 17:4, s. 810-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.DESIGN: Longitudinal study.SETTING: Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.SUBJECTS: Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.RESULTS: Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80% of the infants), with somewhat lower rates observed in Southern Europe (> 60%). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g., 71% v. 44% at 6 months of age). Less than 2% of infants in the U.S.A. and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.CONCLUSIONS: Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the U.S.A. and Australia very few were given supplementation.
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| 9. |
- Ludvigsson, Johnny, et al.
(författare)
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Increasing plasma glucose before the development of type 1 diabetes-the TRIGR study
- 2021
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Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 22:7, s. 974-981
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The beta-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp < 0.001) and the development of diabetes (p < 0.002 resp < 0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes.
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