1
revisión
Publicado 2021
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This study was funded by the National Institute for Health Research (NIHR) School for Primary Care Research, project number 444. JCB was sponsored by FONDECYT- CONCYTEC (grant contract number 231-2015- FONDECYT). TPM, TMP and JRC were supported by the Medical Research Council (grant numbers MC_UU_12023/ 21 and MC_UU_12023/29). The study sponsors only had a funding role in this research. Thus, the researchers worked with total independence from their sponsors.
2
artículo
Publicado 2020
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Background: In the interrupted time series (ITS) approach, it is common to average the outcome of interest at each time point and then perform a segmented regression (SR) analysis. In this study, we illustrate that such ‘aggregate-level’ analysis is biased when data are missing at random (MAR) and provide alternative analysis methods. Methods: Using electronic health records from the UK, we evaluated weight change over time induced by the initiation of antipsychotic treatment. We contrasted estimates from aggregate-level SR analysis against estimates from mixed models with and without multiple imputation of missing covariates, using individual-level data. Then, we conducted a simulation study for insight about the different results in a controlled environment. Results: Aggregate-level SR analysis suggested a substantial weight gain after initiation of treatment (average short-term we...
3
artículo
Publicado 2020
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Background: Antipsychotics are often prescribed for long-term periods, however, most evidence of their impact on body weight comes from short-term clinical trials. Particularly, impact associated with dosage has been barely studied. Aims: The aim of this study was to describe the short- and long-term change in body weight of people initiated on high or low doses of the three most commonly prescribed second-generation antipsychotics. Methods: Retrospective cohorts of individuals with a diagnosed psychotic disorder observed from 2005 to 2015 in the UK primary care. The exposure was the first prescription of olanzapine, quetiapine or risperidone. The main outcome was change in body weight four years before and four years after initiation of antipsychotic treatment, stratified on sex and ‘low’ or ‘high’ dose. Results: In total, 22,306 women and 16,559 men were observed. Olanzapine tr...
4
artículo
Publicado 2022
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Patients with DICER1 predisposition syndrome have an increased risk to develop pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, and several other rare tumor entities. In this study, we identified 22 primary intracranial sarcomas, including 18 in pediatric patients, with a distinct methylation signature detected by array-based DNA-methylation profiling. In addition, two uterine rhabdomyosarcomas sharing identical features were identified. Gene panel sequencing of the 22 intracranial sarcomas revealed the almost unifying feature of DICER1 hotspot mutations (21/22; 95%) and a high frequency of co-occurring TP53 mutations (12/22; 55%). In addition, 17/22 (77%) sarcomas exhibited alterations in the mitogen-activated protein kinase pathway, most frequently affecting the mutational hotspots of KRAS (8/22; 36%) and mutations or deletions of NF1 (7/22; 32%), followed by muta...
