Erasmus University Medical Center

About: Erasmus University Medical Center is a healthcare organization based out in Rotterdam, Zuid-Holland, Netherlands. It is known for research contribution in the topics: Population & Medicine. The organization has 8162 authors who have published 11395 publications receiving 517117 citations.

Random Effects Models for Longitudinal Data

Abstract: Mixed models have become very popular for the analysis of longitudinal data, partly because they are flexible and widely applicable, partly also because many commercially available software packages offer procedures to fit them. They assume that measurements from a single subject share a set of latent, unobserved, random effects which are used to generate an association structure between the repeated measurements. In this chapter, we give an overview of frequently used mixed models for continuous as well as discrete longitudinal data, with emphasis on model formulation and parameter interpretation. The fact that the latent structures generate associations implies that mixed models are also extremely convenient for the joint analysis of longitudinal data with other outcomes such as dropout time or some time-to-event outcome, or for the analysis of multiple longitudinally measured outcomes. All models will be extensively illustrated with the analysis of real data.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Abstract: To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects) We identified 13 novel T2D-associated loci (P < 5 × 10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology

A consensus approach toward the standardization of back pain definitions for use in prevalence studies

Abstract: A modified Delphi study conducted with 28 experts in back pain research from 12 countries. OBJECTIVE. To identify standardized definitions of low back pain that could be consistently used by investigators in prevalence studies to provide comparable data. SUMMARY OF BACKGROUND DATA. Differences in the definition of back pain prevalence in population studies lead to heterogeneity in study findings, and limitations or impossibilities in comparing or summarizing prevalence figures from different studies. METHODS. Back pain definitions were identified from 51 articles reporting population-based prevalence studies, and dissected into 77 items documenting 7 elements. These items were submitted to a panel of experts for rating and reduction, in 3 rounds (participation: 76%). Preliminary results were presented and discussed during the Amsterdam Forum VIII for Primary Care Research on Low Back Pain, compared with scientific evidence and confirmed and fine-tuned by the panel in a fourth round and the preparation of the current article. RESULTS. Two definitions were agreed on a minimal definition (with 1 question covering site of low back pain, symptoms observed, and time frame of the measure, and a second question on severity of low back pain) and an optimal definition that is made from the minimal definition and add-ons (covering frequency and duration of symptoms, an additional measure of severity, sciatica, and exclusions) that can be adapted to different needs. CONCLUSION. These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.

Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study

Abstract: Summary Background The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy. Methods Patients were recruited to the trial between July 21, 1997, and November 30, 2006, at nine centres in Europe and North America. Patients with localised high-risk STS (≥5 cm, Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep to the fascia) were randomly assigned to receive either neo-adjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone, or combined with regional hyperthermia (EIA plus regional hyperthermia) in addition to local therapy. Local progression-free survival (LPFS) was the primary endpoint. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00003052. Findings 341 patients were enrolled, with 169 randomly assigned to EIA plus regional hyperthermia and 172 to EIA alone. All patients were included in the analysis of the primary endpoint, and 332 patients who received at least one cycle of chemotherapy were included in the safety analysis. After a median follow-up of 34 months (IQR 20–67), 132 patients had local progression (56 EIA plus regional hyperthermia vs 76 EIA). Patients were more likely to experience local progression or death in the EIA-alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0·58, 95% CI 0·41–0·83; p=0·003), with an absolute difference in LPFS at 2 years of 15% (95% CI 6–26; 76% EIA plus regional hyperthermia vs 61% EIA). For disease-free survival the relative hazard was 0·70 (95% CI 0·54–0·92, p=0·011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28·8%, compared with 12·7% in the group who received chemotherapy alone (p=0·002). In a pre-specified per-protocol analysis of patients who completed EIA plus regional hyperthermia induction therapy compared with those who completed EIA alone, overall survival was better in the combined therapy group (HR 0·66, 95% CI 0·45–0·98, p=0·038). Leucopenia (grade 3 or 4) was more frequent in the EIA plus regional hyperthermia group compared with the EIA-alone group (128 of 165 vs 106 of 167, p=0·005). Hyperthermia-related adverse events were pain, bolus pressure, and skin burn, which were mild to moderate in 66 (40·5%), 43 (26·4%), and 29 patients (17·8%), and severe in seven (4·3%), eight (4·9%), and one patient (0·6%), respectively. Two deaths were attributable to treatment in the combined treatment group, and one death was attributable to treatment in the EIA-alone group. Interpretation To our knowledge, this is the first randomised phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Adding regional hyperthermia to chemotherapy is a new effective treatment strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location. Funding Deutsche Krebshilfe, Helmholtz Association (HGF), European Organisation of Research and Treatment of Cancer (EORTC), European Society for Hyperthermic Oncology (ESHO), and US National Institute of Health (NIH).