AB1165 MEDICATION ADHERENCE DATA IN A RANDOMIZED TRIAL: LARGE CHALLENGES TO COME FROM RAW DATA TO A WORKABLE AND RELIABLE DATASET

Background:Medication adherence in the GLORIA trial, among elderly patients with rheumatoid arthritis, is measured with caps that register openings of the medication bottle. At each study visit, one or two medication bottles with cap (kits) are dispensed, each containing 90 capsules. Multiple steps are needed to come to a workable dataset to describe adherence.Objectives:To describe the steps that are needed to come from raw data to a workable dataset to analyze adherence data that are recorded by electronic caps.Methods:The medication bottle contains a cap with the ability to register cap openings. The raw dataset from the caps consist of an excel file with one opening event per row, recorded as date and time. One cap yields approximately 90 rows. First, the kit numbers were matched to the corresponding patient numbers, that are recorded in another excel file. Instances where two kits were dispensed were recorded with two kit numbers in one cell and need to be copied to two cells with one kit number. Second, the VLOOKUP function was used to combine dates and kit numbers. One row now contains all openings from one kit. Then, the number of days between first opening and each next opening date was calculated. A range of 90 days was made to calculate how many times the bottle was opened on each day of the 90-days period. The results were color-coded to visualize instances of zero, one or ≥two openings on a day.Results:The colored calendar matrix (Figure 1) can now be used to categorize adherence patterns.Conclusion:A monitoring cap seems a simple instrument to measure adherence. However, multiple steps and a lot of time are needed to come to a workable dataset for the study of adherence patterns.Acknowledgments:The GLORIA project is funded by the European Union's Horizon 2020 research and innovation programme under the topic "Personalizing Health and Care'', grant agreement No 634886.Disclosure of Interests:Linda Hartman: None declared, Elisa Alessandri: None declared, Reinhard Bos: None declared, Daniela Opris-Belinski Speakers bureau: as declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Griep-Wentink: None declared, Ruth Klaasen: None declared, Cornelia Allaart: None declared, George Bruyn: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Nuno Gomes: None declared, Rui Pinto: None declared, Thomas Klausch: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Maarten Boers: None declare

Lipid-rich Plaques Detected by Near-infrared Spectroscopy Are More Frequently Exposed to High Shear Stress

High wall shear stress (WSS) and near-infrared spectroscopy (NIRS) detected lipid-rich plaque (LRP) are both known to be associated with plaque destabilization and future adverse cardiovascular events. However, knowledge of spatial co-localization of LRP and high WSS is lacking. This study investigated the co-localization of LRP based on NIRS and high WSS. Fifty-three patients presenting acute coronary syndrome underwent NIRS-intravascular-ultrasound (NIRS-IVUS) imaging of a non-culprit coronary artery. WSS was obtained using WSS profiling in 3D-reconstructions of the coronary arteries based on fusion of IVUS-segmented lumen and CT-derived 3D-centerline. Thirty-eight vessels were available for final analysis and divided into 0.5 mm/45° sectors. LRP sectors, as identified by NIRS, were more often colocalized with high WSS than sectors without LRP. Moreover, there was a dose-dependent relationship between lipid content and high WSS exposure. This study is a first step in understanding the evolution of LRPs to vulnerable plaques. [Figure not available: see fulltext.

EMC testing of electricity meters using real-world and artificial current waveforms

In 2015, the energy measurement of some static electricity meters was found to be sensitive to specific conducted electromagnetic disturbances with very fast current changes caused by highly nonlinear loads, leading to meter errors up to several hundred percent. This article describes new results on the electromagnetic compatibility (EMC) of 16 different meters from all over Europe when exposed to real-world disturbance signals. Those test signals were obtained from household appliances and onsite measurements at metered supply points all over Europe. The results show that also the interference signals recorded onsite can cause measurement errors as large as several hundred percent, even for meters that pass the present EMC standards. This unambiguously demonstrates that the present immunity testing standards do not cover the most disturbing conducted interference occurring in present daily-life situations due to the increased use of nonlinear electronics. Furthermore, to enable the adoption of potential new test waveforms in future standards for electricity meter testing, artificial test waveforms were constructed based on real-world waveforms using a piece-wise linear model. These artificial test waveforms were demonstrated to cause meter errors similar to those caused by the original real-life waveforms they are representing, showing that they are suitable candidates for use in improved standardization of electricity meter testing.Postprint (published version

Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders

Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells

Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains 651% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive versus negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs