2 research outputs found
The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype
Because of genetic heterogeneity, the identification of breast
cancer-susceptibility genes has proven to be exceedingly difficult. Here,
we define a new subset of families with breast cancer characterized by the
presence of colorectal cancer cases. The 1100delC variant of the cell
cycle checkpoint kinase CHEK2 gene was present in 18% of 55 families with
hereditary breast and colorectal cancer (HBCC) as compared with 4% of 380
families with non-HBCC (P<.001), thus providing genetic evidence for the
HBCC phenotype. The CHEK2 1100delC mutation was, however, not the major
predisposing factor for the HBCC phenotype but appeared to act in synergy
with another, as-yet-unknown susceptibility gene(s). The unequivocal
definition of the HBCC phenotype opens new avenues to search for thi
Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study
Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients