ABSTRACT
BACKGROUND: Computerized decision support systems have raised a lot of hopes and expectations in the field of order entry. Although there are numerous studies reporting positive impacts, concerns are increasingly high about alert fatigue and effective impacts of these systems. One of the root causes of fatigue alert reported is the low clinical relevance of these alerts. OBJECTIVE: The objective of this systematic review was to assess the reported positive predictive value (PPV), as a proxy to clinical relevance, of decision support systems in computerized provider order entry (CPOE). METHODS: A systematic search of the scientific literature published between February 2009 and March 2015 on CPOE, clinical decision support systems, and the predictive value associated with alert fatigue was conducted using PubMed database. Inclusion criteria were as follows: English language, full text available (free or pay for access), assessed medication, direct or indirect level of predictive value, sensitivity, or specificity. When possible with the information provided, PPV was calculated or evaluated. RESULTS: Additive queries on PubMed retrieved 928 candidate papers. Of these, 376 were eligible based on abstract. Finally, 26 studies qualified for a full-text review, and 17 provided enough information for the study objectives. An additional 4 papers were added from the references of the reviewed papers. The results demonstrate massive variations in PPVs ranging from 8% to 83% according to the object of the decision support, with most results between 20% and 40%. The best results were observed when patients' characteristics, such as comorbidity or laboratory test results, were taken into account. There was also an important variation in sensitivity, ranging from 38% to 91%. CONCLUSIONS: There is increasing reporting of alerts override in CPOE decision support. Several causes are discussed in the literature, the most important one being the clinical relevance of alerts. In this paper, we tried to assess formally the clinical relevance of alerts, using a near-strong proxy, which is the PPV of alerts, or any way to express it such as the rate of true and false positive alerts. In doing this literature review, three inferences were drawn. First, very few papers report direct or enough indirect elements that support the use or the computation of PPV, which is a gold standard for all diagnostic tools in medicine and should be systematically reported for decision support. Second, the PPV varies a lot according to the typology of decision support, so that overall rates are not useful, but must be reported by the type of alert. Finally, in general, the PPVs are below or near 50%, which can be considered as very low.
ABSTRACT
To specifically quantify several metabolites of 5-fluorouracil (5-FU) and two endogenous monophosphate nucleotides, we developed an original method based on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay allowed the determination of: (i) the intracellular production of 5-fluoro-2'-deoxyuridine-5'-monophosphate (5-FdUMP) from 5-FU or 5-fluoro-2'-deoxyuridine (5-FdUrd), (ii) the impact of 5-FdUMP concentration on the intracellular 2'-deoxyuridine-5'-monophosphate (dUMP)/thymidine-5'-monophosphate (TMP) ratio, and (iii) the secretion extent of 5-FdUMP and 5-FU from human cultured cells by ABC transporters. Under our experimental conditions, cells were incubated with 5-FU or 5-FUrd. Then, cellular proteins were precipitated by methanol. This procedure provided high extraction recovery. In addition, to measure 5-FU and 5-FdUMP secretion from cells, we carried out quantification of these molecules in culture medium. Media were either directly injected (5-FU) or underwent a solid phase extraction using Oasis Wax extraction cartridge (5-FdUMP). Separation of analytes was performed on a dC18 Atlantis 3.5microm, (100mmx2.1mm i.d) column with isocratic mode using ammonium formate buffer/methanol/water (5/5/90, v/v) as mobile phase. The run time did not exceed 6.2min. The analytes were ionized in an electrospray interface under negative ion mode. We validated the method over a range of 2.5-150ngmL(-1) according to the compounds. Intra- and inter-assay variability was lower than 10% over seven days. All compounds were stable in cells or in culture medium when samples were stored at -20 degrees C for at least two weeks, and after three freeze-thaw cycles. No matrix effect was observed in both media.
