Pilot study on developing a decision support tool for guiding re-administration of chemotherapeutic agent after a serious adverse drug reaction

<p>Abstract</p> <p>Background</p> <p>Currently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR) incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process.</p> <p>Methods</p> <p>The inclusion criteria for patients in this study are: (1) had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2) suffered from serious ADRs, and (3) were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients.</p> <p>Results</p> <p>Eight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level) were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model.</p> <p>Conclusion</p> <p>Due to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate.</p

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.

Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of 'common genes' (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD

Foreign Trade Statistical Bulletin Imports December 2009

The data presented in this publication comprises import by HS type of good, SITC good classification, commodity (HS), country of origin, port of import, five main good classification 3 digit SITC, some commodity and main country of origin. It also presents Import of Connected Area by 2 digit good classification, SITC good classification, country of origin, province and port of import

IPA network showing the network with the second largest number of up-regulated focus genes in the hypertension plus hypercholesterolemia group, compared with sham operated controls.

<p>IPA network showing the network with the second largest number of up-regulated focus genes in the hypertension plus hypercholesterolemia group, compared with sham operated controls.</p

Venn diagram of DEGs in the MCA of hypertension only rabbits; hypercholesterolemia plus sham operated rabbits; and hypertension plus hypercholesterolemia rabbits; all vs. sham operated control rabbits.

<p>A: total number of genes, B: up-regulated genes C: down-regulated genes (One gene which is common between the Hypertension only- and Hypertension plus hypercholesterolemia group was both up- and down-regulated, and omitted).</p

Mean arterial pressure and serum cholesterol levels in rabbits.

<p>(A) Mean arterial pressure in hypertension only rabbits. (B) Serum cholesterol levels in hypertension only rabbits. (C) Mean arterial pressure in hypercholesterolemia plus sham- and hypertension plus hypercholesterolemia rabbits. (D) Serum cholesterol levels in hypercholesterolemia plus sham- and hypertension plus hypercholesterolemia rabbits. H: Hypertension only. HC: Hypercholesterolesterolemia plus sham operation. HTHC: Hypertension plus hypercholesterolemia. MAP: mean arterial pressure. Data are expressed as mean ± SEM. *<i>p</i><0.05, **<i>p</i><0.01 vs. control (Student’s t-test in A,B; repeated measure ANOVA followed by Tukey test in C,D).</p

IPA network showing the network with the largest number of up-regulated focus genes in the hypercholesterolemia plus sham group, compared with sham operated controls.

<p>IPA network showing the network with the largest number of up-regulated focus genes in the hypercholesterolemia plus sham group, compared with sham operated controls.</p

Up-regulated genes in the MCA that are common between ‘hypertension only’ and ‘hypercholesterolemia plus sham’ rabbits (both vs. sham controls) with greater than 4-fold change (see Fig. 2).

<p>Up-regulated genes in the MCA that are common between ‘hypertension only’ and ‘hypercholesterolemia plus sham’ rabbits (both vs. sham controls) with greater than 4-fold change (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068335#pone-0068335-g002" target="_blank">Fig. 2</a>).</p