Clinical decision support tools: analysis of online drug information databases

BACKGROUND: Online drug information databases are used to assist in enhancing clinical decision support. However, the choice of which online database to consult, purchase or subscribe to is likely made based on subjective elements such as history of use, familiarity, or availability during professional training. The purpose of this study was to evaluate clinical decision support tools for drug information by systematically comparing the most commonly used online drug information databases. METHODS: Five commercially available and two freely available online drug information databases were evaluated according to scope (presence or absence of answer), completeness (the comprehensiveness of the answers), and ease of use. Additionally, a composite score integrating all three criteria was utilized. Fifteen weighted categories comprised of 158 questions were used to conduct the analysis. Descriptive statistics and Chi-square were used to summarize the evaluation components and make comparisons between databases. Scheffe's multiple comparison procedure was used to determine statistically different scope and completeness scores. The composite score was subjected to sensitivity analysis to investigate the effect of the choice of percentages for scope and completeness. RESULTS: The rankings for the databases from highest to lowest, based on composite scores were Clinical Pharmacology, Micromedex, Lexi-Comp Online, Facts & Comparisons 4.0, Epocrates Online Premium, RxList.com, and Epocrates Online Free. Differences in scope produced three statistical groupings with Group 1 (best) performers being: Clinical Pharmacology, Micromedex, Facts & Comparisons 4.0, Lexi-Comp Online, Group 2: Epocrates Premium and RxList.com and Group 3: Epocrates Free (p < 0.05). Completeness scores were similarly stratified. Collapsing the databases into two groups by access (subscription or free), showed the subscription databases performed better than the free databases in the measured criteria (p < 0.001). CONCLUSION: Online drug information databases, which belong to clinical decision support, vary in their ability to answer questions across a range of categories

Ability of online drug databases to assist in clinical decision-making with infectious disease therapies

<p>Abstract</p> <p>Background</p> <p>Infectious disease (ID) is a dynamic field with new guidelines being adopted at a rapid rate. Clinical decision support tools (CDSTs) have proven beneficial in selecting treatment options to improve outcomes. However, there is a dearth of information on the abilities of CDSTs, such as drug information databases. This study evaluated online drug information databases when answering infectious disease-specific queries.</p> <p>Methods</p> <p>Eight subscription drug information databases: American Hospital Formulary Service Drug Information (AHFS), Clinical Pharmacology (CP), Epocrates Online Premium (EOP), Facts & Comparisons 4.0 Online (FC), Lexi-Comp (LC), Lexi-Comp with AHFS (LC-AHFS), Micromedex (MM), and PEPID PDC (PPDC) and six freely accessible: DailyMed (DM), DIOne (DIO), Epocrates Online Free (EOF), Internet Drug Index (IDI), Johns Hopkins ABX Guide (JHAG), and Medscape Drug Reference (MDR) were evaluated for their scope (presence of an answer) and completeness (on a 3-point scale) in answering 147 infectious disease-specific questions. Questions were divided among five classifications: antibacterial, antiviral, antifungal, antiparasitic, and vaccination/immunization. Classifications were further divided into categories (e.g., dosage, administration, emerging resistance, synergy, and spectrum of activity). Databases were ranked based on scope and completeness scores. ANOVA and Chi-square were used to determine differences between individual databases and between subscription and free databases.</p> <p>Results</p> <p>Scope scores revealed three discrete tiers of database performance: Tier 1 (82-77%), Tier 2 (73-65%) and Tier 3 (56-41%) which were significantly different from each other (p < 0.05). The top tier performers: MM (82%), MDR (81%), LC-AHFS (81%), AHFS (78%), and CP (77%) answered significantly more questions compared to other databases (p < 0.05). Top databases for completeness were: MM (97%), DM (96%), IDI (95%), and MDR (95%). Subscription databases performed better than free databases in all categories (p = 0.03). Databases suffered from 37 erroneous answers for an overall error rate of 1.8%.</p> <p>Conclusion</p> <p>Drug information databases used in ID practice as CDSTs can be valuable resources. MM, MDR, LC-AHFS, AHFS, and CP were shown to be superior in their scope and completeness of information, and MM, AHFS, and MDR provided no erroneous answers. There is room for improvement in all evaluated databases.</p

A comprehensive characterization of ice nucleation by three different types of cellulose particles immersed in water

We present the laboratory results of immersion freezing efficiencies of cellulose particles at supercooled temperature (T) conditions. Three types of chemically homogeneous cellulose samples are used as surrogates that represent supermicron and submicron ice-nucleating plant structural polymers. These samples include microcrystalline cellulose (MCC), fibrous cellulose (FC) and nanocrystalline cellulose (NCC). Our immersion freezing dataset includes data from various ice nucleation measurement techniques available at 17 different institutions, including nine dry dispersion and 11 aqueous suspension techniques. With a total of 20 methods, we performed systematic accuracy and precision analysis of measurements from all 20 measurement techniques by evaluating T-binned (1 ∘C) data over a wide T range (−36 ∘C <T<−4 ∘C). Specifically, we intercompared the geometric surface area-based ice nucleation active surface site (INAS) density data derived from our measurements as a function of T, ns,geo(T). Additionally, we also compared the ns,geo(T) values and the freezing spectral slope parameter (Δlog(ns,geo)/ΔT) from our measurements to previous literature results. Results show all three cellulose materials are reasonably ice active. The freezing efficiencies of NCC samples agree reasonably well, whereas the diversity for the other two samples spans ≈ 10 ∘C. Despite given uncertainties within each instrument technique, the overall trend of the ns,geo(T) spectrum traced by the T-binned average of measurements suggests that predominantly supermicron-sized cellulose particles (MCC and FC) generally act as more efficient ice-nucleating particles (INPs) than NCC with about 1 order of magnitude higher ns,geo(T)

The Two-Component Signal Transduction System CopRS of Corynebacterium glutamicum Is Required for Adaptation to Copper-Excess Stress

Copper is an essential cofactor for many enzymes but at high concentrations it is toxic for the cell. Copper ion concentrations ≥50 µM inhibited growth of Corynebacterium glutamicum. The transcriptional response to 20 µM Cu2+ was studied using DNA microarrays and revealed 20 genes that showed a ≥ 3-fold increased mRNA level, including cg3281-cg3289. Several genes in this genomic region code for proteins presumably involved in the adaption to copper-induced stress, e. g. a multicopper oxidase (CopO) and a copper-transport ATPase (CopB). In addition, this region includes the copRS genes (previously named cgtRS9) which encode a two-component signal transduction system composed of the histidine kinase CopS and the response regulator CopR. Deletion of the copRS genes increased the sensitivity of C. glutamicum towards copper ions, but not to other heavy metal ions. Using comparative transcriptome analysis of the ΔcopRS mutant and the wild type in combination with electrophoretic mobility shift assays and reporter gene studies the CopR regulon and the DNA-binding motif of CopR were identified. Evidence was obtained that CopR binds only to the intergenic region between cg3285 (copR) and cg3286 in the genome of C. glutamicum and activates expression of the divergently oriented gene clusters cg3285-cg3281 and cg3286-cg3289. Altogether, our data suggest that CopRS is the key regulatory system in C. glutamicum for the extracytoplasmic sensing of elevated copper ion concentrations and for induction of a set of genes capable of diminishing copper stress

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FdR – Publicaties niet-programma gebonde

The study of atmospheric ice-nucleating particles via microfluidically generated droplets

Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10³–10⁶ ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UK’s annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies

Two-component signal transduction in Corynebacterium glutamicum and other corynebacteria: on the way towards stimuli and targets

In bacteria, adaptation to changing environmental conditions is often mediated by two-component signal transduction systems. In the prototypical case, a specific stimulus is sensed by a membrane-bound histidine kinase and triggers autophosphorylation of a histidine residue. Subsequently, the phosphoryl group is transferred to an aspartate residue of the cognate response regulator, which then becomes active and mediates a specific response, usually by activating and/or repressing a set of target genes. In this review, we summarize the current knowledge on two-component signal transduction in Corynebacterium glutamicum. This Gram-positive soil bacterium is used for the large-scale biotechnological production of amino acids and can also be applied for the synthesis of a wide variety of other products, such as organic acids, biofuels, or proteins. Therefore, C. glutamicum has become an important model organism in industrial biotechnology and in systems biology. The type strain ATCC 13032 possesses 13 two-component systems and the role of five has been elucidated in recent years. They are involved in citrate utilization (CitAB), osmoregulation and cell wall homeostasis (MtrAB), adaptation to phosphate starvation (PhoSR), adaptation to copper stress (CopSR), and heme homeostasis (HrrSA). As C. glutamicum does not only face changing conditions in its natural environment, but also during cultivation in industrial bioreactors of up to 500 m3 volume, adaptability can also be crucial for good performance in biotechnological production processes. Detailed knowledge on two-component signal transduction and regulatory networks therefore will contribute to both the application and the systemic understanding of C. glutamicum and related species

The Fifth International Workshop on Ice Nucleation phase 2 (FIN-02): laboratory intercomparison of ice nucleation measurements

The second phase of the Fifth International Ice Nucleation Workshop (FIN-02) involved the gathering of a large number of researchers at the Karlsruhe Institute of Technology's Aerosol Interactions and Dynamics of the Atmosphere (AIDA) facility to promote characterization and understanding of ice nucleation measurements made by a variety of methods used worldwide. Compared to the previous workshop in 2007, participation was doubled, reflecting a vibrant research area. Experimental methods involved sampling of aerosol particles by direct processing ice nucleation measuring systems from the same volume of air in separate experiments using different ice nucleating particle (INP) types, and collections of aerosol particle samples onto filters or into liquid for sharing amongst measurement techniques that post-process these samples. In this manner, any errors introduced by differences in generation methods when samples are shared across laboratories were mitigated. Furthermore, as much as possible, aerosol particle size distribution was controlled so that the size limitations of different methods were minimized. The results presented here use data from the workshop to assess the comparability of immersion freezing measurement methods activating INPs in bulk suspensions, methods that activate INPs in condensation and/or immersion freezing modes as single particles on a substrate, continuous flow diffusion chambers (CFDCs) directly sampling and processing particles well above water saturation to maximize immersion and subsequent freezing of aerosol particles, and expansion cloud chamber simulations in which liquid cloud droplets were first activated on aerosol particles prior to freezing. The AIDA expansion chamber measurements are expected to be the closest representation to INP activation in atmospheric cloud parcels in these comparisons, due to exposing particles freely to adiabatic cooling. The different particle types used as INPs included the minerals illite NX and potassium feldspar (K-feldspar), two natural soil dusts representative of arable sandy loam (Argentina) and highly erodible sandy dryland (Tunisia) soils, respectively, and a bacterial INP (Snomax®). Considered together, the agreement among post-processed immersion freezing measurements of the numbers and fractions of particles active at different temperatures following bulk collection of particles into liquid was excellent, with possible temperature uncertainties inferred to be a key factor in determining INP uncertainties. Collection onto filters for rinsing versus directly into liquid in impingers made little difference. For methods that activated collected single particles on a substrate at a controlled humidity at or above water saturation, agreement with immersion freezing methods was good in most cases, but was biased low in a few others for reasons that have not been resolved, but could relate to water vapor competition effects. Amongst CFDC-style instruments, various factors requiring (variable) higher supersaturations to achieve equivalent immersion freezing activation dominate the uncertainty between these measurements, and for comparison with bulk immersion freezing methods. When operated above water saturation to include assessment of immersion freezing, CFDC measurements often measured at or above the upper bound of immersion freezing device measurements, but often underestimated INP concentration in comparison to an immersion freezing method that first activates all particles into liquid droplets prior to cooling (the PIMCA-PINC device, or Portable Immersion Mode Cooling chAmber–Portable Ice Nucleation Chamber), and typically slightly underestimated INP number concentrations in comparison to cloud parcel expansions in the AIDA chamber; this can be largely mitigated when it is possible to raise the relative humidity to sufficiently high values in the CFDCs, although this is not always possible operationally. Correspondence of measurements of INPs among direct sampling and post-processing systems varied depending on the INP type. Agreement was best for Snomax® particles in the temperature regime colder than −10 ∘C, where their ice nucleation activity is nearly maximized and changes very little with temperature. At temperatures warmer than −10 ∘C, Snomax® INP measurements (all via freezing of suspensions) demonstrated discrepancies consistent with previous reports of the instability of its protein aggregates that appear to make it less suitable as a calibration INP at these temperatures. For Argentinian soil dust particles, there was excellent agreement across all measurement methods; measures ranged within 1 order of magnitude for INP number concentrations, active fractions and calculated active site densities over a 25 to 30 ∘C range and 5 to 8 orders of corresponding magnitude change in number concentrations. This was also the case for all temperatures warmer than −25 ∘C in Tunisian dust experiments. In contrast, discrepancies in measurements of INP concentrations or active site densities that exceeded 2 orders of magnitude across a broad range of temperature measurements found at temperatures warmer than −25 ∘C in a previous study were replicated for illite NX. Discrepancies also exceeded 2 orders of magnitude at temperatures of −20 to −25 ∘C for potassium feldspar (K-feldspar), but these coincided with the range of temperatures at which INP concentrations increase rapidly at approximately an order of magnitude per 2 ∘C cooling for K-feldspar. These few discrepancies did not outweigh the overall positive outcomes of the workshop activity, nor the future utility of this data set or future similar efforts for resolving remaining measurement issues. Measurements of the same materials were repeatable over the time of the workshop and demonstrated strong consistency with prior studies, as reflected by agreement of data broadly with parameterizations of different specific or general (e.g., soil dust) aerosol types. The divergent measurements of the INP activity of illite NX by direct versus post-processing methods were not repeated for other particle types, and the Snomax® data demonstrated that, at least for a biological INP type, there is no expected measurement bias between bulk collection and direct immediately processed freezing methods to as warm as −10 ∘C. Since particle size ranges were limited for this workshop, it can be expected that for atmospheric populations of INPs, measurement discrepancies will appear due to the different capabilities of methods for sampling the full aerosol size distribution, or due to limitations on achieving sufficient water supersaturations to fully capture immersion freezing in direct processing instruments. Overall, this workshop presents an improved picture of present capabilities for measuring INPs than in past workshops, and provides direction toward addressing remaining measurement issues