There is Only One Valid Definition of Clearance: Critical Examination of Clearance Concepts Reveals the Potential for Errors in Clinical Drug Dosing Decisions.
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ABSTRACT:
SUBMITTER: Benet LZ
PROVIDER: S-EPMC8110503 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios. METHODS:We conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5?years' experience. Outcomes were underlying principles of drug dosing, and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios. RESULTS:Forty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Altough there remained much uncertainty in defining dosing error, expert clinicians agreed that, for most medication categories and clinical scenarios, dosing over or below 10% of reference range was considered an error threshold. CONCLUSION:Dosing principles and threshold are complex in pediatric critical care, and expert clinicians were uncertain about whether many scenarios were considered in error. For most intermittent medications, dosing over 10% below or above reference range was considered a dosing error, although this was largely influenced by clinical context and drug properties. This consensus driven error threshold will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.
| S-EPMC7576795 | biostudies-literature
Project description:The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term "microbiome." Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role. Video Abstract.
| S-EPMC7329523 | biostudies-literature
Project description:In 1997, the American Medical Informatics Association proposed a US information strategy that included a population health record (PopHR). Despite subsequent progress on the conceptualization, development, and implementation of electronic health records and personal health records, minimal progress has occurred on the PopHR. Adapting International Organization for Standarization electronic health records standards, we define the PopHR as a repository of statistics, measures, and indicators regarding the state of and influences on the health of a defined population, in computer processable form, stored and transmitted securely, and accessible by multiple authorized users. The PopHR is based upon an explicit population health framework and a standardized logical information model. PopHR purpose and uses, content and content sources, functionalities, business objectives, information architecture, and system architecture are described. Barriers to implementation and enabling factors and a three-stage implementation strategy are delineated.
| S-EPMC2995645 | biostudies-literature
Project description:In the last decades much effort was put in understanding fouling phenomena on membranes. One successful approach to describe fouling issues on membranes is the critical flux theory. The possibility to measure a maximum value of the permeate flux for a given system without incurring in fouling issues was a breakthrough in membrane process design. However, in many cases critical fluxes were found to be very low, lower than the economic feasibility of the process. The knowledge of the critical flux value must be therefore considered as a good starting point for process design. In the last years, a new concept was introduced, the threshold flux, which defines the maximum permeate flow rate characterized by a low constant fouling rate regime. This concept, more than the critical flux, is a new practical tool for membrane process designers. In this paper a brief review on critical and threshold flux will be reported and analyzed. And since the concepts share many common aspects, merged into a new concept, called the boundary flux, the validation will occur by the analysis of previously collected data by the authors, during the treatment of olive vegetation wastewater by ultrafiltration and nanofiltration membranes.
| S-EPMC3925542 | biostudies-other
Project description:Ischemic vascular disease is a major cause of mortality and morbidity worldwide, and regeneration of blood vessels in perfusion-deficient tissues is a worthwhile therapeutic goal. The idea of delivering endothelial stem/progenitor cells to repair damaged vasculature, reperfuse hypoxic tissue, prevent cell death, and consequently diminish tissue inflammation and fibrosis has a strong scientific basis and clinical value. Various labs have proposed endothelial stem/progenitor cell candidates. This has created confusion, as there are profound differences between these cell definitions based on isolation methodology, characterization, and reparative biology. Here, a stricter definition based on stem cell biology principles is proposed. Although preclinical studies have often been promising, results from clinical trials have been highly contradictory and served to highlight multiple challenges associated with disappointing therapeutic benefit. This article reviews recent accomplishments in the field and discusses current difficulties when developing endothelial stem cell therapies. Emerging evidence that disputes the classic view of the bone marrow as the source for these cells and supports the vascular wall as the niche for these tissue-resident endothelial stem cells is considered. In addition, novel markers to identify endothelial stem cells, including CD157, EPCR, and CD31low VEGFR2low IL33+ Sox9+ , are described.
| S-EPMC8560200 | biostudies-literature
Project description:Poorly designed labels and packaging are key contributors to medication errors. To identify attributes of labels and dosing tools that could be improved, we examined the extent to which dosing error rates are affected by tool characteristics (ie, type, marking complexity) and discordance between units of measurement on labels and dosing tools; along with differences by health literacy and language.Randomized controlled experiment in 3 urban pediatric clinics. English- or Spanish-speaking parents (n = 2110) of children ?8 years old were randomly assigned to 1 of 5 study arms and given labels and dosing tools that varied in unit pairings. Each parent measured 9 doses of medication (3 amounts [2.5, 5, and 7.5 mL] and 3 tools [1 cup, 2 syringes (0.2- and 0.5-mL increments)]), in random order. Outcome assessed was dosing error (>20% deviation; large error defined as > 2 times the dose).A total of 84.4% of parents made ?1 dosing error (21.0% ?1 large error). More errors were seen with cups than syringes (adjusted odds ratio = 4.6; 95% confidence interval, 4.2-5.1) across health literacy and language groups (P < .001 for interactions), especially for smaller doses. No differences in error rates were seen between the 2 syringe types. Use of a teaspoon-only label (with a milliliter and teaspoon tool) was associated with more errors than when milliliter-only labels and tools were used (adjusted odds ratio = 1.2; 95% confidence interval, 1.01-1.4).Recommending oral syringes over cups, particularly for smaller doses, should be part of a comprehensive pediatric labeling and dosing strategy to reduce medication errors.
| S-EPMC5051204 | biostudies-literature
Project description:Adaptive memory requires context-dependent control over how information is retrieved, evaluated and used to guide action, yet the signals that drive adjustments to memory decisions remain unknown. Here we show that prediction errors (PEs) coded by the striatum support control over memory decisions. Human participants completed a recognition memory test that incorporated biased feedback to influence participants' recognition criterion. Using model-based fMRI, we find that PEs-the deviation between the outcome and expected value of a memory decision-correlate with striatal activity and predict individuals' final criterion. Importantly, the striatal PEs are scaled relative to memory strength rather than the expected trial outcome. Follow-up experiments show that the learned recognition criterion transfers to free recall, and targeting biased feedback to experimentally manipulate the magnitude of PEs influences criterion consistent with PEs scaled relative to memory strength. This provides convergent evidence that declarative memory decisions can be regulated via striatally mediated reinforcement learning signals.
| S-EPMC5059768 | biostudies-literature
Project description:Background:The accuracy of drug dosing calculations during medical emergencies in children has not been evaluated extensively. The objectives of this study were to evaluate the accuracy of drug dose calculations using the Broselow tape, the PAWPER XL tape plus its companion drug-dosing guide, a custom-designed mobile phone app and no drug-dosing aid (control group). Methods:This was a prospective study in which 32 emergency medicine volunteers participated in eight simulations of common paediatric emergency conditions, using children models. The participants used the three methods to estimate the children's weight and calculate drug doses. The accuracy of and time taken for the drug dose determinations were then evaluated for each of the methods. Results:The overall accuracy of drug dose determinations was extremely and potentially dangerously low in the control group in which no dosing guide was used as well as in the Broselow tape group (<20% of doses were correct). The accuracy was significantly higher with the PAWPER XL tape group and the mobile app group (47% and 31% respectively). The times taken to obtain the required information did not differ in a clinically meaningful magnitude. Conclusions:Both an accurate weight estimation and a dosing guide with comprehensive information were necessary to produce an accurate prescription. The information on the Broselow tape was not sufficient for this purpose. The current guidelines recommending the use of tapes with limited information should be revised. The results from the comprehensive dosing guides were substantially better, but still had a lower proportion of accurate prescriptions than desirable. The role of training in every aspect of the emergency paediatric weight estimation and drug dosing procedure cannot be underestimated and should be routine in any environment where emergency care may be needed.
| S-EPMC7320197 | biostudies-literature
Project description:Perseveration is a well-replicated finding in autism. The aim of this study was to examine how the context of the task influences performance with respect to this phenomenon. We randomly assigned 137 children aged 6-12 with and without autism to complete a modified card-sorting task under one of two conditions: Children were either told the sorting rules on each trial (Explicit), or were given feedback to formulate the rules themselves (Implicit). While performance was enhanced on the Explicit condition for participants without autism, the participants with autism were disadvantaged by this manipulation. In contrast, there were few differences in performance between groups on the Implicit condition. Exploratory analyses were used to examine this unexpected result; increased autism symptomology was associated with poorer performance.
| S-EPMC7806145 | biostudies-literature
Project description:Poorly designed labels and dosing tools contribute to dosing errors. We examined the degree to which errors could be reduced with pictographic diagrams, milliliter-only units, and provision of tools more closely matched to prescribed volumes.This study involved a randomized controlled experiment in 3 pediatric clinics. English- and Spanish-speaking parents (n = 491) of children ?8 years old were randomly assigned to 1 of 4 groups and given labels and dosing tools that varied in label instruction format (text and pictogram, or text only) and units (milliliter-only ["mL"] or milliliter/teaspoon ["mL/tsp"]). Each parent measured 9 doses of liquid medication (3 amounts [2, 7.5, and 10 mL] and 3 tools [1 cup, 2 syringes (5- and 10-mL capacities)]) in random order. The primary outcome was dosing error (>20% deviation), and large error (>2× dose).We found that 83.5% of parents made ?1 dosing error (overdosing was present in 12.1% of errors) and 29.3% of parents made ?1 large error (>2× dose). The greatest impact on errors resulted from the provision of tools more closely matched to prescribed dose volumes. For the 2-mL dose, the fewest errors were seen with the 5-mL syringe (5- vs 10-mL syringe: adjusted odds ratio [aOR] = 0.3 [95% confidence interval: 0.2-0.4]; cup versus 10-mL syringe: aOR = 7.5 [5.7-10.0]). For the 7.5-mL dose, the fewest errors were with the 10-mL syringe, which did not necessitate measurement of multiple instrument-fulls (5- vs 10-mL syringe: aOR = 4.0 [3.0-5.4]; cup versus 10-mL syringe: aOR = 2.1 [1.5-2.9]). Milliliter/teaspoon was associated with more errors than milliliter-only (aOR = 1.3 [1.05-1.6]). Parents who received text only (versus text and pictogram) instructions or milliliter/teaspoon (versus milliliter-only) labels and tools made more large errors (aOR = 1.9 [1.1-3.3], aOR = 2.5 [1.4-4.6], respectively).Provision of dosing tools more closely matched to prescribed dose volumes is an especially promising strategy for reducing pediatric dosing errors.
| S-EPMC5495522 | biostudies-literature