Medication-related interventions to improve medication safety and patient outcomes on transition from adult intensive care settings : a systematic review and meta-analysis

Background Patients recovering from an episode in an intensive care unit (ICU) frequently experience medication errors on transition to the hospital ward. Structured handover recommendations often underestimate the challenges and complexity of ICU patient transitions. For adult ICU patients transitioning to a hospital ward, it is currently unclear what interventions reduce the risks of medication errors. The aims were to examine the impact of medication-related interventions on medication and patient outcomes on transition from adult ICU settings and identify barriers and facilitators to implementation. Methods The systematic review protocol was preregistered on PROSPERO. Six electronic databases were searched until October 2020 for controlled and uncontrolled study designs that reported medication-related (ie, de-prescribing; medication errors) or patient-related outcomes (ie, mortality; length of stay). Risk of bias (RoB) assessment used V.2.0 and ROBINS-I Cochrane tools. Where feasible, random-effects meta-analysis was used for pooling the OR across studies. The quality of evidence was assessed by Grading of Recommendations, Assessment, Development and Evaluations. Results Seventeen studies were eligible, 15 (88%) were uncontrolled before-after studies. The intervention components included education of staff (n=8 studies), medication review (n=7), guidelines (n=6), electronic transfer/handover tool or letter (n=4) and medicines reconciliation (n=4). Overall, pooled analysis of all interventions reduced risk of inappropriate medication continuation at ICU discharge (OR=0.45 (95% CI 0.31 to 0.63), I2=55%, n=9) and hospital discharge (OR=0.39 (95% CI 0.2 to 0.76), I2=75%, n=9). Multicomponent interventions, based on education of staff and guidelines, demonstrated no significant difference in inappropriate medication continuation at the ICU discharge point (OR 0.5 (95% CI 0.22 to 1.11), I2=62%, n=4), but were very effective in increasing de-prescribing outcomes on hospital discharge (OR 0.26 (95% CI 0.13 to 0.55), I2=67%, n=6)). Facilitators to intervention delivery included ICU clinical pharmacist availability and participation in multiprofessional ward rounds, while barriers included increased workload associated with the discharge intervention process. Conclusions Multicomponent interventions based on education of staff and guidelines were effective at achieving almost four times more de-prescribing of inappropriate medication by the time of patient hospital discharge. Based on the findings, practice and policy recommendations are made and guidance is provided on the need for, and design of theory informed interventions in this area, including the requirement for process and economic evaluations

A novel LC–ESI-MS method for the simultaneous determination of etravirine, darunavir and ritonavir in human blood plasma

The new potent combination of antiretrovirals etravirine, darunavir, and ritonavir requires a new bioanalytical method for clinical pharmacology investigations and potential therapeutic drug monitoring. The development and validation of a novel LC–MS method for the simultaneous quantification of the most recently FDA-approved protease inhibitor and non-nucleoside reverse transcriptase inhibitor is described. This novel method was developed and validated using a sub-2 μm particle column, and provides excellent chromatographic separation and peak shape for all three analytes and internal standard. The method was validated over the range of 0.002–2.0 μg/mL. Intra- and inter-day accuracy of all analytes ranged from 88 to 106%, and intra- and inter-day precision was <7%. Dilution of samples 2-, 5-, and 10-fold maintained accuracy and precision, using a sample volume as low as 10 μL. Finally, the applicability of the method was investigated with clinical samples and external quality assurance proficiency testing samples

A jump-growth model for predator-prey dynamics: derivation and application to marine ecosystems

This paper investigates the dynamics of biomass in a marine ecosystem. A stochastic process is defined in which organisms undergo jumps in body size as they catch and eat smaller organisms. Using a systematic expansion of the master equation, we derive a deterministic equation for the macroscopic dynamics, which we call the deterministic jump-growth equation, and a linear Fokker-Planck equation for the stochastic fluctuations. The McKendrick--von Foerster equation, used in previous studies, is shown to be a first-order approximation, appropriate in equilibrium systems where predators are much larger than their prey. The model has a power-law steady state consistent with the approximate constancy of mass density in logarithmic intervals of body mass often observed in marine ecosystems. The behaviours of the stochastic process, the deterministic jump-growth equation and the McKendrick--von Foerster equation are compared using numerical methods. The numerical analysis shows two classes of attractors: steady states and travelling waves.Comment: 27 pages, 4 figures. Final version as published. Only minor change

Functional performance of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold: a pre-clinical <i>in vitro</i> tribological study

Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus

Color Transparency versus Quantum Coherence in Electroproduction of Vector Mesons off Nuclei

So far no theoretical tool for the comprehensive description of exclusive electroproduction of vector mesons off nuclei at medium energies has been developed. We suggest a light-cone QCD formalism which is valid at any energy and incorporates formation effects (color transparency), the coherence length and the gluon shadowing. At medium energies color transparency (CT) and the onset of coherence length (CL) effects are not easily separated. Indeed, although nuclear transparency measured by the HERMES experiment rises with Q^2, it agrees with predictions of the vector dominance model (VDM) without any CT effects. Our new results and observations are: (i) the good agreement with the VDM found earlier is accidental and related to the specific correlation between Q^2 and CL for HERMES kinematics; (ii) CT effects are much larger than have been estimated earlier within the two channel approximation. They are even stronger at low than at high energies and can be easily identified by HERMES or at JLab; (iii) gluon shadowing which is important at high energies is calculated and included; (iv) our parameter-free calculations explain well available data for variation of nuclear transparency with virtuality and energy of the photon; (v) predictions for electroproduction of \rho and \phi are provided for future measurements at HERMES and JLab.Comment: Latex 57 pages and 17 figure

Differential penetration of raltegravir throughout gastrointestinal tissue: implications for eradication and cure

To investigate the concentration of the integrase strand inhibitor raltegravir (RAL) throughout gastrointestinal (GI) tissue, especially gutassociated lymphoid tissue (GALT), as an adjunct to current prevention and cure strategies

A Phenotype–Genotype Approach to Predicting CYP450 and P-Glycoprotein Drug Interactions With the Mixed Inhibitor/Inducer Tipranavir/Ritonavir

The effects of tipranavir/ritonavir (TPV/r) on hepatic and intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) enzyme activity were evaluated in 23 volunteers. The subjects received oral (p.o.) caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, and midazolam and digoxin (p.o. and intravenous (i.v.)) at baseline, during the first three doses of TPV/r (500 mg/200 mg b.i.d.), and at steady state. Plasma area under the curve (AUC)0–∞ and urinary metabolite ratios were used for quantification of protein activities. A single dose of TPV/r had no effect on the activity of CYP1A2 and CYP2C9; it weakly inhibited CYP2C19 and P-gp; and it potently inhibited CYP2D6 and CYP3A. Multiple dosing produced weak induction of CYP1A2, moderate induction of CYP2C19, potent induction of intestinal P-gp, and potent inhibition of CYP2D6 and CYP3A, with no significant effects on CYP2C9 and hepatic P-gp. Several P450/transporter single-nucleotide polymorphisms correlated with the baseline phenotype but not with the extent of inhibition or induction. Although mixed induction and inhibition are present, this approach offers an understanding of drug interaction mechanisms and ultimately assists in optimizing the clinical use of TPV/r

Genome-enabled insights into the biology of thrips as crop pests

Background The western flower thrips,Frankliniella occidentalis(Pergande), is a globally invasive pest and plant virus vector on a wide array of food, fiber, and ornamental crops. The underlying genetic mechanisms of the processes governing thrips pest and vector biology, feeding behaviors, ecology, and insecticide resistance are largely unknown. To address this gap, we present theF. occidentalisdraft genome assembly and official gene set.Results We report on the first genome sequence for any member of the insect order Thysanoptera. Benchmarking Universal Single-Copy Ortholog (BUSCO) assessments of the genome assembly (size = 415.8 Mb, scaffold N50 = 948.9 kb) revealed a relatively complete and well-annotated assembly in comparison to other insect genomes. The genome is unusually GC-rich (50%) compared to other insect genomes to date. The official gene set (OGS v1.0) contains 16,859 genes, of which similar to 10% were manually verified and corrected by our consortium. We focused on manual annotation, phylogenetic, and expression evidence analyses for gene sets centered on primary themes in the life histories and activities of plant-colonizing insects. Highlights include the following: (1) divergent clades and large expansions in genes associated with environmental sensing (chemosensory receptors) and detoxification (CYP4, CYP6, and CCE enzymes) of substances encountered in agricultural environments; (2) a comprehensive set of salivary gland genes supported by enriched expression; (3) apparent absence of members of the IMD innate immune defense pathway; and (4) developmental- and sex-specific expression analyses of genes associated with progression from larvae to adulthood through neometaboly, a distinct form of maturation differing from either incomplete or complete metamorphosis in the Insecta.Conclusions Analysis of theF. occidentalisgenome offers insights into the polyphagous behavior of this insect pest that finds, colonizes, and survives on a widely diverse array of plants. The genomic resources presented here enable a more complete analysis of insect evolution and biology, providing a missing taxon for contemporary insect genomics-based analyses. Our study also offers a genomic benchmark for molecular and evolutionary investigations of other Thysanoptera species.Animal science

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy