Improved outcomes and cost savings for patients with bleeding disorders: a quality improvement project.

Background: Providing optimal care for patients with bleeding disorders according to national standards remains a challenge at designated Hemophilia Treatment Centers (HTCs). Improved care may reduce bleeds and costs. Objectives: To improve care and demonstrate cost savings by 1) reducing preventable hospitalizations and emergency room visits (PHER) for bleeding, 2) increasing use of prophylaxis in severe hemophilia, and 3) improving patient-HTC communication and primary care engagement. Methods: Prospective quality improvement project using the Define, Measure, Analyze, Improve, and Control methodology to implement uniform guideline-based bleeding disorder care at a rural HTC (N = 88). Intervention used a standardized physician checklist, improved communication, and reserved physician time for urgent management. Outcomes were determined by retrospective chart review; urgent management was tracked prospectively. Results: Intervention significantly reduced PHER by 85.4%. Use of prophylaxis in persons with severe hemophilia increased from 58.8% to 100%; attainment of a primary care physician and electronic portal enrollment met outcomes for intervention success. HTC clinic visit attendance was low at 55.2%. The majority of patients (71.6%) had at least 1 outpatient urgent episode (mean, 0.72 episode per year), and 93% had nonurgent management (mean, 9.3 episodes per year) occurring outside of a clinic visit. Hospital PHER factor cost in the group was reduced by 94.5%, from $11,800 to $640 per patient per year-a cost savings of $982,088 yearly. Conclusion: This collaborative study shows that implementation of a carefully designed quality improvement project, such as uniform guidelines with focus on strengthening ambulatory management, led to improved outcomes and cost savings.

Real-Time Electronic Patient Portal Use Among Emergency Department Patients.

Importance: Patients with inequitable access to patient portals frequently present to emergency departments (EDs) for care. Little is known about portal use patterns among ED patients. Objectives: To describe real-time patient portal usage trends among ED patients and compare demographic and clinical characteristics between portal users and nonusers. Design, Setting, and Participants: In this cross-sectional study of 12 teaching and 24 academic-affiliated EDs from 8 health systems in California, Connecticut, Massachusetts, Ohio, Tennessee, Texas, and Washington, patient portal access and usage data were evaluated for all ED patients 18 years or older between April 5, 2021, and April 4, 2022. Exposure: Use of the patient portal during ED visit. Main Outcomes and Measures: The primary outcomes were the weekly proportions of ED patients who logged into the portal, viewed test results, and viewed clinical notes in real time. Pooled random-effects models were used to evaluate temporal trends and demographic and clinical characteristics associated with real-time portal use. Results: The study included 1 280 924 unique patient encounters (53.5% female; 0.6% American Indian or Alaska Native, 3.7% Asian, 18.0% Black, 10.7% Hispanic, 0.4% Native Hawaiian or Pacific Islander, 66.5% White, 10.0% other race, and 4.0% with missing race or ethnicity; 91.2% English-speaking patients; mean [SD] age, 51.9 [19.2] years). During the study, 17.4% of patients logged into the portal while in the ED, whereas 14.1% viewed test results and 2.5% viewed clinical notes. The odds of accessing the portal (odds ratio [OR], 1.36; 95% CI, 1.19-1.56), viewing test results (OR, 1.63; 95% CI, 1.30-2.04), and viewing clinical notes (OR, 1.60; 95% CI, 1.19-2.15) were higher at the end of the study vs the beginning. Patients with active portal accounts at ED arrival had a higher odds of logging into the portal (OR, 17.73; 95% CI, 9.37-33.56), viewing test results (OR, 18.50; 95% CI, 9.62-35.57), and viewing clinical notes (OR, 18.40; 95% CI, 10.31-32.86). Patients who were male, Black, or without commercial insurance had lower odds of logging into the portal, viewing results, and viewing clinical notes. Conclusions and Relevance: These findings suggest that real-time patient portal use during ED encounters has increased over time, but disparities exist in portal access that mirror trends in portal usage more generally. Given emergency medicine's role in caring for medically underserved patients, there are opportunities for EDs to enroll and train patients in using patient portals to promote engagement during and after their visits.

Circadian variation in muscle force output in males using isokinetic, isometric dynamometry: can we observe this in multi-joint movements using the muscleLab force-velocity encoder and are they similar in peak and magnitude?

We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (Trec, Tm) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s-1 for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, Trec and Tm were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for Trec and Tm at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C, p < 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h (p < 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Genomics-informed captive breeding can reduce inbreeding depression and the genetic load in zoo populations.

Zoo populations of threatened species are a valuable resource for the restoration of wild populations. However, their small effective population size poses a risk to long-term viability, especially in species with high genetic load. Recent bioinformatic developments can identify harmful genetic variants in genome data. Here, we advance this approach, analysing the genetic load in the threatened pink pigeon (Nesoenas mayeri). We lifted the mutation-impact scores that had been calculated for the chicken (Gallus gallus) to estimate the genetic load in six pink pigeons. Additionally, we perform in silico crossings to predict the genetic load and realized load of potential offspring. We thus identify the optimal mate pairs that are theoretically expected to produce offspring with the least inbreeding depression. We use computer simulations to show how genomics-informed conservation can reduce the genetic load whilst reducing the loss of genome-wide diversity. Genomics-informed management is likely to become instrumental in maintaining the long-term viability of zoo populations.

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction.

Blood cell phenotypes are routinely tested in healthcare to inform clinical decisions. Genetic variants influencing mean blood cell phenotypes have been used to understand disease aetiology and improve prediction; however, additional information may be captured by genetic effects on observed variance. Here, we mapped variance quantitative trait loci (vQTL), i.e. genetic loci associated with trait variance, for 29 blood cell phenotypes from the UK Biobank (N~408,111). We discovered 176 independent blood cell vQTLs, of which 147 were not found by additive QTL mapping. vQTLs displayed on average 1.8-fold stronger negative selection than additive QTL, highlighting that selection acts to reduce extreme blood cell phenotypes. Variance polygenic scores (vPGSs) were constructed to stratify individuals in the INTERVAL cohort (N~40,466), where genetically less variable individuals (low vPGS) had increased conventional PGS accuracy (by ~19%) than genetically more variable individuals. Genetic prediction of blood cell traits improved by ~10% on average combining PGS with vPGS. Using Mendelian randomisation and vPGS association analyses, we found that alcohol consumption significantly increased blood cell trait variances highlighting the utility of blood cell vQTLs and vPGSs to provide novel insight into phenotype aetiology as well as improve prediction.

Unveiling the genetic blueprint of a desert scorpion: A chromosome-level genome of Hadrurus arizonensis provides the first reference for Parvorder Iurida.

Over 400 million years old, scorpions represent an ancient group of arachnids and one of the first animals to adapt to life on land. Presently, the lack of available genomes within scorpions hinders research on their evolution. This study leverages ultra-long nanopore sequencing and Pore-C to generate the first chromosome level assembly and annotation for the desert hairy scorpion, Hadrurus arizonensis. The assembled genome is 2.23 Gb in size with an N50 of 280 Mb. Pore-C scaffolding re-oriented 99.6% of bases into nine chromosomes and BUSCO identified 998 (98.6%) complete arthropod single copy orthologs. Repetitive elements represent 54.69% of the assembled bases, including 872,874 (29.39%) LINE elements. A total of 18,996 protein-coding genes and 75,256 transcripts were predicted, and extracted protein sequences yielded a BUSCO score of 97.2%. This is the first genome assembled and annotated within the family Hadruridae, representing a crucial resource for closing gaps in genomic knowledge of scorpions, resolving arachnid phylogeny, and advancing studies in comparative and functional genomics.

Effectiveness of Preoperative Alpha Wave Entrainment in Pediatric Dental Patients: A Randomized Controlled Trial.

Background Pediatric dental anxiety is a significant barrier to effective dental care, necessitating non-pharmacological interventions. Alpha wave entrainment has shown promise in adult studies for reducing procedural anxiety and pain perception, but its effectiveness in pediatric dental settings remains underexplored. Objective This study aims to evaluate the effectiveness of preoperative alpha wave entrainment in alleviating anxiety in gender-specific participants to the interventions. Methods We conducted a randomized controlled trial involving 252 pediatric patients (aged 7-12) with cooperative dispositions. Participants were randomly assigned to either an experimental group receiving alpha wave entrainment or a control group receiving conventional behavior management techniques. The experimental intervention involved 10-minute sessions of binaural beats with visual stimulation designed to induce alpha-wave synchronization. Anxiety levels were assessed using physiological measures (heart rate and blood pressure), both pre- and post-interventions. Results The intervention group demonstrated a significant reduction in heart rate and systolic blood pressure post-intervention compared to the control group. These changes indicate a decrease in anxiety levels, with no significant gender differences in the response to the intervention. Conclusion Alpha wave entrainment effectively reduces dental anxiety in pediatric patients, with similar efficacy observed across genders. This study supports the incorporation of alpha wave entrainment into pediatric dental practices as a viable alternative to traditional anxiety management techniques.

Experimental and Computational Study of Pyrogenic Carbonaceous Matter Facilitated Hydrolysis of 2,4-Dinitroanisole (DNAN).

This study investigated the reaction pathway of 2,4-dinitroanisole (DNAN) on the pyrogenic carbonaceous matter (PCM) to assess the scope and mechanism of PCM-facilitated surface hydrolysis. DNAN degradation was observed at pH 11.5 and 25 °C with a model PCM, graphite, whereas no significant decay occurred without graphite. Experiments were performed at pH 11.5 due to the lack of DNAN decay at pH below 11.0, which was consistent with previous studies. Graphite exhibited a 1.78-fold enhancement toward DNAN decay at 65 °C and pH 11.5 relative to homogeneous solution by lowering the activation energy for DNAN hydrolysis by 54.3 ± 3.9%. This is supported by our results from the computational modeling using Car-Parrinello simulations by ab initio molecular dynamics/molecular mechanics (AIMD/MM) and DFT free energy simulations, which suggest that PCM effectively lowered the reaction barriers by approximately 8 kcal mol-1 compared to a homogeneous solution. Quaternary ammonium (QA)-modified activated carbon performed the best among several PCMs by reducing DNAN half-life from 185 to 2.5 days at pH 11.5 and 25 °C while maintaining its reactivity over 10 consecutive additions of DNAN. We propose that PCM can affect the thermodynamics and kinetics of hydrolysis reactions by confining the reaction species near PCM surfaces, thus making them less accessible to solvent molecules and creating an environment with a weaker dielectric constant that favors nucleophilic substitution reactions. Nitrite formation during DNAN decay confirmed a denitration pathway, whereas demethylation, the preferred pathway in homogeneous solution, produces 2,4-dinitrophenol (DNP). Denitration catalyzed by PCM is advantageous to demethylation because nitrite is less toxic than DNAN and DNP. These findings provide critical insights for reactive adsorbent design that has broad implications for catalyst design and pollutant abatement.

Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput.

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here we describe the high-throughput, functional assessment of phosphorylation sites through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of PHLPP1, which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.

The presence of fear: How subjective fear, not physiological changes, shapes the experience of presence.

When we become engrossed in novels, films, games, or even our own wandering thoughts, we can feel present in a reality distinct from the real world. Although this subjective sense of presence is, presumably, a ubiquitous aspect of conscious experience, the mechanisms that produce it are unknown. Correlational studies conducted in virtual reality have shown that we feel more present when we are afraid, motivating claims that physiological changes contribute to presence; however, such causal claims remain to be evaluated. Here, we report two experiments that test the causal role of subjective and physiological components of fear (i.e., activation of the sympathetic nervous system) in generating presence. In Study 1, we validated a virtual reality simulation capable of inducing fear. Participants rated their emotions while they crossed a wooden plank that appeared to be suspended above a city street; at the same time, we recorded heart rate and skin conductance levels. Height exposure increased ratings of fear, presence, and both measures of sympathetic activation. Although presence and fear ratings were correlated during height exposure, presence and sympathetic activation were unrelated. In Study 2, we manipulated whether the plank appeared at height or at ground level. We also captured participants' movements, which revealed that alongside increases in subjective fear, presence, and sympathetic activation, participants also moved more slowly at height relative to controls. Using a mediational approach, we found that the relationship between height exposure and presence on the plank was fully mediated by self-reported fear, and not by sympathetic activation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine.

Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.

Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice.

A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer's disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice. From 6-12 months of age, male and female APP/PS1 and C57BL/6 mice were chronically housed at 23 or 30°C. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and spatial cognition. Plasma, hippocampal, and peripheral (adipose, hepatic, and skeletal muscle) samples were procured postmortem and tissue-specific markers of amyloid accumulation, metabolism, and inflammation were assayed. Chronic 30°C exposure increased Tc in all groups except female APP/PS1 mice. All mice receiving thermotherapy had either improved glucose tolerance or insulin sensitivity, but the underlying processes responsible for these effects varied across sexes. In males, glucose regulation was influenced predominantly by hormonal signaling in plasma and skeletal muscle glucose transporter 4 expression, whereas in females, this was modulated at the tissue level. Thermotherapy improved spatial navigation in male C57BL/6 and APP/PS1 mice, with the later attributed to reduced hippocampal soluble amyloid-ß (Aß)42. Female APP/PS1 mice exhibited worse spatial memory recall after chronic thermotherapy. Together, the data highlights the metabolic benefits of passive thermotherapy with potential nonpharmacological management for some individuals with AD, and provides further evidence for the necessity of adopting personalized patient care.

Pattern of Clinical and Laboratory Presentation of Cerebral Malaria among Children in Nigeria.

Introduction: Cerebral malaria (CM) is the most lethal form of severe malaria with high case fatality rates. Overtime, there is an inherent risk in changing pattern of presentation of CM which, if the diagnosis is missed due to these changing factors, may portend a poor outcome. Variations in the pattern of clinic-laboratory presentations also make generalization difficult. This study was, therefore, set out to report the pattern of clinical and laboratory presentation of CM. Methods: This was a cross-sectional study among children aged 6 months to 14 years admitted with a diagnosis of CM as defined by the World Health Organization criteria. A pretested pro forma was filled, and detailed neurological examination and laboratory (biochemical, microbiology, and hematology) investigations were done. P <5% was considered statistically significant. Results: Sixty-four children were recruited with a mean age of 34.9 ± 24.9 months and a male-to-female ratio of 1.9:1. There were 87.5% of under-five children. Fever (96.9%) was the major presenting feature closely followed by convulsions (92.2%). Convulsions were mainly generalized (94.9%) and multiple (76.5%). Profound coma (Blantyre coma score of 0) was present in 12.5% of cases, and the leading features on examination were fever (84.4%) and pallor (75.0%). Retinal vessel whitening (48.4%) was the most common funduscopic abnormality. Metabolic acidosis (47.9%), severe anemia (14.1%), hyperglycemia (17.2%), and hypoglycemia (7.8%) were seen among the children. Few (1.6%) had hyperparasitemia and bacteremia (3.2%). Conclusion: Early recognition of the clinical presentation and prompt management may improve the outcome of cerebral malaria.

Quantification of Hydrogen Isotopes Utilizing Raman Spectroscopy Paired with Chemometric Analysis for Application across Multiple Systems.

Online and real-time analysis of a chemical process is a major analytical challenge that can drastically change the way the chemical industry or chemical research operates. With in situ analyses, a new and powerful understanding of chemistry can be gained; however, building robust tools for long-term monitoring faces many challenges, including compensating for instrument drift, instrument replacement, and sensor or probe replacement. Accounting for these changes by recollecting calibration data and rebuilding quantification models can be costly and time-consuming. Here, methods to overcome these challenges are demonstrated with an application of Raman spectroscopy to monitoring hydrogen isotopes with varied speciation within dynamic gas streams. Specifically, chemical data science tools such as chemometric modeling are leveraged along with several examples of calibration transfer approaches. Furthermore, the optimization of instrument and sensor cell parameters for targeted gas-phase analyses is discussed. While the particular focus on hydrogen is highly beneficial within the nuclear energy sector, mechanisms built and demonstrated here are widely applicable to optical spectroscopy monitoring in numerous other chemical systems that can be leveraged in other processes.

Why animals can outrun robots.

Animals are much better at running than robots. The difference in performance arises in the important dimensions of agility, range, and robustness. To understand the underlying causes for this performance gap, we compare natural and artificial technologies in the five subsystems critical for running: power, frame, actuation, sensing, and control. With few exceptions, engineering technologies meet or exceed the performance of their biological counterparts. We conclude that biology's advantage over engineering arises from better integration of subsystems, and we identify four fundamental obstacles that roboticists must overcome. Toward this goal, we highlight promising research directions that have outsized potential to help future running robots achieve animal-level performance.

IMPROVE: a feature model to predict neoepitope immunogenicity through broad-scale validation of T-cell recognition.

Background: Mutation-derived neoantigens are critical targets for tumor rejection in cancer immunotherapy, and better tools for neoepitope identification and prediction are needed to improve neoepitope targeting strategies. Computational tools have enabled the identification of patient-specific neoantigen candidates from sequencing data, but limited data availability has hindered their capacity to predict which of the many neoepitopes will most likely give rise to T cell recognition. Method: To address this, we make use of experimentally validated T cell recognition towards 17,500 neoepitope candidates, with 467 being T cell recognized, across 70 cancer patients undergoing immunotherapy. Results: We evaluated 27 neoepitope characteristics, and created a random forest model, IMPROVE, to predict neoepitope immunogenicity. The presence of hydrophobic and aromatic residues in the peptide binding core were the most important features for predicting neoepitope immunogenicity. Conclusion: Overall, IMPROVE was found to significantly advance the identification of neoepitopes compared to other current methods.

Role of a Pharmacist in Postdischarge Care for Patients With Kidney Disease: A Scoping Review.

OBJECTIVE: The objective was to explore and describe the role of pharmacists in providing postdischarge care to patients with kidney disease. DATA SOURCES: PubMed, Embase (Elsevier), CINAHL (Ebscohost), Web of Science Core Collection, and Scopus were searched on January 30, 2023. Publication date limits were not included. Search terms were identified based on 3 concepts: kidney disease, pharmacy services, and patient discharge. Experimental, quasi-experimental, observational, and qualitative studies, or study protocols, describing the pharmacist's role in providing postdischarge care for patients with kidney disease, excluding kidney transplant recipients, were eligible. STUDY SELECTION AND DATA EXTRACTION: Six unique interventions were described in 10 studies meeting inclusion criteria. DATA SYNTHESIS: Four interventions targeted patients with acute kidney injury (AKI) during hospitalization and 2 evaluated patients with pre-existing chronic kidney disease. Pharmacists were a multidisciplinary care team (MDCT) member in 5 interventions and were the sole provider in 1. Roles commonly identified include medication review, medication reconciliation, medication action plan formation, kidney function assessment, drug dose adjustments, and disease education. Some studies showed improvements in diagnostic coding, laboratory monitoring, medication therapy problem (MTP) resolution, and patient education; prevention of hospital readmission was inconsistent. Limitations include lack of standardized reporting of kidney disease, transitions of care processes, and differences in outcomes evaluated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review identifies potential roles of a pharmacist as part of a postdischarge MDCT for patients with varying degrees of kidney disease. CONCLUSIONS: The pharmacist's role in providing postdischarge care to patients with kidney disease is inconsistent. Multidisciplinary care teams including a pharmacist provided consistent identification and resolution of MTPs, improved patient education, and increased self-awareness of diagnosis.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.

The Drosophila Hippo pathway transcription factor Scalloped and its co-factors alter each other's chromatin binding dynamics and transcription in vivo.

The Hippo pathway is an important regulator of organ growth and cell fate. The major mechanism by which Hippo is known to control transcription is by dictating the nucleo-cytoplasmic shuttling rate of Yorkie, a transcription co-activator, which promotes transcription with the DNA binding protein Scalloped. The nuclear biophysical behavior of Yorkie and Scalloped, and whether this is regulated by the Hippo pathway, remains unexplored. Using multiple live-imaging modalities on Drosophila tissues, we found that Scalloped interacts with DNA on a broad range of timescales, and enrichment of Scalloped at sites of active transcription is mediated by longer DNA dwell times. Further, Yorkie increased Scalloped's DNA dwell time, whereas the repressors Nervous fingers 1 (Nerfin-1) and Tondu-domain-containing growth inhibitor (Tgi) decreased it. Therefore, the Hippo pathway influences transcription not only by controlling nuclear abundance of Yorkie but also by modifying the DNA binding kinetics of the transcription factor Scalloped.