The Impact of Prescription Time Limits on Phosphate Administration in the Intensive Care Unit: A Before-After Quality Improvement Study.

(1) Background: We aim to examine and improve phosphate prescribing as part of a quality assurance program by examining the change in the proportion of patients receiving phosphate with normal or high preceding serum phosphate concentrations before and after the introduction of the 24 h time limit to default phosphate prescription. (2) Methods: This was a quality assurance study conducted across three Australian adult intensive care units (ICUs). All adult patients with ICU lengths of stay greater than or equal to 48 h who had their serum phosphate concentrations measured were included. A 24 h time limit was introduced to the protocolised prescription in the electronic clinical information system for enteral and intravenous phosphate at participating ICUs. Patient characteristics, phosphate administration, and outcomes were compared before and after this time limit was introduced. The primary outcome was the proportion of patients to whom phosphate was prescribed after measurement of a normal or high serum phosphate level. Secondary outcomes were ICU length of stay, mortality, and discharge destination. (3) Results: A total of 1192 patients were included from three ICUs over the two periods. The proportion of patients with a normal or high measured phosphate level who then received phosphate supplementation was significantly lower in the second study period (30.3% vs. 9.9%; p < 0.001). This difference persisted when adjusted for potential confounders in a mixed-effects logistic regression model (an adjusted odds ratio for receiving phosphate with normal or high serum concentration 0.214, 95% confidence interval of 0.132-0.347; p < 0.001). No significant difference was seen in the typical ICU length of stay, in-hospital case-fatality rate, and hospital discharge destination between these groups. (4) Conclusions: This multicentre before-after study has demonstrated that the introduction of a 24 h limit on electronic phosphate prescriptions resulted in significantly fewer patients receiving phosphate when their serum phosphate concentration was normal or high, without any adverse impact on patient outcomes.

Interventions to improve patient admission and discharge practices in adult intensive care units: A systematic review.

OBJECTIVES: To identify and synthesise interventions and implementation strategies to optimise patient flow, addressing admission delays, discharge delays, and after-hours discharges in adult intensive care units. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Five electronic databases, including CINAHL, PubMed, Emcare, Scopus, and the Cochrane Library, were searched from 2007 to 2023 to identify articles describing interventions to enhance patient flow practices in adult intensive care units. The Critical Appraisal Skills Program (CASP) tool assessed the methodological quality of the included studies. All data was synthesised using a narrative approach. SETTING: Adult intensive care units. RESULTS: Eight studies met the inclusion criteria, mainly comprising quality improvement projects (n = 3) or before-and-after studies (n = 4). Intervention types included changing workflow processes, introducing decision support tools, publishing quality indicator data, utilising outreach nursing services, and promoting multidisciplinary communication. Various implementation strategies were used, including one-on-one training, in-person knowledge transfer, digital communication, and digital data synthesis and display. Most studies (n = 6) reported a significant improvement in at least one intensive care process-related outcome, although fewer studies specifically reported improvements in admission delays (0/0), discharge delays (1/2), and after-hours discharge (2/4). Two out of six studies reported significant improvements in patient-related outcomes after implementing the intervention. CONCLUSION: Organisational-level strategies, such as protocols and alert systems, were frequently employed to improve patient flow within ICUs, while healthcare professional-level strategies to enhance communication were less commonly used. While most studies improved ICU processes, only half succeeded in significantly reducing discharge delays and/or after-hours discharges, and only a third reported improved patient outcomes, highlighting the need for more effective interventions. IMPLICATIONS FOR CLINICAL PRACTICE: The findings of this review can guide the development of evidence-based, targeted, and tailored interventions aimed at improving patient and organisational outcomes.

Accuracy of intra-arterial line transducer levelling practice in a general intensive care unit.

BACKGROUND: The intra-arterial line is a common device intervention used in the intensive care environment to provide continuous blood pressure measurement. The transducer line is levelled to the patient's phlebostatic axis to provide accurate measurements. AIM: The aim of this study was to investigate registered nurses' accuracy at levelling the transducer to the correct anatomical position using visual judgement, compared to one done using a laser level. METHODS: Patient transducers were levelled by visual judgement and then by using a laser level. Time and mean arterial pressure (MAP) were recorded with each measurement along with any difference in transducer level between the two methods and subsequent changes in inotrope administration. RESULTS: A total of 577 MAP measurements were recorded from 178 patients; 70% of observations had a difference in transducer level, 30% of the time the inotrope rate was increased and 18% of the time the inotrope rate was reduced. The prevalence of clinically significant observations with an absolute difference of 50 mm or more in transducer placement was 25%. The mean difference in MAP measurements when a cut-off of 64 mmHg or more for laser was applied to the data was 0.22 (95% confidence interval: -0.14, 0.58, n = 513, p = 0.23), and for a cut-off of less than 64 for laser, a larger mean difference of 4.36 (95% confidence interval: 3.75, 5.28], n = 64, p < 0.001) was observed. CONCLUSIONS: Transducers were unable to be accurately levelled for haemodynamic monitoring using visual means alone. Over the range of patient MAP values examined, 25% of all observations had a clinically significant absolute difference of 50 mm or more in the transducer level position between the two methods. The visual method became increasingly inaccurate and unreliable at low MAP levels requiring medical intervention.

IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion-pellicle contact sites in Toxoplasma gondii.

The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitochondrion membrane and the parasite pellicle. The outer mitochondrial membrane-associated protein LMF1 is critical for the correct positioning of the mitochondrion. Intracellular parasites lacking LMF1 fail to form the lasso-shaped mitochondrion. To identify other proteins that tether the mitochondrion of the parasite to the pellicle, we performed a yeast two-hybrid screen for LMF1 interactors. We identified 70 putative interactors localized in different cellular compartments, such as the apical end of the parasite, mitochondrial membrane and the inner membrane complex (IMC), including with the pellicle protein IMC10. Using protein-protein interaction assays, we confirmed the interaction of LMF1 with IMC10. Conditional knockdown of IMC10 does not affect parasite viability but severely affects mitochondrial morphology in intracellular parasites and mitochondrial distribution to the daughter cells during division. In effect, IMC10 knockdown phenocopies disruption of LMF1, suggesting that these two proteins define a novel membrane tether between the mitochondrion and the IMC in Toxoplasma. This article has an associated First Person interview with the first author of the paper.

Prone positioning in patients with acute respiratory distress syndrome, translating research and implementing practice change from bench to bedside in the era of coronavirus disease 2019.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a relatively common condition of varied aetiology associated with high morbidity and mortality. A range of therapies have been proven to be useful for patients with ARDS, including ventilatory and nonventilatory strategies. Prone positioning is one of the nonventilatory strategies and has been proven to be safe and is associated with significant mortality benefit in patients with moderate to severe ARDS. It is now included in several international guidelines as the standard of care for these cases. OBJECTIVES: The aim of the study was to develop, implement, and evaluate a prone positioning program in two nonmetropolitan, nontertiary intensive care units in South East Queensland. METHODS: A Plan-Do-Study-Act quality improvement model was used to implement changes in clinical practice in relation to prone positioning of patients. RESULTS: A description of the methods used to promote a complex change strategy is provided in this article. CONCLUSIONS: In this article, we demonstrate the feasibility of introducing a nonventilatory intervention of prone positioning in the management of patients with moderate to severe ARDS in regional intensive care in South East Queensland. This implementation strategy could be replicated and adopted in other similar intensive care units that do not have the ability to provide tertiary services such as extracorporeal life support.

Identification of Fis1 Interactors in Toxoplasma gondii Reveals a Novel Protein Required for Peripheral Distribution of the Mitochondrion.

Toxoplasma gondii's single mitochondrion is very dynamic and undergoes morphological changes throughout the parasite's life cycle. During parasite division, the mitochondrion elongates, enters the daughter cells just prior to cytokinesis, and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular environment to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane and that this effect depends on the function of the fission-related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant-negative effect that affects the morphology of the mitochondrion. As this suggests that Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner, we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1, the mitochondrion is retracted away from the pellicle and instead is collapsed, as normally seen only in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth, and proper mitochondrial morphology is a prerequisite for mitochondrial division.IMPORTANCEToxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and congenitally infected. Current therapies are not effective against all life stages of the parasite, and many cause toxic effects. The single mitochondrion of this parasite is a validated drug target, and it changes its shape throughout its life cycle. When the parasite is inside a cell, the mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood and the proteins involved are currently not known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.

Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality.

A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor nuclear matrix protein 4 (Nmp4, Zfp384, Ciz, ZNF384) respond to several classes of osteoporosis drugs with enhanced bone formation compared with wild-type (WT) animals. Nmp4-/- mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyperanabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and Nmp4-/- MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production. We determined that Nmp4 has a broad impact on the transcriptome during osteogenic differentiation, contributing to the expression of over 5,000 genes. Phenotypic anchoring of transcriptional data was performed for the hypothesis-testing arm through analysis of cell metabolism, protein synthesis and secretion, and bone material properties. Mechanistic studies confirmed that Nmp4-/- MSPCs exhibited an enhanced capacity for glycolytic conversion: a key step in bone anabolism. Nmp4-/- cells showed elevated collagen translation and secretion. The expression of matrix genes that contribute to bone material-level mechanical properties was elevated in Nmp4-/- cells, an observation that was supported by biomechanical testing of bone samples from Nmp4-/- and WT mice. We conclude that loss of Nmp4 increases the magnitude of glycolysis upon the metabolic switch, which fuels the conversion of the osteoblast into a super-secretor of matrix resulting in more bone with improvements in intrinsic quality.

TgDrpC, an atypical dynamin-related protein in Toxoplasma gondii, is associated with vesicular transport factors and parasite division.

Dynamin-related proteins (Drps) are involved in diverse processes such as organelle division and vesicle trafficking. The intracellular parasite Toxoplasma gondii possesses three distinct Drps. TgDrpC, whose function remains unresolved, is unusual in that it lacks a conserved GTPase Effector Domain, which is typically required for function. Here, we show that TgDrpC localizes to cytoplasmic puncta; however, in dividing parasites, TgDrpC redistributes to the growing edge of the daughter cells. By conditional knockdown, we determined that loss of TgDrpC stalls division and leads to rapid deterioration of multiple organelles and the IMC. We also show that TgDrpC interacts with proteins that exhibit homology to those involved in vesicle transport, including members of the adaptor complex 2. Two of these proteins, a homolog of the adaptor protein 2 (AP-2) complex subunit alpha-1 and a homolog of the ezrin-radixin-moesin (ERM) family proteins, localize to puncta and associate with the daughter cells. Consistent with the association with vesicle transport proteins, re-distribution of TgDrpC to the IMC during division is dependent on post-Golgi trafficking. Together, these results support that TgDrpC contributes to vesicle trafficking and is critical for stability of parasite organelles and division.