Frailty as a trigger for goals-of-care discussions in rapid response calls: A single-centre retrospective cohort study.

BACKGROUND: Timely goals-of-care (GOC) discussions are essential for end-of-life planning, particularly during acute hospital admissions, where ambiguity often persists. Frailty, prevalent in the ageing population and linked to adverse outcomes, underscores the need to align treatment strategies with quality of life. Recognising frailty as a trigger for GOC discussions during rapid response calls (RRCs) is critical for efficient resource management and improving patient outcomes. METHODS: This single-centre retrospective cohort study included all hospitalised patients aged ≥65 years admitted between September 2021 and June 2023 who experienced an RRC. Frailty was assessed using the Clinical Frailty Scale (CFS) during the RRC. The primary outcome was to investigate whether frailty, specifically assessed by the CFS as screened during an RRC, could be a suitable clinical trigger for initiating GOC discussions. We also aimed to identify the proportion of patients with frailty (CFS score: ≥5) and predictors at the time of RRC, resulting in recommendations for GOC discussions. RESULTS: Among 4954 patients, 1685 (34.0%) were classified as frail (CFS score: ≥5). Recommendations increased with frailty levels (nonfrail [CFS score: 1-4]: 6.6%, mildly frail [CFS score: 5]: 19.3%, moderate-to-severely frail [CFS score: 6-9]: 32.2%; p < 0.001). Frailty independently increased the probability of GOC recommendations during an RRC (area under the receiver operating characteristic curve = 0.71). The CFS cut-off point for GOC recommendations was ≥5. The presence of frailty was associated with higher odds of receiving GOC recommendations for mildly frail (CFS score: 5; odds ratio [OR] = 2.53; 95% confidence interval: 1.96-3.27) and moderate-to-severely frail (CFS score: 6-9; OR = 4.69; 95% confidence interval: 3.81-5.78) compared to nonfrail patients. CONCLUSION: Frailty, identified during an RRC, served as a robust trigger for GOC recommendations, highlighting the importance of tailored proactive discussions before episodes of deterioration. Higher levels of frailty (CFS score: ≥5) demonstrate practical markers for aiding clinicians with proactive GOC discussions.

The limitations in implementing and operating a rapid response system.

Despite the widespread introduction of rapid response systems (RRS)/medical emergency teams (MET), there is still controversy regarding how effective they are. While there are some observational studies showing improved outcomes with RRS, there are no data from randomised controlled trials to support the effectiveness. Nevertheless, the MET system has become a standard of care in many healthcare organisations. In this review, we present an overview of the limitations in implementing and operating a RRS in modern healthcare.

Implementation and evaluation of a collaborative clinical pharmacist's medications reconciliation and charting service for admitted medical inpatients in a metropolitan hospital.

WHAT IS KNOWN AND OBJECTIVE: Medication errors on admission can persist throughout the episode of care and on to discharge leading to inappropriate management that can compromise patients' care. The aim of the study was to develop, implement and evaluate the role of pharmacist-led medication reconciliation and charting service for patients admitted to an Acute Assessment and Admission Unit via the Emergency Department in an electronic medication management environment at a metropolitan Australian hospital. METHODS: Following the credentialing of an experienced clinical pharmacist to perform collaborative medication charting, a prospective parallel study of medication errors was undertaken. Patients were randomly allocated to an intervention (n = 56) or a usual care (control) (n = 54) arm. Medication orders were charted by the medical staff in the usual care arm, whereas the pharmacist charted the medications in the intervention arm. An independent clinical pharmacist reviewed all the medication orders at 24 h after admission and errors recorded. The severity of errors was rated by a 'blinded' consultant physician and an independent senior pharmacist according to a standardized matrix. The potential time saving for the medical staff was investigated. A survey was conducted to assess the perception, acceptance and satisfaction of the service. RESULTS AND DISCUSSION: The intervention arm (reconciliation performed by pharmacist) achieved an error reduction greater than 80%. The average error rate decreased from 4·41 to 0·52 errors per patient (P < 0·0001) and 0·43-0·05 errors per order (P < 0·005). The severity of the errors was also diminished. Time evaluation estimated that the pharmacist can save more than 30 min per patient for the admitting medical officers. Staff satisfaction survey indicated that the service was well received by the medical staff. WHAT IS NEW AND CONCLUSION: A model of a collaborative clinical pharmacist reconciliation and charting service for admitted medical patients in an Australian hospital was successfully implemented. The service was well received and has shown to save medical staff time allowing them to attend to other duties. Moreover, the pharmacist charting and reconciliation service has resulted in a statistically significant reduction in medication errors.

A United Kingdom national survey of trends in ectopic pregnancy management.

Our national survey demonstrates increased use of medical and laparoscopic management of ectopic pregnancy in the UK. In the UK in 2000, 35% of cases were managed by laparoscopy, 63% by laparotomy and 1% with medication. A recent review in the USA revealed increasing rates of medical management and decreasing rates of laparotomy; a trend driven by both cost-effectiveness and patient choice. A total of 119 early pregnancy units were surveyed regarding the nature and management of the three most recent cases of ectopic pregnancy; in addition, feasibility of training residents was also requested. Participants reported on 124 cases with a median of five cases per month per department. A total of 57% of cases were managed laparoscopically, 31% medically, 5% by laparotomy and 6% conservatively. Out of 44 centres, 29 have the facilities for training in both intermediate laparoscopic surgery and early pregnancy ultrasound.

Interfacial edge dislocation interactions with free-surfaces in nanocrystals.

UNLABELLED: The configurational force experienced by a dislocation towards a free-surface is termed as the image force. In this work we consider a combination of two cases, wherein the image force experienced by an edge dislocation is considerably altered with respect to an edge dislocation in a semi-infinite body: (i) interfacial misfit edge dislocation in an epitaxial system and (ii) edge dislocation in a 2D nanocrystal. The interaction of an edge dislocation with a free-surface in a 2D nanocrystal can be: (i) attractive with a considerably altered magnitude and direction (as compared to the theoretically calculated value), (ii) neither attractive nor repulsive or (iii) even repulsive. To compute the image force on a misfit edge dislocation in a 2D nanocrystalline epitaxial system, a finite element model is constructed and stress-free strains are imposed in appropriate regions of the domain, to simulate an epitaxial system (Nb/Sapphire) and an interfacial dislocation. The results of the simulation are contrasted with the standard theoretical formulations, which are shown to be highly inadequate to handle such cases which involve epitaxial strains, two materials in the system and considerable domain deformations. KEYWORDS: Image Force, Finite Element Method, Interfacial Misfit Dislocation, Domain

Molecular ecology meets remote sensing: environmental drivers to population structure of humpback dolphins in the Western Indian Ocean.

Genetic analyses of population structure can be placed in explicit environmental contexts if appropriate environmental data are available. Here, we use high-coverage and high-resolution oceanographic and genetic sequence data to assess population structure patterns and their potential environmental influences for humpback dolphins in the Western Indian Ocean. We analyzed mitochondrial DNA data from 94 dolphins from the coasts of South Africa, Mozambique, Tanzania and Oman, employing frequency-based and maximum-likelihood algorithms to assess population structure and migration patterns. The genetic data were combined with 13 years of remote sensing oceanographic data of variables known to influence cetacean dispersal and population structure. Our analyses show strong and highly significant genetic structure between all putative populations, except for those in South Africa and Mozambique. Interestingly, the oceanographic data display marked environmental heterogeneity between all sampling areas and a degree of overlap between South Africa and Mozambique. Our combined analyses therefore suggest the occurrence of genetically isolated populations of humpback dolphins in areas that are environmentally distinct. This study highlights the utility of molecular tools in combination with high-resolution and high-coverage environmental data to address questions not only pertaining to genetic population structure, but also to relevant ecological processes in marine species.

Amazon River enhances diazotrophy and carbon sequestration in the tropical North Atlantic Ocean.

The fresh water discharged by large rivers such as the Amazon is transported hundreds to thousands of kilometers away from the coast by surface plumes. The nutrients delivered by these river plumes contribute to enhanced primary production in the ocean, and the sinking flux of this new production results in carbon sequestration. Here, we report that the Amazon River plume supports N(2) fixation far from the mouth and provides important pathways for sequestration of atmospheric CO(2) in the western tropical North Atlantic (WTNA). We calculate that the sinking of carbon fixed by diazotrophs in the plume sequesters 1.7 Tmol of C annually, in addition to the sequestration of 0.6 Tmol of C yr(-1) of the new production supported by NO(3) delivered by the river. These processes revise our current understanding that the tropical North Atlantic is a source of 2.5 Tmol of C to the atmosphere [Mikaloff-Fletcher SE, et al. (2007) Inverse estimates of the oceanic sources and sinks of natural CO(2) and the implied oceanic carbon transport. Global Biogeochem Cycles 21, doi:10.1029/2006GB002751]. The enhancement of N(2) fixation and consequent C sequestration by tropical rivers appears to be a global phenomenon that is likely to be influenced by anthropogenic activity and climate change.

Evaluation of the efficacy of transcricoid lignocaine as adjunctive local anaesthesia for fiberoptic bronchoscopy.

INTRODUCTION: Optimisation of patient comfort during flexible bronchoscopy is achieved with the use of intravenous sedation and vocal anaesthesia. METHODS: The effect of transcricoid lignocaine injection was investigated with regards to ease of procedure and frequency of cough. A single-blinded study was carried out and two visual analogue scales were used as markers of efficacy. Treatment groups were matched for age, gender and total dose of lignocaine administered. RESULTS: The results highlighted a significant improvement in the perceived ease of procedure (p < 0.0001) and frequency of coughing during the procedure (p < 0.0001). CONCLUSION: The findings of the study demonstrate that the use of transcricoid injection of lignocaine provided a safe adjunct for anaesthesia in flexible bronchoscopy.

Validation and method development of Tadalafil in bulk and tablet dosage form by RP-HPLC.

A novel, precise, rapid and sensitive reverse phase high performance liquid chromatographic method has been developed for the validated estimation of Tadalafil in bulk and tablet dosage form. The separation was achieved on Agilent Eclipse XDB C18 column (150 mm×4.6 mm, 5 µ) using a mobile phase that consists of the buffer (potassium dihydrogen orthophosphate) and acetonitrile in the ration of 50:50 V/V, pH 6 was adjusted with orthophosphoric acid. The flow rate was maintained at 1.2 ml/min and the detection wavelength was 285 nm. The method was validated for linearity, specificity, sensitivity as per ICH guidelines. The retention time was found to be 3.181 for Tadalafil. The calibration curve was linear over the concentration range of 10-150 µg/ml. The % RSD was satisfactory which showed the method found to be reliable. The high percentage recovery confirmed the suitability of the method for estimation of Tadalafil in pharmaceutical dosage form. The developed method could be applicable for routine analysis of Tadalafil in bulk and tablet dosage form.

A multipurpose vector for the study of transcriptional control.

To facilitate the insertion of transcriptional control regions next to a reporter gene, plasmid vectors containing multiple cloning sites next to the cat have been constructed. These vectors also contain features which make their use convenient for the construction of deletions in the inserted transcriptional control regions, as well as for the direct sequencing of the deletion series produced. The vectors have been constructed such that the control region cassette (and the deletions produced) may be easily removed with or without the reporter gene for placement into transgenic mice. The system's utility has been demonstrated by deletion analysis of a chicken myosin heavy chain-encoding gene promoter.

Strategies for optimal synthesis and secretion of heterologous proteins in the methylotrophic yeast Pichia pastoris.

Numerous heterologous proteins have been produced at greater than gram per liter levels in the methylotrophic yeast, Pichia pastoris, using the methanol oxidase promoter. The factors that drastically influence protein production in this system include: copy number of the expression cassette, site and mode of chromosomal integration of the expression cassette, mRNA 5'- and 3'-untranslated regions (UTR), translational start codon (AUG) context, A+T composition of cDNA, transcriptional and translational blocks, nature of secretion signal, endogenous protease activity, host strain physiology, media and growth conditions, and fermentation parameters. All these factors should be considered in designing an optimal production system. The inherent ability of P. pastoris to convert the zymogen (pro-enzyme) form of matrix metalloproteinases (MMP) into active mature forms (which tend to self-degrade, and in some instances also cause damage to cells), largely limits the use of this system for the production of MMP. However, this problem can be partly alleviated by co-expression of tissue inhibitor of MMP (TIMP-1).

Inhibition of interleukin 2 receptor expression in normal human T cells by cyclosporine. Demonstration at the mRNA, protein, and functional levels.

In view of the importance of the IL-2 receptors in the expression of antiallograft immunity and the currently existing controversy regarding the effect of CsA on the induction of IL-2 receptors, we explored the effect of cyclosporine on the induction of interleukin-2 receptor alpha and beta in normal human T cells. The effect of CsA on the induction of IL-2 receptors was examined at the levels of mRNA expression (with the aid of the polymerase chain reaction), protein (by SDS-PAGE analysis of chemically crosslinked 125I-IL-2 membrane protein complexes and by FACS), and function (by Scatchard analysis of 125I-IL-2 binding to T cells). The T cells were signaled with sn-1,2-dioctanoylglycerol and ionomycin or with crosslinked anti-CD3 and anti-CD2 mAbs. Our experimental design revealed that (A) CsA inhibits the induction of IL-2 receptor alpha and beta in normal human T cells, (B) the inhibitory activity is realized by a direct effect on T cells, and (C) the inhibitory activity is detectable at the pretranslational level--CsA significantly reduced the induction of mRNA encoding IL-2 receptor alpha and IL-2 receptor beta. These observations together persuasively demonstrate the ability of CsA to interrupt the emergence of IL-2 receptors on the surface of normal human T cells.

The molecular basis for the synergism between the CD3/alpha beta T cell receptor and the CD2 antigen-derived signals in promoting T-cell proliferation.

Northern blot analysis and a highly sensitive methodology for mRNA phenotyping, polymerase chain reaction (PCR), were used to explore the basis for the synergism between CD3/alpha beta T cell receptor (TCR) and the CD2 antigen-derived signals in promoting proliferation of T cells. Northern blotting of RNA isolated from highly purified normal human T cells revealed that crosslinking of anti-TCR-1 (a mAb directed at a framework determinant of the TCR) and OKT11 (a mAb directed at the SRBC-binding epitope of the CD2 antigen) induced the expression of the interleukin-2 gene and the gene for IL-2 receptor alpha, mRNA phenotyping by PCR revealed that crosslinkage of TCR with the CD2 antigen, and not independent crosslinking of TCR or the CD2 antigen, results in the induction of IL-2, IL-2 receptors alpha and beta, and IL-4-specific transcripts. Highly purified CD4+ T cells, as well as CD8+ T cells proliferated by crosslinking TCR with CD2 antigen. Moreover, crosslinkage of TCR with the CD2 antigen and not of either antigen with the CD4 antigen (on the surface of CD4+ T cells) or the CD8 antigen (on the surface of CD8+ T cells) resulted in marked proliferation. Our demonstration that the CD2 antigen-derived signal(s) contribute to the expression of growth promoting genes elicited via the TCR, and that the CD2 antigen is more efficient compared with the CD4 or CD8 antigen in evoking T cell proliferation, suggests that autoimmunity as well as alloimmunity might be regulated by targeting the CD2 antigen.

True hermaphroditism presenting as intermittent hematuria and groin pain.

True hermaphroditism was diagnosed when a male was evaluated for inguinal swelling and hematuria. A true hermaphrodite rarely has bilaterally descended gonads. This patient had intrascrotal ovotestes. Diagnosis and management of the true hermaphrodite are reviewed.

The occurrence of a furanoid fatty acid inHevea brasiliensis latex.

Methyl esters from the triglyceride fraction of the neutral lipids of natural rubber latex were found by gas liquid chromatography to contain about 90% of a furanoid acid. Spectroscopic analysis identified the acid as 10,13-epoxy-11-methyloctadeca-10,12-dienoic acid.

Vagino-cornual cannulation and embryo recovery from crossbred (Bos indicusxBos taurus) heifers.

Successful vaginal and bicornual cannulations were performed with a tabular cannulator shaped like a giant hypodermic needle in crossbred (Bos indicusxBos taurus) heifers (n=7). A total of 58 embryos from a possible 73 were flushed out. The embryo recovery rate was 79.45% and average recovery time was 50 minutes. The wound healing at cannulation sites was rapid. All heifers except one conceived due to insemination during subsequent cycles. One heifer developed pyometra and did not settle.