Publications by authors named "Coughlan K"

Background: Despite evidence supporting interventions that improve outcomes for patients with stroke, their implementation remains suboptimal. Facilitation can support implementation of research into clinical practice by helping people develop the strategies to implement change. However, variability in the amount (dose) and type of facilitation activities/facilitator roles that make up the facilitation strategies (content), may affect the effectiveness of facilitation.

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Background: The Quality in Acute Stroke Care (QASC) Trial demonstrated that assistance to implement protocols to manage Fever, hyperglycaemia (Sugar) and Swallowing (FeSS) post-stroke reduced death and disability. In 2017, a 'Strong Recommendation' for use of FeSS Protocols was included in the Australian Clinical Guidelines for Stroke Management. We aimed to: i) compare adherence to FeSS Protocols pre- and post-guideline inclusion; ii) determine if adherence varied with prior participation in a treatment arm of a FeSS Intervention study, or receiving treatment in a stroke unit; and compare findings with our previous studies.

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Article Synopsis
  • - The study evaluated the impact of nurse-led implementation of protocols to manage fever, hyperglycemia, and swallowing in German stroke units, showing significant improvements in adherence to these protocols after training and support from an Australian team.
  • - Results indicated a notable increase in overall adherence from 20% to 28%, with specific improvements in managing hyperglycemia (from 43% to 55%) and swallowing (from 52% to 61%), though fever protocol adherence showed little change.
  • - Additional findings revealed increased timely administration of anti-pyretics and insulin, as well as improved screening for swallowing within 24 hours of admission, highlighting the effectiveness of the implemented support strategies.
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Isolated methylmalonic acidemia/aciduria (MMA) due to MMUT enzyme deficiency is an ultra-rare pediatric disease with high morbidity and mortality, with no approved disease-altering therapies. Previous publications showed that systemic treatment with a codon-optimized mRNA encoding wild-type human MMUT (MMUT) is a promising strategy for treatment of MMA. We developed a second-generation drug product, mRNA-3705, comprised of an mRNA encoding the MMUT enzyme formulated in a lipid nanoparticle (LNP) with incorporation of enhancements over the previous clinical candidate mRNA-3704.

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Commercially produced cyanobacteria preparations sold under the name spirulina are widely consumed, due to their traditional use as a nutrient-rich foodstuff and subsequent marketing as a superfood. Despite their popularity, the microbial composition of ponds used to cultivate these bacteria is understudied. A total of 19 pond samples were obtained from small-scale spirulina farms and subjected to metagenome and/or virome sequencing, and the results were analysed.

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Messenger RNA (mRNA) therapeutics delivered via lipid nanoparticles hold the potential to treat metabolic diseases caused by protein deficiency, including propionic acidemia (PA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Herein we report results from multiple independent preclinical studies of mRNA-3927 (an investigational treatment for PA), mRNA-3705 (an investigational treatment for MMA), and mRNA-3210 (an investigational treatment for PKU) in murine models of each disease. All 3 mRNA therapeutics exhibited pharmacokinetic/pharmacodynamic (PK/PD) responses in their respective murine model by driving mRNA, protein, and/or protein activity responses, as well as by decreasing levels of the relevant biomarker(s) when compared to control-treated animals.

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Article Synopsis
  • The QASC Australia trial showed that nurse-led protocols for managing fever, sugar levels, and swallowing (FeSS Protocols) can reduce deaths and disabilities after a stroke, prompting a larger study in Europe involving 64 hospitals across 17 countries to evaluate the scalability of these protocols.
  • The implementation process was supported by a multi-stakeholder framework that included academic partners and the Angels Initiative, a non-profit organization focused on promoting evidence-based stroke care.
  • A qualitative evaluation was conducted through interviews with various stakeholders to identify factors affecting the engagement and implementation of the FeSS Protocols, revealing three main themes regarding the challenges and facilitators of this process.
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BACKGROUND: Stroke unit care reduces patient morbidity and mortality. The Quality in Acute Stroke Care Europe Study achieved significant large-scale translation of nurse-initiated protocols to manage Fever, hyperglycemia (Sugar), and Swallowing (FeSS) in 64 hospitals across 17 European countries. However, not all hospitals had stroke units.

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Traditional models of oxidative stress predict accumulation of damage caused by reactive oxygen species (ROS) production as highly correlated with aerobic metabolism, a prediction under increasing scrutiny. Here, we repeat sampled female great tits (Parus major) at two opposite levels of energy use during the period of maximum food provisioning to nestlings, once at rest and once during activity. Our results were in contrast to the above prediction, namely significantly higher levels of oxidative damage during rest opposed to active phase.

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Article Synopsis
  • The Registry of Stroke Care Quality (RES-Q) is an international platform that helps standardize the evaluation of stroke care quality and performance in hospitals.
  • A survey conducted between October 2021 and February 2022 reached out to local coordinators from 1463 hospitals globally, with 358 responses, revealing that RES-Q data is frequently utilized to enhance stroke care quality, track improvements, and benchmark practices.
  • A significant number of respondents expressed the need for formal training and education on using RES-Q data effectively, indicating that understanding quality improvement methods could lead to better clinical practices and outcomes in stroke care.
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Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid β-oxidation (FAO) in humans. Patients exhibit clinical episodes often associated with fasting. Symptoms include hypoketotic hypoglycemia and Reye-like episodes.

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Article Synopsis
  • - Poor adherence to stroke care guidelines is a global issue, but the QASC trial showed that nurse-led implementation can significantly improve patient outcomes like death and disability.
  • - A multi-country study from 2017 to 2021 assessed the effectiveness of the FeSS Protocol across 64 hospitals, revealing substantial improvements in the care elements related to fever, hyperglycemia, and swallowing.
  • - The successful rollout of the FeSS Protocol across diverse healthcare systems demonstrated that both high-income and middle-income countries could achieve similar enhancements in stroke care practices.
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Crigler-Najjar syndrome is a rare disorder of bilirubin metabolism caused by uridine diphosphate glucuronosyl transferase 1A1 () mutations characterized by hyperbilirubinemia and jaundice. No cure currently exists; treatment options are limited to phototherapy, whose effectiveness diminishes over time, and liver transplantation. Here, we evaluated the therapeutic potential of systemically administered, lipid nanoparticle-encapsulated human (h) mRNA therapy in a Crigler-Najjar mouse model.

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Background: Facilitated implementation of nurse-initiated protocols to manage fever, hyperglycaemia (sugar) and swallowing difficulties (FeSS Protocols) in 19 Australian stroke units resulted in reduced death and dependency for stroke patients. However, a significant gap remains in translating this evidence-based care bundle protocol into standard practice in Australia and New Zealand. Facilitation is a key component for increasing implementation.

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Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inborn error of long chain fatty acid β-oxidation (FAO) with limited treatment options. Patients present with heterogeneous clinical phenotypes affecting predominantly heart, liver, and skeletal muscle. While VLCAD deficiency is a systemic disease, restoration of liver FAO has the potential to improve symptoms more broadly due to increased total body ATP production and reduced accumulation of potentially toxic metabolites.

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Recent evidence indicates that activation of adenosine monophosphate-activated protein kinase (AMPK), a highly conserved sensor and modulator of cellular energy and redox, regulates cell mitosis. However, the underlying molecular mechanisms for AMPKα subunit regulation of chromosome segregation remain poorly understood. This study aimed to ascertain if AMPKα1 deletion contributes to chromosome missegregation by elevating Polo-like kinase 4 (PLK4) expression.

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Amyotrophic lateral sclerosis (ALS) presents a poorly understood pathogenesis. Evidence from patients and mutant SOD1 mouse models suggests vascular damage may precede or aggravate motor dysfunction in ALS. We have previously shown angiogenin (ANG) treatment enhances motor neuron survival, delays motor dysfunction and prevents vascular regression in the SOD1 ALS model.

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Citrin deficiency is an autosomal recessive disorder caused by loss-of-function mutations in SLC25A13, encoding the liver-specific mitochondrial aspartate/glutamate transporter. It has a broad spectrum of clinical phenotypes, including life-threatening neurological complications. Conventional protein replacement therapy is not an option for these patients because of drug delivery hurdles, and current gene therapy approaches (e.

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Loss-of-function mutations in the angiogenin (ANG) gene have been identified in familial and sporadic ALS patients. Previous work from our group identified human ANG (huANG) to protect motoneurons in vitro, and provided proof-of-concept that daily intraperitoneal (i.p.

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Background: Riluzole is the most widespread therapeutic for treatment of the progressive degenerative disease amyotrophic lateral sclerosis (ALS). Riluzole gained FDA approval in 1995 before the development of ALS mouse models. We assessed riluzole in three transgenic ALS mouse models: the SOD1 model, the TDP-43 model, and the recently developed FUS (1-359) model.

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AMP-activated protein kinase (AMPK) is an enzyme crucial in cellular metabolism found to be inhibited in many metabolic diseases including type 2 diabetes. Thiazolidinediones (TZDs) are a class of anti-diabetic drug known to activate AMPK through increased phosphorylation at Thr, however there has been no research to date on whether they have any effect on inhibition of AMPK's lesser known site of inhibition, Ser. HepG2 cells were treated with troglitazone and phosphorylation of AMPK was found to increase at both Thr and Ser in a dose- and time-dependent manner.

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Background And Purpose: Implementation of nurse-initiated protocols to manage fever, hyperglycemia, and swallowing dysfunction decreased death and disability 90 days poststroke in the QASC trial (Quality in Acute Stroke Care) conducted in 19 Australian acute stroke units (2005-2010). We now examine long-term all-cause mortality.

Methods: Mortality was ascertained using Australia's National Death Index.

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