Publications by authors named "Heffernan A"

Article Synopsis
  • Ventriculitis in critically ill neurocritical care patients increases the risk of complications and death, prompting a need for improved antibiotic dosing strategies.
  • The study aimed to create a population pharmacokinetic (PK) model for piperacillin-tazobactam (PTZ) by analyzing samples from neurosurgical patients to determine effective dosing for cerebrospinal fluid (CSF) treatment.
  • Results showed significant inter-individual variability in drug penetration into CSF, making it difficult to recommend optimal dosing regimens despite some patients achieving high plasma drug levels.
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It has been thirty years since the end of political apartheid in South Africa in 1994. Those decades have been marked by single-party dominance under the African National Congress (ANC), and the expansion of democratic rights and public goods like education, as well as neoliberal economic policies, growing inequality and, in recent years, corruption and maladministration scandals. On the heels of a historic election in May 2024, one which marked the end of the ANC's electoral dominance and was shaped, in part, by government mismanagement of the energy sector and extensive infrastructural decline, it is a timely moment to consider the history of South Africa's state and its relation to industries of extraction and energy production.

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Article Synopsis
  • - Delirium is an acute neurological syndrome affecting cognition, impacting over 20% of medical patients and 50% of critically ill individuals, leading to significant distress, morbidity, and socioeconomic costs, particularly in the aging population.
  • - The understanding of delirium's underlying mechanisms is limited, with a focus on neuronal dysfunction, but recent research highlights the role of glial cells—especially astrocytes, microglia, and oligodendrocytes—in its pathophysiology.
  • - This review discusses how astrocyte-related issues, like disrupted brain metabolism and blood-brain barrier dysfunction, contribute to delirium, while also addressing the challenges of studying these mechanisms and the potential of advanced neuroimaging techniques for further insights
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Objective: To determine the carbon savings potential of incorporating virtual care into surgical care pathways for pediatric patients with obstructive sleep apnea or otitis media with effusion.

Methods: Pediatric patients with obstructive sleep apnea or otitis media with effusion were not enrolled, instead, a modeling cohort study design was used. This study utilized the British Columbia healthcare system and geography to model emissions.

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Article Synopsis
  • Obstructive sleep apnoea (OSA) and metabolic syndrome (MetS) are closely linked, with obesity playing a significant role in the development of both conditions through various mechanisms.
  • OSA can lead to weight gain and has a reciprocal relationship with diabetes, exacerbating its effects on the body, particularly through issues like intermittent hypoxia and sleep fragmentation.
  • There’s a growing need for research into the pathways connecting MetS and OSA, especially as new medications emerge that target obesity to improve patient outcomes.
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Background: Invasive fungal disease (IFD) in the early post-allogeneic HSCT (alloHCT) period is associated with increased likelihood of catastrophic outcomes. The utility of oral modified release (MR) posaconazole tablets is limited by reduced drug absorption from gastrointestinal toxicity induced by cytotoxic chemotherapy, necessitating a switch to the IV posaconazole formulation.

Objectives: To describe the population pharmacokinetics of posaconazole for oral MR and IV formulations in alloHCT patients and determine dosing regimens likely to achieve therapeutic exposures.

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Design/participants: This was a multicentre retrospective cohort study of adult patients (≥18 years) presenting with a process associated International Classification of Diseases code (ICD-AM-10) pertaining to sepsis between January 2017 and July 2020 to rural Emergency Departments.

Main Outcome Measures: Our primary outcome was antibiotic appropriateness as defined by the Australian Therapeutic Guidelines (for antibiotic selection relative to infecting source) and the National Antimicrobial Prescribing Survey tool. Our secondary outcome was in-hospital mortality.

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Background: Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient's baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8-20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels.

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The use of peak-picking algorithms is an essential step in all nontarget analysis (NTA) workflows. However, algorithm choice may influence reliability and reproducibility of results. Using a real-world data set, the aim of this study was to investigate how different peak-picking algorithms influence NTA results when exploring temporal and/or spatial trends.

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Non-target analysis (NTA) using high-resolution mass spectrometry is becoming a useful approach to screen for suspect and unknown chemicals. For comprehensive analyses, data-independent acquisition (DIA), like Sequential Windowed Acquisition of all THeoretical Mass Spectra (SWATH-MS) on Sciex instruments, is necessary, usually followed by library matching for feature annotation. The choice of parameters, such as acquisition window number and size, may influence the comprehensiveness of the suspect features detected.

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Research on per- and polyfluoroalkyl substances (PFAS) frequently incorporates organofluorine measurements, particularly because they could support a class-based approach to regulation. However, standardized methods for organofluorine analysis in a broad suite of matrices are currently unavailable, including a method for extractable organofluorine (EOF) measured using combustion ion chromatography (CIC). Here, we report the results of an international interlaboratory comparison.

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Objective: The aim was to discuss the role of non-type 2 inflammation in patients diagnosed with chronic rhinosinusitis (CRS) and comorbid lower airway disease.

Data Sources: Medline, Embase, National Institute for Health and Care Excellence, TRIP Database, ProQuest, Clinicaltrials.gov, Cochrane Central Registry of Controlled Trials, Web of Science, government and health organizations, and graduate-level theses.

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Background: Few large studies have investigated quality of life (QOL) for adults diagnosed with lower grade glioma (LGG).

Methods: QOL was assessed for 320 adults with LGG (World Health Organization grade 2/3) enrolled in the International Low Grade Glioma Registry by using the Medical Outcomes Study 36-Item Short Form health survey. Data on symptoms were also collected.

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Multilayer plastic pouch (MLPP) has an estimated 9% annual increase of market growth. However, the migrants it can introduce to food has not yet been systematically studied. A total of 79 MLPPs for baby food were purchased from major retail outlets in Australia.

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Objectives: To evaluate spasmodic dysphonia patients' perception of pain associated with laryngeal botulinum toxin (BTX) injections and to determine factors associated with higher pain scores relative to other included patients.

Methods: Prospective cohort study. Adult patients with adductor spasmodic dysphonia that presented to a tertiary laryngology practice for BTX injections were recruited from March to July 2022.

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Purpose: We aimed to identify a gene signature that discriminates between sepsis and aseptic inflammation in patients administered antibiotics in the intensive care unit and compare it to commonly utilised sepsis biomarkers.

Methods: 91 patients commenced on antibiotics were retrospectively diagnosed as having: (i) blood culture positive sepsis; (ii) blood culture negative sepsis; or (iii) aseptic inflammation. Bloods were collected after <24 h of antibiotic commencement for both gene expression sequencing analysis and measurement of previously identified biomarkers.

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Article Synopsis
  • - Plastics, made from organic polymers, are everywhere in daily life, especially in healthcare, but their breakdown into microplastics raises concerns about health impacts like inflammation and oxidative stress.
  • - There's limited research on microplastics affecting the eyes, but findings from other organs suggest potential risks to ocular health.
  • - Public concern over plastic waste has led to new laws aimed at reducing microplastics, and this review discusses their sources, effects on the eye, and the implications of current regulations.
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Treatment of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (alloHCT) patients with ganciclovir is complicated by toxicity and resistance. This study aimed to develop an intravenous ganciclovir population pharmacokinetic model for post-alloHCT patients and to determine dosing regimens likely to achieve suggested therapeutic exposure targets. We performed a prospective observational single-center pharmacokinetic study in adult alloHCT patients requiring treatment with intravenous ganciclovir for CMV viremia or disease.

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This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in kidney transplant patients. A population PK/PD model was developed with Monolix. Ganciclovir concentrations and CMV viral loads were obtained retrospectively from kidney transplant patients receiving routine clinical care.

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Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial.

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