Publications by authors named "Slee A"

Prescribing errors are a source of preventable harm in healthcare, which may be mitigated using Electronic Prescribing (EP) systems. Anyone who routinely prescribes medication could benefit from digitally assisted automated checks to identify whether a prescription should potentially not be allowed (e.g.

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Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis response can result in anxiety and other neuropsychiatric disorders and effective therapeutics are needed to mitigate this maladaptive response. Here we examined the effects of Teneurin C-terminal Associated Peptide (TCAP)-1, a peptide known to inhibit corticotropin releasing factor (CRF)-mediated stress, on the physiological expression of stress, and whether the effects of TCAP-1 were dependent on the route of administration. We first examined whether subcutaneous administration of TCAP-1 influenced tube restraint stress-induced corticosterone (CORT) increases in both male mice and rats.

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Background: Practice guidelines recommend ablation (ABL) in atrial fibrillation (AF) for rhythm control. Guidance for antiarrhythmic drugs (AADs) post-ABL is limited.

Objective: The purpose of this study was to determine AAD and ABL practices in the United States and Europe.

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Article Synopsis
  • - Antibiotic-resistant infections are a major global health concern, causing over 700,000 deaths annually, leading to the development of ePAMS+, an ePrescribing tool aimed at improving antibiotic usage and combating resistance in healthcare settings.
  • - A non-randomised trial was conducted in two English hospitals during the pandemic to assess the feasibility and usability of ePAMS+, involving interviews and quantitative data collection to evaluate its implementation and effects on antibiotic prescribing practices.
  • - Results from 60 interviews and nearly 2,000 patient admissions indicated some aspects of ePAMS+ were well-received, though improvements are needed for certain features, highlighting both the potential and challenges of adopting this antimicrobial stewardship tool in clinical settings.
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Article Synopsis
  • - Chronic kidney disease affects around 13% of the global population and is expected to be a major cause of life years lost by 2040, with end-stage kidney disease leading to complications like renal cachexia, which is not well understood and has limited treatment options.
  • - The study aims to understand the experiences of individuals with renal cachexia and their carers through in-depth interviews, adhering to ethical research practices in a UK healthcare setting.
  • - Seven participants (four patients and three carers) were recruited, with the data analyzed to identify six key themes related to their lived experiences, including issues like appetite loss, weight decline, social withdrawal, and emotional struggles.
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This study reveals that Fc-enhanced anti-CTLA-4 harnesses novel mechanisms to overcome the limitations of conventional anti-CTLA-4, effectively treating poorly immunogenic and treatment-refractory cancers. Our findings support the development of a new class of immuno-oncology agents, capable of extending clinical benefit to patients with cancers resistant to current immunotherapies.

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Background: Antimicrobial resistance (AMR) represents a growing concern for public health.

Objective: We sought to explore the challenges associated with development and implementation of a complex intervention designed to improve AMS in hospitals.

Methods: We conducted a qualitative evaluation of a complex AMS intervention with educational, behavioral, and technological components in 5 wards of an English hospital.

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Introduction: Minimally invasive radical hysterectomy (MIRH) has been reported to have a four-fold increase in recurrence compared to open radical hysterectomy (ORH) for the treatment of early-stage cervical cancer. The cause for the inferior outcomes with MIRH is unclear. However, the use of a uterine manipulator and the lack of tumor containment strategies may contribute to tumor seeding in previous MIRH approaches.

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Background & Aims: Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies. However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse. Cachexia and malnutrition are known secondary syndromes in many cancer patients, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterise these issues in CAR T-cell patients.

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Background: Pembrolizumab, an immune checkpoint inhibitor, indicated to treat multiple cancers, was initially approved in Australia as weight-based dosing at 2 mg/kg every 3 weeks (Q3W). Subsequent approvals used 'fixed' dosages of 200 mg Q3W or 400 mg every 6 weeks (Q6W). Pharmacokinetic equivalence was demonstrated between dosing strategies, with no significant differences in efficacy or toxicity.

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Rationale: Corticotropin-releasing factor (CRF), the apical stress-inducing hormone, exacerbates stress and addictive behaviors. TCAP-1 is a peptide that directly inhibits both CRF-mediated stress and addiction-related behaviors; however, the direct action of TCAP-1 on morphine withdrawal-associated behaviors has not previously been examined.

Objective: To determine whether TCAP-1 administration attenuates behavioral and physiological consequences of morphine withdrawal in mice.

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Specific pediatric populations have exhibited disparate responses to triiodothyronine (T3) repletion during and after cardiopulmonary bypass (CPB). Objective: To determine if T3 supplementation improves outcomes in children undergoing CPB. We searched randomized controlled trials (RCT) evaluating T3 supplementation in children aged 0-3 years undergoing CPB between 1/1/2000 and 1/31/2022.

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Purpose Of Review: Renal cachexia is a deleterious condition characterized by weight loss, muscle wasting and loss of physical function, quality of life, and increased mortality. Multimodal treatment strategies utilizing exercise and nutrition interventions have been recently suggested although the evidence base is still in its infancy. This paper aimed to review the current literature surrounding the use of exercise and nutrition for renal cachexia.

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Article Synopsis
  • The study aimed to determine if the duration of type 2 diabetes affects how canagliflozin influences cardiovascular and kidney outcomes.
  • An analysis was conducted on two major trials involving over 14,500 participants to assess the impact of canagliflozin on various outcomes related to heart and kidney health, particularly focusing on changes in albumin levels over different durations of diabetes.
  • Results indicated that canagliflozin consistently benefits cardiovascular and kidney health regardless of how long a person has had type 2 diabetes, suggesting that early treatment is advantageous.
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Background: This study evaluated the effects of canagliflozin in patients with type 2 diabetes with and without prevalent cardiovascular disease (secondary and primary prevention).

Methods And Results: This was a pooled participant-level analysis of the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. The CANVAS Program included participants with type 2 diabetes at elevated cardiovascular risk, whereas the CREDENCE trial included participants with type 2 diabetes and albuminuric chronic kidney disease.

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Background: Direct oral anticoagulants have the potential to improve care in children requiring chronic anticoagulation. Edoxaban has favourable pharmacokinetics that could benefit younger patients but data on long-term safety and efficacy for specific paediatric indications are lacking.

Study Aims: We present a single-centre experience using edoxaban in children who require chronic anticoagulation for large coronary artery aneurysms secondary to Kawasaki disease.

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Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) on patient-centred outcomes in patients with CC.

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Aim: In the CANVAS Program and CREDENCE trials, the sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of cardiovascular and kidney events in patients with type 2 diabetes. The current study analysed a pooled population to ascertain the kidney protection provided by canagliflozin across the full spectrum of kidney parameters.

Methods: This post-hoc pooled analysis of the CANVAS Program (N = 10 142) and CREDENCE trial (N = 4401), assessed the risk of the primary kidney composite (doubling of serum creatinine, end-stage kidney disease, renal death), in all patients and subgroups defined by baseline estimated glomerular filtration rate (<30, 30 to <45, 45 to <60 and ≥60 ml/min/1.

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Aims: Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity.

Methods And Results: We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities.

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Background: Antimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+).

Methods: ePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients.

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