Publications by authors named "Samuel Dickson"

Article Synopsis
  • A study called ACTION-Galactosemia Kids evaluated the effects of govorestat, a drug for Classic Galactosemia, on children aged 2-17 by comparing it to a placebo over 18 months.
  • Govorestat showed a significant and lasting reduction in plasma galactitol levels, leading to stabilization or improvement in various clinical measures like behavior and daily living skills, while the placebo group showed decline.
  • Despite its benefits, govorestat did not show improvements in speech or gross motor skills, and both the drug and placebo groups experienced similar rates of adverse effects, indicating it is safe and well tolerated.
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Introduction: The reliable assessment of treatment outcomes for disease-modifying therapies (DMT) in neurodegenerative disease is challenging. The objective of this paper is to describe a generalized framework for developing composite scales that can be applied in diverse, degenerative conditions, termed "GENCOMS." Composite scales optimize the sensitivity for detecting clinically meaningful effects that slow disease progression.

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Calabash chalk (CaC) is an aluminium silicate hydroxide compound with heavy metal constituents, making it a potential neurotoxicant. Pregnant women often consume CaC as an antiemetic, which may interfere with the normal development of the foetal brain. Here, we evaluated the effects of CaC administration in pregnant rats on the brain of the offspring.

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Accurately defining gross tumour volume (GTV) and organs at risk (OAR) is key to successful radiation therapy (RT) treatment outcomes for patients with gynaecological cancers. With improved access to magnetic resonance imaging (MRI) for RT simulation and planning, the optimisation and tailoring of proven diagnostic MRI techniques towards RT specific planning goals is fast evolving. Modifying MRI techniques for radiation oncology (RO) with the priority of anatomy visualisation and spatial location over diagnosis and disease characterisation relies heavily on successful collaboration between radiology and radiation oncology staff.

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Background: Anti-amyloid vaccines may offer a convenient, affordable, and accessible means of preventing and treating Alzheimer's disease. UB-311 is an anti-amyloid-β active immunotherapeutic vaccine shown to be well-tolerated and to have a durable antibody response in a phase 1 trial. This phase 2a study assessed the safety, immunogenicity, and preliminary efficacy of UB-311 in participants with mild Alzheimer's disease.

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Key points of disagreement between the aducanumab FDA statistical review, which had primarily negative conclusions, and the clinical review, which had primarily positive conclusions, were investigated. Results from secondary endpoints in positive Study 302 were significant and these endpoints provided meaningful additional information. Findings indicate the statistical review of the aducanumab data was incorrect in a number of key areas.

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Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches.

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Article Synopsis
  • The Integrated Alzheimer's Disease Rating Scale (iADRS) is a comprehensive tool used to measure the severity of Alzheimer's disease by integrating cognitive and functional abilities into a single score, allowing for better interpretation of clinical findings from studies like TRAILBLAZER-ALZ.
  • Recent findings from the TRAILBLAZER-ALZ study showed that the Alzheimer's treatment donanemab effectively slowed disease progression by 32% over 18 months, making the iADRS a vital measure in evaluating the impact of disease-modifying therapies (DMTs).
  • Overall, the iADRS is a reliable assessment method in clinical trials for early symptomatic Alzheimer's patients, as it can accurately reflect clinical changes and treatment effects.
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Article Synopsis
  • Neisseria gonorrhoeae poses a significant public health risk due to rising cases and antimicrobial resistance, with whole-genome sequencing (WGS) evaluated for predicting susceptibility to various antimicrobials.
  • 481 isolates from five countries were analyzed, revealing that susceptibility to ciprofloxacin is linked to a specific genetic marker (gyrA codon 91), while predicting susceptibility to other drugs requires a multilocus approach.
  • All isolates tested were susceptible to zolifodacin, and while a single marker can guide ciprofloxacin treatment, a combination of markers is necessary for other medications.
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  • Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) has been shown to extend survival and slow decline in amyotrophic lateral sclerosis (ALS) patients.
  • The CENTAUR trial aimed to assess whether PB/TURSO improved survival without the need for tracheostomy or ventilation and reduced the occurrence of first hospitalizations.
  • Results indicated that patients treated with PB/TURSO had a 47% lower risk of key health events like death or needing ventilation compared to those on placebo, highlighting its potential benefits for ALS management.
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Introduction/aims: Trials incorporating placebo-to-active treatment crossover are encouraged in fatal conditions like amyotrophic lateral sclerosis (ALS) but may underestimate active treatment survival benefit. Here, we apply methods for modeling survival without crossover, including the rank-preserving structural failure time model (RPSFTM), to data from the CENTAUR trial of sodium phenylbutyrate and taurursodiol (PB and TURSO) in ALS incorporating both randomized placebo-controlled and open-label extension (OLE) phases.

Methods: Intent-to-treat (ITT) and RPSFTM survival analyses were performed with final data at a July 2020 cutoff date.

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Introduction: Recent clinical trials are considering inclusion of more than just apolipoprotein E () ε4 genotype as a way of reducing variability in analysis of outcomes.

Methods: Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation.

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Qualification of a biomarker for use in a medical product development program requires a statistical strategy that aligns available evidence with the proposed context of use (COU), identifies any data gaps to be filled and plans any additional research required to support the qualification. Accumulating, interpreting and analyzing available data is outlined, step-by-step, illustrated by a qualified enrichment biomarker example and a safety biomarker in the process of qualification. The detailed steps aid requestors seeking qualification of biomarkers, allowing them to organize the available evidence and identify potential gaps.

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Article Synopsis
  • Drug development for Alzheimer’s and other neurodegenerative dementias has faced many trials that failed to demonstrate the effectiveness of new drugs.
  • Exploratory clinical trials, which are shorter and smaller than traditional trials, aim to assess drug effects and can help determine whether to continue or terminate a drug's development.
  • Organizations like the Alzheimer’s Drug Discovery Foundation are working to create guidelines that improve the design and efficiency of these exploratory trials, potentially leading to faster and more cost-effective drug development.
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An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo.

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Background: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.

Methods: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months.

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Aim: Since the introduction of shared electric scooters to Auckland in October 2018, there have been multiple reports of injuries. We aim to examine the pattern of injuries sustained while riding electric scooters in patients presenting to hospital.

Methods: We conducted a retrospective analysis of patients who presented to Auckland City Hospital Emergency Department (ED) between 15 October 2018 and 22 February 2019.

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Introduction: Multidomain intervention for Alzheimer's disease (AD) risk reduction is an emerging therapeutic paradigm.

Methods: Patients were prescribed individually tailored interventions (education/pharmacologic/nonpharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical AD was classified as Prevention.

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Background: Due to the ability of the 8-aminoquinolines (8AQs) to kill different stages of the malaria parasite, primaquine (PQ) and tafenoquine (TQ) are vital for causal prophylaxis and the eradication of erythrocytic Plasmodium sp. parasites. Recognizing the potential role of cytochrome (CYP) 450 2D6 in the metabolism and subsequent hepatic efficacy of 8-aminoquinolines, studies were designed to explore whether CYP2D-mediated metabolism was related to the ability of single-dose PQ and TQ to eliminate the asexual and sexual erythrocytic stages of Plasmodium berghei.

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Background: Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates.

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Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR) agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP) vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge.

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Although many methods are available to test sequence variants for association with complex diseases and traits, methods that specifically seek to identify causal variants are less developed. Here we develop and evaluate a Bayesian hierarchical regression method that incorporates prior information on the likelihood of variant causality through weighting of variant effects. By simulation studies using both simulated and real sequence variants, we compared a standard single variant test for analyzing variant-disease association with the proposed method using different weighting schemes.

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