11 research outputs found
Reassessing cognitive impairment prevalence in 5-FU chemotherapy: A critical methodological perspective
No full textLetter to EditorAlexandra L Whittaker, Ines Semendri
The effectiveness of anti-inflammatory agents in reducing chemotherapy-induced cognitive impairment in preclinical models – a systematic review
No full textPublished May 2023Chemotherapy-induced cognitive impairment (CICI) is a debilitating condition resulting from chemotherapy administration for cancer treatment. CICI is characterised by various cognitive impairments, including issues with learning, memory, and concentration, impacting quality of life. Several neural mechanisms are proposed to drive CICI, including inflammation, therefore, anti-inflammatory agents could ameliorate such impairments. Research is still in the preclinical stage; however, the efficacy of anti-inflammatories to reduce CICI in animal models is unknown. Therefore, a systematic review was conducted, with searches performed in PubMed, Scopus, Embase, PsycInfo and Cochrane Library. A total of 64 studies were included, and of the 50 agents identified, 41 (82%) reduced CICI. Interestingly, while nontraditional anti-inflammatory agents and natural compounds reduced impairment, the traditional agents were unsuccessful. Such results must be taken with caution due to the heterogeneity observed in terms of methods employed. Nevertheless, preliminary evidence suggests anti-inflammatory agents could be beneficial for treating CICI, although it may be critical to think beyond the use of traditional anti-inflammatories when considering which specific compounds to prioritise in development.Olivia J Haller, Ines Semendric, Rebecca P George, Lyndsey E Collins-Praino, Alexandra L Whittake
Neuroimmune reactivity marker expression in rodent models of chemotherapy-induced cognitive impairment: a systematic scoping review
No full textBackground: Chemotherapy-induced cognitive impairment (CICI) is a debilitating side effect arising from chemotherapy treatments. The condition is characterised by a range of cognitive deficits including impairment to memory, attention, and concentration. Whilst the underlying mechanisms that contribute to CICI remain unclear, neuroinflammation has been suggested as one key contributor. Method: A comprehensive systematic search of EMBASE and Medline via PubMed was conducted to identify studies on neuroimmune reactivity marker expression changes and resulting cognitive changes in preclinical rodent models of CICI. Results: A total of twenty studies met the eligibility criteria and were included in the scoping review. There was significant heterogeneity in the methodology employed in the included studies. Our findings demonstrate that widespread changes in cytokines, chemokines, microglia reactivity, and astrocyte reactivity are observed in CICI in the brain regions expected to be affected, given the nature of the cognitive impairment observed in CICI. Conclusions: Although there was considerable heterogeneity in study design that made comparisons between studies difficult, our findings suggest that neuroinflammation commonly occurs in CICI preclinical rodent models and shows an association with cognitive impairment.Rebecca P George, Ines Semendric, Mark R Hutchinson, Alexandra L Whittake
Reporting in rodent models of 'chemobrain': a systematic review assessing compliance with the ARRIVE guidelines
No full textPublished online: 2 June 2021Patients diagnosed with cancer are often plagued with debilitating side effects post-chemotherapy treatment. One such side effect is chemotherapy-induced cognitive impairment or ‘chemobrain’. Rodent models are commonly used to investigate pathogenesis and potential therapeutic strategies. However, concerns have been raised regarding inadequacies in reporting of animal studies rendering them unreliable and irreproducible. The aim of this systematic review was to assess compliance with the ARRIVE reporting guidelines in peer-reviewed publications evaluating chemotherapy-induced cognitive changes in rodent models, and to determine if the introduction of the ARRIVE guidelines has improved quality of reporting. A comprehensive search was conducted to identify relevant peer-reviewed publications. Ninety-seven studies met the eligibility criteria, and publication compliance with the ARRIVE guideline reporting was assessed. No studies achieved full adherence with the ARRIVE guidelines. Furthermore, no significant improvement was demonstrated in the overall compliance score post-ARRIVE. Given the lack of standardisation of animal models in this research area, these results pose particular threat to future progress and translation of findings in this area of research. These results highlight the need for stricter adherence to the ARRIVE guidelines by journal editors and reviewers. Animal Ethics Committees also have an important educative role in improving knowledge and awareness of the guidelines amongst researchers.Rebecca P. George, Ines Semendric, Eleanor R. Bowley-Schubert, Christine T. Chivonivoni, Alexandra P. Warrender, Alexandra L. Whittake
Changes in cognition and astrocytic reactivity in a female rodent model of chemotherapy-induced cognitive impairment are variable both acutely and chronically
No full textChemotherapy-induced cognitive impairment (CICI) affects female cancer survivors, with impairment recognised in populations such as breast cancer survivors, where 1 in 3 are affected. Impairments include issues with memory, learning, concentration, and processing speed, negatively impacting quality of life. Several mechanisms are proposed to drive these, with evidence implicating neuroinflammation as a key contributor. However, the time course over which impairments occur is less well-established, with fewer longer-term time-points investigated. This study aimed to understand the evolution of cognitive changes following methotrexate (MTX) or 5- fluorouracil (5-FU) chemotherapy, assessing three time-points: acute (96-hour), sub-acute (31-days) and chronic (93-days). Further, we investigated whether alterations in cognition were associated with concomitant changes in astrocytic reactivity. Female Sprague Dawley rats received two intraperitoneal injections of MTX, 5-FU or saline and were assessed on the novel object recognition, 5-choice serial reaction time task and Barnes maze. Hippocampal and prefrontal cortex tissue was examined for GFAP expression. Both MTX and 5-FU exposure were associated with spatial memory, task acquisition, and processing speed impairments at 31-days, with impairment ameliorated by 93-days. While both MTX and 5-FU induced changes in GFAP expression across various timepoints and regions, with most notable changes at 96-hours, 5-FU exhibited expression changes in the hippocampus consistently across all time-points. These results provide valuable insight into the complexity of a mediator of neuroinflammation in CICI. While neuroinflammation may be a promising therapeutic target, further markers should be assessed to elucidate the full neuroimmune response, and thus which aspects to target and when, to ensure optimal outcomes for cancer patients treated with chemotherapy.Olivia J. Haller, Ines Semendric, Lyndsey E. Collins-Praino, Alexandra L. Whittaker, Rebecca P. Georg
“Chemobrain” in childhood cancer survivors—the impact on social, academic, and daily living skills: a qualitative systematic review
No full textPublished online: 22 August 2023Purpose: To examine children’s experiences of chemotherapy-induced cognitive impairment––colloquially “chemobrain”–– and the impact on children’s social, academic, and daily living skills via a qualitative systematic review. Experiencing chemotherapy as a child, when the brain is still developing, may cause lifelong detriment to survivors’ lives. There is a significant gap in understanding their lived experience, including the self-identified barriers that children face following treatment. Such a gap can only be fully bridged by listening to the child’s own voice and/or parent proxy report through an exploration of the qualitative research literature. Methods: A search of MEDLINE, Embase, PsycINFO, and CINAHL databases was conducted. Inclusion criteria were qualitative studies with a focus on children (0–18 years) during and/or following chemotherapy treatment and explored children’s experiences of chemobrain. Results: Two synthesized findings were identified from six studies. (1) Chemobrain has an academic and psychosocial impact, which may not be understood by education providers. (2) Children and their parents have concerns about their reintegration and adaptation to school, social lives, and their future selves as independent members of society. Children’s experiences primarily related to changes in their academic and social functioning. Conclusion: This review highlights two important considerations: (1) the lived experiences of pediatric childhood cancer survivors guiding where future interventions should be targeted, and (2) a need to perform more qualitative research studies in this area, as well as to improve the quality of reporting among the existing literature, given that this is a current gap in the field.Ines Semendric, Danielle Pollock, Olivia J. Haller, Rebecca P. George, Lyndsey E. Collins-Praino, Alexandra L. Whittake
Mapping Evidence on Care Interventions for People Living With Motor Neurone Disease: A Protocol for a Living Evidence and Gap Map
No full textObjective To map the available evidence informing the care and management of people living with motor neurone disease (MND), including evidence pertaining to carers, asymptomatic genetic carriers, family, friends and healthcare professionals caring for people with MND. Introduction MND is a devasting neurodegenerative disease that has no cure and eventually leads to paralysis, progressive speech difficulties and respiratory failure. There are a plethora of interventions to support people living with MND, however, information regarding these interventions is often not organised in a manner that best supports the MND community. An evidence and gap map will provide a visual presentation that highlights the existing evidence that is available to support specific interventions, and indicate where there is no evidence. This will help inform future guideline and research efforts. Inclusion Criteria Studies if they describe care interventions for people living with MND, carers, asymptomatic genetic carriers, family, friends and healthcare professionals caring for people with MND. Peer-reviewed randomised controlled trials, and nonrandomised studies of interventions, systematic reviews and qualitative studies describing the experience of an intervention will be included. Methods An evidence and gap map will be conducted according to Campbell guidance and JBI guidance for scoping reviews. A comprehensive search of academic databases and clinical trial registries will be performed to identify eligible studies. An evidence inclusion framework has been developed with members of the MND community. Data screening and extraction will be independently performed by two reviewers. The evidence and gap map will be presented using EPPI Reviewer.Danielle Pollock, Cindy Stern, Melissa Bond, Timothy Hugh Barker, Sabira Hasanoff, Grace Holland, Ines Semendric, Anna Fragkoudi, Nipun Shrestha, Sebastian Cole Facchin-Young, Abigail Molly Day-Sharman, Lemma Negesa Bulto, Lara Stollery, Sitasma Sharma, Camille Schubert, Lynne Giles, Jay Beasley-Hall, Tracy Merlin, Julie Labra, Steve Vucic, Taryn Hunt, Zachary Mun
The Impact of Vegan Diets on Indicators of Health in Dogs and Cats: A Systematic Review
No full textThere has been an increase in vegetarianism and veganism in human populations. This trend also appears to be occurring in companion animals, with guardians preferring to feed their animals in accordance with their own dietary values and choices. However, there has been controversy amongst vets and online commentators about the safety of feeding vegan diets to carnivorous species, such as cats and dogs. In spite of this controversy, to date there has been no systematic evaluation of the evidence on this topic. A systematic search of Medline, Scopus, and Web of Science was performed, identifying 16 studies on the impact of vegan diets on cat and dog health. Studies were appraised for quality using established critical appraisal tools or reporting guidelines. There was considerable heterogeneity in the outcomes measured, and study designs employed, with few studies evaluating key outcomes of interest. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was utilized for assessment of certainty in the evidence, with the evidence for most outcomes being assessed as low or very low. Whilst the quality and amount of evidence needs to be considered in formulating recommendations, there was no overwhelming evidence of adverse effects arising from use of these diets and there was some evidence of benefits. It is, however, recommended that future high-quality studies, with standardized outcome measures and large sample sizes, be conducted. At the current time, if guardians wish to feed their companion animals vegan diets, a cautious approach should be taken using commercially produced diets which have been formulated considering the nutritional needs of the target species
Australian Motor Neurone Disease (MND) Guideline Project
No full textThe Australian MND Guideline Development Project aims to create evidence-based guidelines to improve the care and quality of life for people living with Motor Neurone Disease (MND).
This groundbreaking initiative will provide healthcare professionals, caregivers, and policymakers with actionable recommendations to enhance MND management across Australia.
This project is led by Health Evidence Synthesis, Recommendations, and Impact (HESRI) at the University of Adelaide, a global leader in evidence-based guideline development. Our team consists of experts in guideline methodology, evidence synthesis, health economics, biostatistics, lived experience research and engagement, ensuring a robust and inclusive approach to this important work.
FightMND is Australia’s leading organisation dedicated to finding effective treatments and a cure for Motor Neurone Disease. Through funding research, raising awareness, and advocating for people living with MND, FightMND is a vital partner in this project and the funder for this work
Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi studyResearch in context
No full textSummary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received
