Minerva Elements Records

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http://hdl.handle.net/11343/251382

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Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: a systematic review and meta-analysis.

Elias, KM ; Khan, SR ; Stadler, E ; Schlub, TE ; Cromer, D ; Polizzotto, MN ; Kent, SJ ; Turner, T ; Davenport, MP ; Khoury, DS (Elsevier BV, 2024-05)

BACKGROUND: Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, and medRxiv from database inception to Aug 16, 2023, for randomised placebo-controlled trials that tested virus-directed treatments (ie, any monoclonal antibodies, convalescent plasma, or antivirals) in non-hospitalised individuals with COVID-19. We only included studies that reported both clinical outcomes (ie, rate of disease progression to hospitalisation or death) and virological outcomes (ie, viral load within the first 7 days of treatment). We extracted summary data from eligible reports, with discrepancies resolved through discussion. We used an established meta-regression model with random effects to assess the association between clinical efficacy and virological treatment effect, and calculated I2 to quantify residual study heterogeneity. FINDINGS: We identified 1718 unique studies, of which 22 (with a total of 16 684 participants) met the inclusion criteria, and were in primarily unvaccinated individuals. Risk of bias was assessed as low in 19 of 22 studies for clinical outcomes, whereas for virological outcomes, a high risk of bias was assessed in 11 studies, some risk in ten studies, and a low risk in one study. The unadjusted relative risk of disease progression for each extra log10 copies per mL reduction in viral load in treated compared with placebo groups was 0·12 (95% CI 0·04-0·34; p<0·0001) on day 3, 0·20 (0·08-0·50; p=0·0006) on day 5, and 0·53 (0·30-0·94; p=0·030) on day 7. The residual heterogeneity in our meta-regression was estimated as low (I2=0% [0-53] on day 3, 0% [0-71] on day 5, and 0% [0-43] on day 7). INTERPRETATION: Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a potential surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. FUNDING: Australian Government Department of Health, Medical Research Future Fund, and Australian National Health and Medical Research Council.
The effect of informal caring on mental health among adolescents and young adults in Australia: a population-based longitudinal study

Alfonzo, LF ; Disney, G ; Singh, A ; Simons, K ; King, T (ELSEVIER SCI LTD, 2024-01)

BACKGROUND: Young carers are people aged up to 25 years who provide unpaid care to a relative or a friend living with a long-term condition or a disability. Providing informal care is associated with poor mental health. Longitudinal evidence on this relationship among young people is scarce. To address this gap, we assessed the mental health of people aged 15-25 years when providing informal care compared with when not providing informal care. METHODS: We conducted a population-based longitudinal study using 20 years of data between 2001 and 2020 from the Household Income and Labour Dynamics in Australia (HILDA) survey. We included observations of participants aged 15-25 years with at least two observations across 20 waves of HILDA. Informal care was categorised as 0 h per week, 1-19 h per week, and 20 or more h per week. Mental health was measured using the Mental Health Inventory (MHI-5) from the 36-Item Short Form Survey (SF-36). Multivariate linear fixed-effects regression models were fitted to assess within-person changes in mental health when providing different levels of informal care. FINDINGS: Of 44 663 people with 410 658 observations who participated in HILDA waves 1 to 20, 32 726 were excluded with 351 445 observations. 11 937 young people (with 59 213 observations) were deemed eligible for this study and, of these, 8996 participants with 43 231 observations were included in the complete case analytical sample. When caring for 1-19 h per week, young carers had an MHI-5 score of -1·98 points (95% CI -3·06 to -0·89) compared with when caring for 0 h per week. Mental health was worse when caring for 20 or more h per week, with participants displaying an MHI-5 score of -3·47 points (95% CI -6·02 to -0·92) compared with when caring for 0 h per week. Our findings were consistent across sensitivity tests. INTERPRETATION: Our findings suggest potential mental health effects of informal care in young people, particularly when providing an intense amount of caregiving. Reducing young caring loads could be a possible avenue for intervention. FUNDING: Melbourne Disability Institute Scholarship, University of Melbourne Research Training Program Scholarship, Australian Research Council Discovery Early Career Researcher Award, National Health and Medical Research Council of Australia funded Centre of Research Excellence in Disability and Health.
Inclusive mainstream services for people with intellectual disabilities: A relational approach

Wiesel, I ; Bigby, C ; van Holstein, E ; Gleeson, B (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2024-01-01)
Non-communicable disease mortality in young people with a history of contact with the youth justice system in Queensland, Australia: a retrospective, population-based cohort study

Calais-Ferreira, L ; Young, JT ; Francis, K ; Willoughby, M ; Pearce, L ; Clough, A ; Spittal, MJ ; Brown, A ; Borschmann, R ; Sawyer, SM ; Patton, GC ; Kinner, SA (ELSEVIER SCI LTD, 2023-08)

BACKGROUND: Young people who have had contact with the criminal justice system are at increased risk of early death, especially from injuries. However, deaths due to non-communicable diseases (NCDs) in this population remain poorly described. We aimed to estimate mortality due to NCDs in people with a history of involvement with the youth justice system, compare NCD mortality rates in this population with those in the general population, and characterise demographic and justice-related factors associated with deaths caused by NCDs in people with a history of contact with the youth justice system. METHODS: In this retrospective, population-based cohort study (the Youth Justice Mortality [YJ-Mort] study), we included all people aged 10-18 years (at baseline) charged with a criminal offence in Queensland, Australia, between June 30, 1993, and July 1, 2014. We probabilistically linked youth justice records with adult correctional records and national death records up to Jan 31, 2017. Indigenous status was ascertained from youth justice and adult correctional records, with individuals identified as Indigenous in either source classified as Indigenous in the final dataset. We estimated crude mortality rates and standardised mortality ratios (SMRs) for comparisons with data from the Australian general population. We identified risk factors for NCD deaths using competing-risks regression. FINDINGS: Of 48 670 individuals aged 10-18 years (at baseline) charged with a criminal offence in Queensland, Australia, between June 30, 1993, and July 1, 2014, 11 897 (24·4%) individuals were female, 36 773 (75·6%) were male, and 13 250 (27·2%) were identified as identified as Indigenous. The median age at first contact with the youth justice system was 15 years (IQR 14-16), the median follow-up time was 13·4 years (8·4-18·4), and the median age at the end of the study was 28·6 years (23·6-33·6). Of 1431 deaths, 932 (65·1%) had a known and attributed cause, and 121 (13·0%) of these were caused by an NCD. The crude mortality rate from NCDs was 18·5 (95% CI 15·5-22·1) per 100 000 person-years among individuals with a history of involvement with the youth justice system, which was higher than among the age-matched and sex-matched Australian general population (SMR 1·67 [1·39-1·99]). Two or more admissions to adult custody (compared with none; adjusted sub-distribution hazard ratio 2·09 [1·36-3·22]), and up to 52 weeks in adult custody (compared with none; 1·98 [1·18-3·32]) was associated with NCD death. INTERPRETATION: Young people with a history of contact with the justice system are at increased risk of death from NCDs compared with age-matched and sex-matched peers in the general Australian population. Reducing youth incarceration and providing young people's rights to access clinical, preventive, and restorative services should be a priority. FUNDING: National Health and Medical Research Council.
Lost in translation: a narrative review and synthesis of the published international literature on mental health research and translation priorities (2011-2023)

Palmer, VJ ; Wheeler, AJ ; Jazayeri, D ; Gulliver, A ; Hegarty, K ; Moorhouse, J ; Orcher, P ; Banfield, M (TAYLOR & FRANCIS INC, 2024-03-27)

BACKGROUND: Priority setting in mental health research is arguably lost in translation. Decades of effort has led to persistent repetition in what the research priorities of people with lived-experience of mental ill-health are. AIM: This was a narrative review and synthesis of published literature reporting mental health research priorities (2011-2023). METHODS: A narrative framework was established with the questions: (1) who has been involved in priority setting? With whom have priorities been set? Which priorities have been established and for whom? What progress has been made? And, whose priorities are being progressed? RESULTS: Seven papers were identified. Two were Australian, one Welsh, one English, one was from Chile and another Brazilian and one reported on a European exercise across 28 countries (ROAMER). Hundreds of priorities were listed in all exercises. Prioritisation mostly occured from survey rankings and/or workshops (using dots, or post-it note voting). Most were dominated by clinicians, academics and government rather than people with lived-experience of mental ill-health and carer, family and kinship group members. CONCLUSION: One lived-experience research led survey was identified. Few studies reported lived-experience design and development involvement. Five of the seven papers reported responses, but no further progress on priorities being met was reported.
Colonial Hero: Son Kijong in Narratives of Popular and National Korean History

Glade, J (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2024-04-02)
Implications of the UN Common Agenda for Australia: Renewing Multilateralism

Feller Ao, E ; Langmore Am, J (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2023-01-02)
Measuring housing well-being of disaster affected persons in Chennai (India)

Tiwari, P ; Shukla, J (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2023-01-01)
BECLIN1 is essential for intestinal homeostasis involving autophagy-independent mechanisms through its function in endocytic trafficking

Tran, S ; Juliani, J ; Harris, TJ ; Evangelista, M ; Ratcliffe, J ; Ellis, SL ; Baloyan, D ; Reehorst, CM ; Nightingale, R ; Luk, IY ; Jenkins, LJ ; Ghilas, S ; Yakou, MH ; Inguanti, C ; Johnson, C ; Buchert, M ; Lee, JC ; De Cruz, P ; Duszyc, K ; Gleeson, PA ; Kile, BT ; Mielke, LA ; Yap, AS ; Mariadason, JM ; Douglas Fairlie, W ; Lee, EF (NATURE PORTFOLIO, 2024-02-20)

Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show intestinal epithelium-specific BECLIN1 deletion in adult mice leads to rapid fatal enteritis with compromised gut barrier integrity, highlighting its intrinsic critical role in gut maintenance. BECLIN1-deficient intestinal epithelial cells exhibit extensive apoptosis, impaired autophagy, and stressed endoplasmic reticulum and mitochondria. Remaining absorptive enterocytes and secretory cells display morphological abnormalities. Deletion of the autophagy regulator, ATG7, fails to elicit similar effects, suggesting additional novel autophagy-independent functions of BECLIN1 distinct from ATG7. Indeed, organoids derived from BECLIN1 KO mice show E-CADHERIN mislocalisation associated with abnormalities in the endocytic trafficking pathway. This provides a mechanism linking endocytic trafficking mediated by BECLIN1 and loss of intestinal barrier integrity. Our findings establish an indispensable role of BECLIN1 in maintaining mammalian intestinal homeostasis and uncover its involvement in endocytic trafficking in this process. Hence, this study has important implications for our understanding of intestinal pathophysiology.
Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections

Cao, P ; Kho, S ; Grigg, MJ ; Barber, BE ; Piera, KA ; William, T ; Poespoprodjo, JR ; Jang, IK ; Simpson, JA ; Mccaw, JM ; Anstey, NM ; Mccarthy, JS ; Britton, S (NATURE PORTFOLIO, 2024-03-22)

Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated key biological parameters characterising in vivo PvLDH dynamics based on longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans, with the estimates informed by the ex vivo data as prior knowledge in a Bayesian hierarchical framework. We found that the in vivo accumulation rate of intraerythrocytic PvLDH peaks at 10-20 h post-invasion (late ring stage) with a median estimate of intraerythrocytic PvLDH mass at the end of the life cycle to be 9.4 × 10-3ng. We also found that the median estimate of in vivo PvLDH half-life was approximately 21.9 h. Our findings provide a foundation with which to advance our quantitative understanding of P. vivax biology and will facilitate the improvement of PvLDH-based diagnostic tools.

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