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ItemViral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: a systematic review and meta-analysis.(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.
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ItemThe effect of informal caring on mental health among adolescents and young adults in Australia: a population-based longitudinal study(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.
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ItemInclusive mainstream services for people with intellectual disabilities: A relational approach(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2024-01-01)
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ItemPredictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy.(Elsevier BV, 2024-04)BACKGROUND: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. METHODS: In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. FINDINGS: 67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4 ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). INTERPRETATION: Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. FUNDING: This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.
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ItemNon-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(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.
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Item'If we take the engine out, how will the car go?': beliefs, understanding and access to vasectomy services in Timor-Leste.(Informa UK Limited, 2024-04-18)Vasectomy is a safe, highly effective and affordable method of permanent contraception, and one of the few currently available contraceptive methods for men. Despite this, vasectomy uptake remains overall low, making up just 2% of the global contraceptive method mix. To better understand access to vasectomy in a country with negligible uptake, we conducted participatory and operational research in the Democratic Republic of Timor-Leste (Timor-Leste). We held 14 participatory group discussions with 175 community participants (84 men, 91 women; aged 18-72) across seven municipalities (Ainaro, Baucau, Bobonaro, Dili, Lautem, Manufahi, and Oecusse), and individual in-depth interviews with 24 healthcare providers (16 women, 8 men; aged 25-56 years). Data were analysed using reflexive thematic analysis. Community awareness and understanding about vasectomy were limited, with concerns expressed about physical and social side effects. Healthcare providers had limited experience and knowledge about vasectomy, and about male sexual and reproductive health more generally. However, our findings also indicate a small but existing demand for vasectomy services that could be grown and better met through health systems strengthening initiatives. Insights from our research have informed programmatic decision-making in Timor-Leste and can be further used to inform national health policy and practice.
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ItemPotentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data(ELSEVIER SCI LTD, 2023-09)BACKGROUND: Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry). METHODS: We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018-19), National Aboriginal and Torres Strait Islander Social Survey (2014-15), National Health Survey (2017-18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available. FINDINGS: A large proportion (38·2%, 95% CI 37·2-39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1-46·7) for First Nations Australians, 36·4% (34·8-38·1) for European ancestry, and 33·6% (30·1-37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6-41·6) for all Australians. Physical inactivity (8·3%, 7·5-9·2), hearing loss (7·0%, 6·4-7·6), and obesity (6·6%, 6·0-7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups. INTERPRETATION: Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate. FUNDING: Australian National Health and Medical Research Council and University College London Hospitals' National Institute for Health Research (NIHR) Biomedical Research Centre, and North Thames NIHR Applied Research Collaboration.
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ItemDynamics of belonging amid geographical immobility: a longitudinal analysis of youth trajectories in rural Australia(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2024-01-01)
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ItemVariational Bayesian Neural Networks via Resolution of Singularities(TAYLOR & FRANCIS INC, 2024-01-01)
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ItemLost in translation: a narrative review and synthesis of the published international literature on mental health research and translation priorities (2011-2023)(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.