Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Effectiveness of the Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence of people living with dementia: a multicentre, pragmatic, randomised, open-label, controlled trial.

Background: We investigated the effectiveness of an Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence, health and well-being of people with dementia, family carer outcomes and costs.

Method: A multicentre pragmatic parallel-arm randomised controlled trial compared I-HARP to usual care in community-dwelling people with mild to moderate dementia and their family carers in Sydney, Australia (2018-2022). I-HARP is a 4-month, home-based, dementia rehabilitation model delivered by an interdisciplinary team.

Reduced Breast and Ovarian Cancer Through Targeted Genetic Testing: Estimates Using the NEEMO Microsimulation Model.

The effectiveness and cost-effectiveness of genetic testing for hereditary breast and ovarian cancer largely rely on the identification and clinical management of individuals with a pathogenic variant prior to developing cancer. Simulation modelling is commonly utilised to evaluate genetic testing strategies due to its ability to synthesise collections of data and extrapolate over long time periods and large populations. Existing genetic testing simulation models use simplifying assumptions for predictive genetic testing and risk management uptake, which could impact the reliability of their estimates.

Novel digital droplet inverse PCR assay shows that natural clearance of hepatitis B infection is associated with fewer viral integrations.

Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear.

Integrated solutions for sustainable fall prevention in primary care: a pragmatic hybrid-type 2 mixed methods implementation and effectiveness study.

Unlabelled: The iSOLVE implementation project established and evaluated integrated processes and pathways, including a decision-making tool and educational interventions for general medical practitioners (GPs) and the upskilling of allied health professionals (AHPs). The study used a mixed-methods (parallel) design comprising surveys, qualitative methodologies, and an embedded cluster randomized controlled trial (RCT). Sampling was conducted within a Primary Health Network (PHN) geographic area in Sydney, Australia.

Case Series of Cerebellar Ataxia with Tremor Due to Heterozygous STUB1 Variants (SCA48) without TBP Expansions: Further Evidence for SCA48 as a Monogenic Disease.

Clinically-relevant variants in the STUB1 gene have been associated with an autosomal dominant spinocerebellar ataxia 48 (SCA48), a recently described inherited neurodegenerative condition that is characterised by cognitive and psychiatric changes. To describe the clinical phenotype and genetic findings of three new Australian probands with STUB1 to expand the current understanding of the spectrum of clinical presentation and natural history of SCA48. Clinical and genetic review of patients diagnosed with SCA48 ataxia drawn from our centres.

Association of Lupus Low Disease Activity State And Remission With Reduced Organ Damage And Flare in Systemic lupus erythematosus Patients With High Disease Activity.

Objective: High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes.

Methods: Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed.

Infective Endocarditis in Patients Receiving Hemodialysis: A Current Review.

Background: Cardiovascular and infective complications are commonly observed in patients receiving hemodialysis (HD) with cardiovascular events and infection-related complications being the first and second leading causes of death. Infective endocarditis (IE) is characterized by inflammation of the endocardium caused by infection, typically affecting the cardiac valves and can be in acute, subacute, or chronic forms. It is a serious complication within the HD population due to their predisposition for both infection and valvular damage.

New insights into the impact of bed rest on lumbopelvic muscles: a computer-vision model approach to measure fat fraction changes.

Space agencies plan crewed missions to the Moon and Mars. However, microgravity-induced lumbopelvic deconditioning, characterized by an increased fat fraction (FF) due to reduced physical activity, poses a significant challenge to spine health. This study investigates the spatial distribution of FF in the lumbopelvic muscles to identify the most affected regions by deconditioning, utilizing a computer-vision model and a tile-based approach to assess FF changes.

Evaluation of the Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP) for People Living With Cognitive Impairment and Dementia in Care Homes.

Background: Major knowledge and practice gaps exist in aged care home services to support independence of older people with dementia. This research evaluates an adaptation of a community-based rehabilitation model for care homes, namely Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP), by examining whether (and, if so, how) I-CHARP produces its intended effects and how this programme can be practicably implemented, sustained and scaled up across care homes in Australia.

Methods: I-CHARP is a 4-month bio-behavioural-environmental rehabilitation model of care, integrated in care home services, supported through the deployment of an implementation strategy, the Research Enabled Aged Care Homes (REACH) network.

Metabolic (dysfunction)-associated fatty liver disease metrics and contributions to liver research.

Background: The international consensus to revise non-alcoholic fatty liver disease to metabolic (dysfunction)-associated fatty liver disease (MAFLD) in 2020 attracted significant attention. The impact of the MAFLD definition on the research community has not been objectively assessed. We conducted an analysis of systematically collected literature on MAFLD to understand its research impact.

Muscle Fat and Volume Differences in People With Hip-Related Pain Compared With Controls: A Machine Learning Approach.

Background: Hip-related pain (HRP) affects young to middle-aged active adults and impacts physical activity, finances and quality of life. HRP includes conditions like femoroacetabular impingement syndrome and labral tears. Lateral hip muscle dysfunction and atrophy in HRP are more pronounced in advanced hip pathology, with limited evidence in younger populations.

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.

Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.

Prevalence and Outcomes of Gastrointestinal Manifestations in an Australian Scleroderma Cohort.

Objective: The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes.

Methods: A total of 907 consecutive patients from the Australian Scleroderma Cohort Study who had prospectively completed the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.

"Because that is the right thing to do": A focus group study of Australian expert perspectives on offering smoking cessation support in lung cancer screening.

Introduction: Lung cancer screening (LCS) trials, targeting people with smoking history, have demonstrated reduced mortality. How to optimally embed evidence-based smoking cessation support in LCS, including in Australia, needs to be better understood. We sought experts' perspectives to identify potential barriers and effective implementation strategies.

Qualitative Comparative Analysis of exercise interventions for fall prevention in residential aged care facilities.

Background: Exercise interventions are highly effective at preventing falls in older people living in the community. In residential aged care facilities (RACFs), however, the evidence for effectiveness is highly variable, warranting exploration of drivers of successful trials. This study aims to identify the conditions of randomised controlled trials (RCTs) that are associated with reducing falls in RACFs and test whether it can explain the variability.

Effectiveness of NSW health get healthy telephone coaching in adults screened from general practices.

Background: The effectiveness of the NSW Health "Get Healthy Information and Coaching Service(Get Healthy) to facilitate weight loss on a population scale has been documented, but this was based on self-reported measures. Our study aims to test the effectiveness of the Get Healthy Service on objectively measured weight, BMI, waist circumference, and changes in other health behaviours, including nutrition, physical activity and alcohol intake.

Methods: Men and women aged 40-70 years (n = 154) with pre-diabetes (5.

Ligand-tuning copper in coordination polymers for efficient electrochemical C-C coupling.

Cu catalyses electrochemical CO reduction to valuable multicarbon products but understanding the structure-function relationship has remained elusive due to the active Cu sites being heterogenized and under dynamic re-construction during electrolysis. We herein coordinate Cu with six phenyl-1H-1,2,3-triazole derivatives to form stable coordination polymer catalysts with homogenized, single-site Cu active sites. Electronic structure modelling, X-ray absorption spectroscopy, and ultraviolet-visible spectroscopy show a widely tuneable Cu electronics by modulating the highest occupied molecular orbital energy of ligands.