Why are fish oil supplements apparently failing to reproduce fish consumption epidemiology in RCT for cardiovascular disease?

Abstract of a presentation

School-based HPV vaccination positively impacts parents’ attitudes toward adolescent vaccination

Introduction This qualitative study aimed to explore parental attitudes, knowledge and decision-making about HPV vaccination for adolescents in the context of a gender-neutral school-based Australian National Immunisation Program (NIP). Methods Semi-structured interviews with parents of adolescents eligible for HPV vaccination were undertaken as part of an evaluation of a cluster-randomised controlled trial of a complex intervention in 40 schools (2013–2015). In this qualitative study, we purposively recruited a nested sample of parents from 11 schools across two Australian jurisdictions. Interviews explored parent knowledge and understanding of the HPV vaccine program; HPV vaccination decision-making; their adolescent’s knowledge about HPV vaccination; and their adolescent’s understanding about HPV vaccination, sexual awareness and behaviour. Transcripts were analysed using inductive and deductive thematic analysis. Results Parents’ of 22 adolescents had positive attitudes towards the program; the school-based delivery platform was the key driver shaping acceptance of and decision-making about HPV vaccination. They had difficulty recalling, or did not read, HPV vaccination information sent home. Some adolescents were involved in discussions about vaccination, with parents’ responsible for ultimate vaccine decision-making. All parents supported in-school education for adolescents about HPV and HPV vaccination. Parents’ knowledge about HPV vaccination was limited to cervical cancer and was largely absent regarding vaccination in males. Conclusions Parents’ positive attitudes towards the NIP and inclusion of the HPV vaccine is central to their vaccine decision-making and acceptance. More intensive communication strategies including school education opportunities are required to improve parents’ knowledge of HPV-related disease and to promote vaccine decision-making with adolescents

RNF12 X-linked intellectual disability mutations disrupt E3 ligase activity and neural differentiation

Summary: X-linked intellectual disability (XLID) is a heterogeneous syndrome affecting mainly males. Human genetics has identified >100 XLID genes, although the molecular and developmental mechanisms underpinning this disorder remain unclear. Here, we employ an embryonic stem cell model to explore developmental functions of a recently identified XLID gene, the RNF12/RLIM E3 ubiquitin ligase. We show that RNF12 catalytic activity is required for proper stem cell maintenance and neural differentiation, and this is disrupted by patient-associated XLID mutation. We further demonstrate that RNF12 XLID mutations specifically impair ubiquitylation of developmentally relevant substrates. XLID mutants disrupt distinct RNF12 functional modules by either inactivating the catalytic RING domain or interfering with a distal regulatory region required for efficient ubiquitin transfer. Our data thereby uncover a key function for RNF12 E3 ubiquitin ligase activity in stem cell and neural development and identify mechanisms by which this is disrupted in intellectual disability. : Bustos et al. show that the RNF12 E3 ubiquitin ligase regulates stem cell maintenance and neuronal differentiation. They demonstrate that RNF12/RLIM mutations identified in X-linked intellectual disability patients disrupt regions required for catalytic activity, which leads to compromised stem cell maintenance and abnormal neural differentiation. Keywords: ubiquitin, protein ubiquitylation, E3 ubiquitin ligase, proteasomal degradation, RNF12/RLIM, intellectual disability, X-linked intellectual disability, embryonic stem cells, neural differentiatio

Attitudes about and access to influenza vaccination experienced by parents of children hospitalised for influenza in Australia

INTRODUCTION:In Australia, influenza hospitalises more children than any other vaccine preventable disease does. Children aged six months or older are recommended to receive annual influenza vaccines, and pregnant women are recommended vaccination to protect infants aged up to six months. However, vaccine uptake is low. This study explored influenza vaccination knowledge and behaviours of parents of children who were hospitalised for influenza, in order to inform strategies that target barriers to uptake. METHODS:We conducted 27 semi-structured interviews with parents/caregivers during or shortly after their child's hospitalisation for laboratory-confirmed influenza in 2017. Questions were guided by the Social Ecological Model exploring all levels of influence on vaccination uptake from the intrapersonal through to policy, via the parents' perspective. Transcripts were inductively analysed. Themes were categorised into the components of the Capability-Opportunity-Motivation-Behaviour (COM-B) model. RESULTS:20/27 children were aged six months or older; 16/20 had not received an influenza vaccine in 2017. Mothers of 4/7 infants aged less than six months were not vaccinated in pregnancy. The themes regarding barriers to influenza vaccination were: (1) Limited Capability - misinterpretations and knowledge gaps, (2) Lack of Opportunity - inconvenient vaccination pathway, missing recommendations, absence of promotion to all, and the social norm, and (3) Missing Motivation - hierarchy of perceived seriousness, safety concerns, a preference for 'natural' ways. Though most parents, now aware of the severity of influenza, intended to vaccinate their child in future seasons, some harboured reservations about necessity and safety. When parents were asked how to help them vaccinate their children, SMS reminders and information campaigns delivered through social media, schools and childcare were suggested. CONCLUSION:Improving parents' and providers' knowledge and confidence in influenza vaccination safety, efficacy, and benefits should be prioritised. This, together with making influenza vaccination more convenient for parents, would likely raise vaccine coverage.Samantha J Carlson, Camilla Scanlan, Helen S Marshall, Christopher C Blythd, Kristine Macartney, Julie Leas

Addressing inequitable access to hospice care

The ‘Lancet Commission on the Value of Death’ proposes radical change and challenges the very core of hospice service provision. Without action, inequalities in access to hospice care will continue to be amplified. The COVID pandemic brought increased needs and demands in the community setting but also provided opportunities for new palliative partnerships and ways of working. Returning to the status quo should not be an option. Rather moving towards a shared vision and purpose, which has the person and their community network at its centre, enables hospices to have a pivotal role and bring about more equitable palliative care

Pneumococcal vaccination uptake among patients aged 65 years or over in Australian general practice

In Australia, pneumococcal vaccine is provided free to all adults aged ≥65 years and Indigenous people aged 15-65 years, and is subsidised for non-Indigenous adults <65 years of age with risk factors. This study aimed to explore pneumococcal vaccination uptake in older patients attending 550 Australian general practice from 2010-2017 by patient sociodemographics, presence of comorbidities and practice characteristics. Study 1: a cross-sectional analysis of 'active' patients aged ≥65 years in each year was performed to calculate annual pneumococcal vaccination uptake. Study 2: a cohort of 58,589 'every year' patients aged 60-65 years in 2010 was analysed to identify the number of patients immunised during the study period. Logistic regression models assessed associations between vaccination, patient and practice characteristics. Annual pneumococcal vaccine uptake varied by patient's age (65-74 or ≥75 years), presence of comorbidities and regularity of practice visits (range 36% to 76%), and it declined slowly from 2011-2016 amongst all groups. Cohort analyses showed that 69% of those aged 60-65 years in 2010 had a recorded pneumococcal vaccination by 2017 (peak age of vaccination = 66 years), and vaccination was more likely among those with comorbidities, ex-smokers and frequent attenders to practices. Findings demonstrate that the NPS MedicineInsight database provides estimates of vaccination uptake consistent with past surveys, reproducible every year and at low cost. It has the advantage of additional clinical information compared to the Australian Immunisation Register. Whilst vaccination uptake was adequate among 'every year' patients, interventions are needed to improve pneumococcal vaccination for all older Australians.Oliver Frank, Carla De Oliveira Bernardo, David Alejandro González-Chica, Kristine Macartney, Robert Menzies and Nigel Stock

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.Karina A Top, Kristine Macartney, Julie A Bettinger, Ben Tan, Christopher C Blyth, Helen S Marshall ... et al. (on behalf of the IMPACT and PAEDS investigators

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2 mediated Rab protein phosphorylation in mouse and human

Missense mutations in the LRRK2 and VPS35 genes result in autosomal dominant Parkinson’s disease. The VPS35 gene encodes for the cargo-binding component of the retromer complex, while LRRK2 modulates vesicular trafficking by phosphorylating a subgroup of Rab proteins. Pathogenic mutations in LRRK2 increase its kinase activity. It is not known how the only thus far described pathogenic VPS35 mutation, [D620N] exerts its effects. We reveal that the VPS35[D620N] knock-in mutation, strikingly elevates LRRK2 mediated phosphorylation of Rab8A, Rab10 and Rab12 in mouse embryonic fibroblasts. The VPS35[D620N] mutation also increases Rab10 phosphorylation in mouse tissues (lung, kidney, spleen and brain). Furthermore, LRRK2 mediated Rab10 phosphorylation is increased in neutrophils as well as monocytes isolated from three Parkinson’s patients with a heterozygous VPS35[D620N] mutation compared to healthy donors and idiopathic Parkinson’s patients. LRRK2 mediated Rab10 phosphorylation is significantly suppressed by knock-out or knock-down of VPS35 in wild type, LRRK2[R1441C] or VPS35[D620N] cells. Finally, VPS35[D620N] mutation promotes Rab10 phosphorylation more potently than LRRK2 pathogenic mutations. Available data suggest that Parkinson’s patients with VPS35[D620N] develop the disease at a younger age than those with LRRK2 mutations. Our observations indicate that VPS35 controls LRRK2 activity and that the VPS35[D620N] mutation results in a gain of function, potentially causing Parkinson’s disease through hyperactivation of the LRRK2 kinase. Our findings suggest that it may be possible to elaborate compounds that target the retromer complex to suppress LRRK2 activity. Moreover, patients with VPS35[D620N] associated Parkinson’s might benefit from LRRK2 inhibitor treatment that have entered clinical trials in humans