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Nurse home visiting (NHV) is widely implemented to address inequities in child and maternal health. However, few studies have examined longer-term effectiveness or delivery within universal healthcare systems. We evaluated the benefits of an Australian NHV program (\"right@home\") in promoting children's language and learning, general and mental health, maternal mental health and wellbeing, parenting and family relationships, at child ages 4 and 5 years. Randomised controlled trial of NHV delivered via universal, child and family health services (the comparator). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states (Victoria, Tasmania) in Australia. Mothers in the intervention arm were offered 25 nurse home visits (mean 23·2 home visits [SD 7·4, range 1-43] received) of 60-90 minutes, commencing antenatally and continuing until children's second birthdays. At 4 and 5 years, outcomes were assessed via parent interview and direct assessment of children's language and learning (receptive and expressive language, phonological awareness, attention, and executive function). Outcomes were compared between intervention and usual care arms (intention to treat) using adjusted regression with robust estimation to account for nurse/site. Missing data were addressed using multiple imputation and inverse probability weighting. Of 722 women enrolled in the trial, 225 of 363 (62%) intervention and 201 of 359 (56%) usual care women provided data at 5 years. Estimated group differences showed an overall pattern favouring the intervention. Statistical evidence of benefits was found across child and maternal mental health and wellbeing, parenting and family relationships with effect sizes ranging 0·01-0·27. An Australian NHV program promoted longer-term family functioning and wellbeing for women experiencing adversity. NHV can offer an important component of a proportionate universal system that delivers support and intervention relative to need. 2013-2016, registration ISRCTN89962120.

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule with a dual role: it transfers electrons in the mitochondrial transport chain by promoting the transmembrane potential exploited by the ATPase to synthesize ATP and, in its reduced form, is a membrane antioxidant. Since the high CoQ10 hydrophobicity hinders its bioavailability, several formulations have been developed to facilitate its cellular uptake. In this work, we studied the bioenergetic and antioxidant effects in I407 and H9c2 cells of a CoQ10 phytosome formulation (UBIQSOME®, UBQ). We investigated the cellular and mitochondrial content of CoQ10 and its redox state after incubation with UBQ. We studied different bioenergetic parameters, such as oxygen consumption, ATP content and mitochondrial potential. Moreover, we evaluated the effects of CoQ10 incubation on oxidative stress, membrane lipid peroxidation and ferroptosis and highlighted the connection between the intracellular concentration of CoQ10 and its antioxidant potency. Finally, we focused on the cellular mechanism that regulates UBQ internalization. We showed that the cell lines used in this work share the same uptake mechanism for UBQ, although the intestinal cell line was less efficient. Given the limitations of an in vitro model, the latter result supports that intestinal absorption is a critical step for the oral administration of Coenzyme Q10 formulations.

Background and objectives The Mediterranean Diet (MD) has been recognized for its benefits for human health and sustainability for the planet, but it has considered not easy to reproduce in other populations. The United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair on Health Education and Sustainable Development is fostering a research project (Planeterranea), aiming to identify a healthy dietary pattern based on local foods with the same MD features. The aim of our study is to develop a MD-based food pyramid for Asian populations. Methods Asia was stratified into six areas according to pedo-climatic conditions. For each region a comprehensive scoping review of local crops and typical foods was conducted on several databases such as the US Department of Agriculture (USDA)’s database, the Food and Agriculture Organization of the United Nations (FAO) website, and PubMed, focusing on both plant-based and animal-based foods. Narrative review was then conducted on the identified foods to determine their nutritional composition and planetary health impact. Finally, the collected information was used to build up the Asian food pyramid with details for each respective region. Results We proposed a food pyramid for Asian countries, guaranteeing the same nutritional intake and health benefits as MD, by considering dietary habits and typical foods of this population. From the bottom to the top, Asian fruits and vegetables present similar nutritional profile as those in MD. Whole grains (barley) may represent valid alternative to white rice. Sesame oil represents a source of unsaturated fats and an alternative to olive oil. Legumes (soybean), edible insects, mushrooms and algae, guarantee an adequate intake of plant-based proteins with a complete amino-acid profile and a low environmental impact with respect to animal-based ones. Conclusions This work is a new insight of healthy and sustainable local food system based on MD principles for the Asian population.

Statins are the first-line therapy for managing elevated cholesterol levels that represent a risk of acute cardiovascular events. However, the use of statins is associated with several side effects, likely due to the depletion of Coenzyme Q10 (CoQ10), a key component of the mitochondrial electron transport chain and a membrane antioxidant. In our study, we present evidence of the cytotoxic effects of Atorvastatin on human dermal fibroblasts in terms of oxidative stress and mitochondrial impairment. Interestingly, CoQ10 supplementation in statin-treated cells significantly reduced ROS levels and restored mitochondrial oxygen consumption rate and the intracellular ATP/ADP ratio. Moreover, our data suggest that the mechanism for Atorvastatin off-target effects at high concentrations involves the inhibition of respiratory complexes I and III, leading to reverse electron transport and ROS production by Complex I. These findings highlight the potential benefits of CoQ10 supplementation in mitigating statin-induced cytotoxicity and propose a mechanistic basis for the adverse effects associated with Atorvastatin therapy.

This essay questions the geographical categories used to underpin current theoretical and methodological approaches to “world literature,” which end up making nine-tenths of the world, and of literature produced in the world, drop off the world map or appear “peripheral.” Focusing on the multilingual north Indian region of Awadh in the early modern period, it argues that an approach to literature and space that takes multilingualism within society and literary culture as a structuring and generative principle and holds local cosmopolitan perspectives in view is more productive for world literature than approaches based only on cosmopolitan perspectives of circulation and recognition.

Objectives Nurse home visiting (NHV) is widely implemented to address inequities in child and maternal health. However, few studies have examined longer-term effectiveness or delivery within universal healthcare systems. We evaluated the benefits of an Australian NHV program (“right@home”) in promoting children’s language and learning, general and mental health, maternal mental health and wellbeing, parenting and family relationships, at child ages 4 and 5 years. Setting and participants Randomised controlled trial of NHV delivered via universal, child and family health services (the comparator). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states (Victoria, Tasmania) in Australia. Intervention Mothers in the intervention arm were offered 25 nurse home visits (mean 23·2 home visits [SD 7·4, range 1–43] received) of 60–90 minutes, commencing antenatally and continuing until children’s second birthdays. Primary and secondary outcomes measured At 4 and 5 years, outcomes were assessed via parent interview and direct assessment of children’s language and learning (receptive and expressive language, phonological awareness, attention, and executive function). Outcomes were compared between intervention and usual care arms (intention to treat) using adjusted regression with robust estimation to account for nurse/site. Missing data were addressed using multiple imputation and inverse probability weighting. Results Of 722 women enrolled in the trial, 225 of 363 (62%) intervention and 201 of 359 (56%) usual care women provided data at 5 years. Estimated group differences showed an overall pattern favouring the intervention. Statistical evidence of benefits was found across child and maternal mental health and wellbeing, parenting and family relationships with effect sizes ranging 0·01–0·27. Conclusion An Australian NHV program promoted longer-term family functioning and wellbeing for women experiencing adversity. NHV can offer an important component of a proportionate universal system that delivers support and intervention relative to need. Trial registration 2013–2016, registration ISRCTN89962120

Background Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. Methods Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. Results For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian’s agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day. Conclusions Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.

Background Understanding how and why de-implementation of low-value practices is sustained remains unclear. The Paediatric Research in Emergency Departments International CollaboraTive (PREDICT) Bronchiolitis Knowledge Translation (KT) Study was a cluster randomised controlled trial conducted in 26 Australian and New Zealand hospitals (May-November 2017). Results showed targeted, theory-informed interventions (clinical leads, stakeholder meetings, train-the-trainer workshop, targeted educational package, audit/feedback) were effective at reducing use of five low-value practices for bronchiolitis (salbutamol, glucocorticoids, antibiotics, adrenaline and chest x-ray) by 14.1% in acute care settings. The primary aim of this study is to determine the sustainability (continued receipt of benefits) of these outcomes at intervention hospitals two-years after the removal of study supports. Secondary aims are to determine sustainability at one-year after removal of study support at intervention hospitals; improvements one-and-two years at control hospitals; and explore factors that influence sustainability at intervention hospitals and contribute to improvements at control hospitals. Methods A mixed-methods study design. The quantitative component is a retrospective medical record audit of bronchiolitis management within 24 hours of emergency department (ED) presentations at 26 Australian ( n  = 20) and New Zealand ( n  = 6) hospitals, which participated in the PREDICT Bronchiolitis KT Study. Data for a total of 1800 infants from intervention and control sites (up to 150 per site) will be collected to determine if improvements (i.e., no use of all five low-value practices) were sustained two- years (2019) post-trial (primary outcome; composite score); and a further 1800 infants from intervention and control sites will be collected to determine sustained improvements one- year (2018) post-trial (secondary outcome). An a priori definition of sustainability will be used. The qualitative component will consist of semi-structured interviews with three to five key emergency department and paediatric inpatient medical and nursing staff per site (total n  = 78-130). Factors that may have contributed to sustaining outcomes and/or interventions will be explored and mapped to an established sustainability framework. Discussion This study will improve our understanding of the sustainability of evidence-based bronchiolitis management in infants. Results will also advance implementation science research by informing future de-implementation strategies to reduce low-value practices and sustain practice change in paediatric acute care. Trial registration Australian and New Zealand Clinical Trials Registry No: ACTRN12621001287820.

Background Gabapentin is often used to manage pain in children with dystonic cerebral palsy, however the evidence for its effectiveness in this population is limited. The primary objective of this feasibility pilot study was to assess the factors which might impact on a future randomised controlled trial including the ability to recruit and retain participants, assess adherence/compliance to the prescribed intervention, and ability to complete all outcome assessments. The secondary objective was to gather preliminary evidence for the effectiveness of gabapentin at reducing pain, improving comfort and reducing dystonia in children with dystonic cerebral palsy. Methods This open label pilot study recruited children aged 5–18 years with dystonic cerebral palsy and accompanying pain affecting daily activities from four centres around Australia. Children were prescribed gabapentin for 12 weeks and were assessed at baseline, 6 weeks and 12 weeks. The primary outcome was feasibility of the protocol. Secondary outcomes were pain behaviour, pain intensity, care and comfort, individualised goal setting and dystonia severity. Results Thirteen children (mean age 10.4 years (SD 2.4yrs), 9 females) were recruited from 71 screened over 15 months. Two children withdrew while eight children experienced side effects. There were issues with adherence to medication dosage regimens and data collection. Improvements were seen in pain behaviour, comfort and pain related goals at 12 weeks. Dystonia was not significantly changed. Conclusions Whilst gabapentin has potential to improve pain and comfort in children with dystonic CP, the feasibility of implementing a definitive randomised controlled trial is low. Alternative trials designs are required to further examine the effectiveness of gabapentin in this heterogeneous population. Trial registration The trial was registered with the Australian Clinical Trial Registry ( ACTRN12616000366459 ) on 22/03/2016 and the Therapeutic Goods Administration (CT-2016-CTN-00500-1) on 22/06/2016.

Background Bronchiolitis is the most common reason for hospitalisation in infants. All international bronchiolitis guidelines recommend supportive care, yet considerable variation in practice continues with infants receiving non-evidence based therapies. We developed six targeted, theory-informed interventions; clinical leads, stakeholder meeting, train-the-trainer, education delivery, other educational materials, and audit and feedback. A cluster randomised controlled trial (cRCT) found the interventions to be effective in reducing use of five non-evidence based therapies in infants with bronchiolitis. This process evaluation paper aims to determine whether the interventions were implemented as planned (fidelity), explore end-users’ perceptions of the interventions and evaluate cRCT outcome data with intervention fidelity data. Methods A pre-specified mixed-methods process evaluation was conducted alongside the cRCT, guided by frameworks for process evaluation of cRCTs and complex interventions. Quantitative data on the fidelity, dose and reach of interventions were collected from the 13 intervention hospitals during the study and analysed using descriptive statistics. Qualitative data identifying perception and acceptability of interventions were collected from 42 intervention hospital clinical leads on study completion and analysed using thematic analysis. Results The cRCT found targeted, theory-informed interventions improved bronchiolitis management by 14.1%. The process evaluation data found variability in how the intervention was delivered at the cluster and individual level. Total fidelity scores ranged from 55 to 98% across intervention hospitals (mean = 78%; SD = 13%). Fidelity scores were highest for use of clinical leads (mean = 98%; SD = 7%), and lowest for use of other educational materials (mean = 65%; SD = 19%) and audit and feedback (mean = 65%; SD = 20%). Clinical leads reflected positively about the interventions, with time constraints being the greatest barrier to their use. Conclusion Our targeted, theory-informed interventions were delivered with moderate fidelity, and were well received by clinical leads. Despite clinical leads experiencing challenges of time constraints, the level of fidelity had a positive effect on successfully de-implementing non-evidence-based care in infants with bronchiolitis. These findings will inform widespread rollout of our bronchiolitis interventions, and guide future practice change in acute care settings. Trial registration Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415 .