Towards best practice during COVID-19: A responsive and relational program with remote schools to enhance the wellbeing of Aboriginal and Torres Strait Islander students.

Purpose: From 2018, the Schools Up North (SUN) programme worked with three remote Australian schools to enhance their capability and resilience to support the wellbeing and mental health of Aboriginal and Torres Strait Islander students and staff. This paper explores the implementation of SUN during the first two years of COVID-19 (2020-2021). Method: Using grounded theory methods, school staff, other service providers and SUN facilitators were interviewed, with transcripts and programme documents coded and interrelationships between codes identified. An implementation model was developed. Results: The SUN approach was place-based, locally informed and relational, fostering school resilience through staff reflection on and response to emerging contextual challenges. Challenges were the: community lockdowns and school closures; (un)availability of other services; community uncertainty and anxiety; school staff capability and wellbeing; and risk of educational slippage. SUN strategies were: enhancing teachers' capabilities and resources, facilitating public health discussions, and advocating at regional level. Outcomes were: enhanced capability of school staff; greater school-community engagement; student belonging and engagement; a voice for advocacy; and continuity of SUN's momentum. Conclusions: The resilience approach (rather than specific strategies) was critical for building schools' capabilities for promoting students and staff wellbeing and provides an exemplar for remote schools globally.

Airway-related symptoms and surgeries in patients with mucopolysaccharidosis I.

OBJECTIVE: Mucopolysaccharidosis I (MPS I) is a progressive, debilitating, and life-threatening genetic disease, which, owing to the nonspecific nature of the early symptoms, is often unrecognized and associated with significant diagnostic delays. To improve early recognition leading to early diagnosis and initiation of treatment, we characterized the extent of airway-related symptoms and surgeries among patients with MPS I. METHODS: Analysis of the frequency of airway-related symptoms and surgeries from 1041 patients enrolled in the MPS I Registry and correlation with other systemic manifestations of MPS I. RESULTS: Airway-related symptoms (macroglossia, enlarged tonsils, reactive airway disease/asthma, or sleep disturbances) were reported for as many as 85% of Hurler, 83% of Hurler-Scheie, and 65% of Scheie patients-very often before the diagnosis of MPS I was established. Surgeries for an airway indication were reported in 39% of patients and many had at least 1 airway-related surgery before the diagnosis of MPS I was confirmed. The mean percentage of patients with airway-related symptoms for whom hernias and/or dysostosis multiplex were also reported was 84% and 54%, respectively. CONCLUSION: Airway-related symptoms and surgeries are common and often the earliest presenting feature in MPS I. Improved recognition of early MPS I disease manifestations may lead to earlier diagnosis and treatment.

Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program.

OBJECTIVE: The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA). METHODS: This was an analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 OCR phase III trials in RA (SCRIPT, STAGE, FILM and FEATURE). Safety data per study and the results of a meta-analysis of serious infectious events (SIEs) are presented. RESULTS: Overall, 868 patients received placebo, 1064 patients OCR 200 mg×2 (or 400 mg×1) (OCR200), and 827 patients OCR 500 mg×2 (OCR500) plus background methotrexate (MTX) at baseline and 24 weeks. During the double-blind, placebo-controlled periods, the incidence of adverse events and serious adverse events was comparable between the OCR+MTX and placebo +MTX groups. Infusion-related reactions were more common with OCR+MTX and decreased in frequency with subsequent infusions. Serious infusion-related reactions were rare (0.1%). Serious infections occurred more frequently with OCR500+MTX. In the meta-analysis, a statistically significant difference from placebo +MTX in incidence of SIEs per 100 patient-years of 2.4 (95% CI, 0.3-4.5) was observed with OCR500+MTX, but not with OCR200+MTX (0.6; 95% CI, -1.3 to 2.4). Patients recruited in Asia exhibited a higher risk of serious infections (hazard ratio, 1.78; 95% CI, 1.03-3.06). The incidence of human anti-human antibodies was <5%. Long-term follow-up indicated no differences in malignancy rates between the treatment groups. There was no apparent difference in time to B-cell repletion between the OCR dose groups. CONCLUSIONS: In placebo-controlled clinical trials of RA, OCR500+MTX was associated with a higher risk of serious infections compared with placebo +MTX. The safety profile of OCR 200+MTX was comparable with placebo+MTX. TRIAL REGISTRATION: STAGE ClinicalTrials.gov NCT00406419 SCRIPT ClinicalTrials.gov NCT00476996 FILM ClinicalTrials.gov NCT00485589 FEATURE ClinicalTrials.gov NCT00673920.

Performative evaluation and social return on investment: potential in innovative health promotion interventions.

OBJECTIVE: The purpose of this study was to describe an approach to evaluation of a project involving complex health behaviours that incorporates collateral social outcomes. METHOD: Evaluation challenges and responses for an innovative information and communication technologies for development (ICT4D) initiative (HITnet) operating in remote Indigenous Australia are presented. CONCLUSIONS: Innovation in evaluation must match innovation in project design and application. Two methodologies--performative research, and social return on investment--as proposed for a HITnet, sexual health promotion project, are considered.

Empowerment and change management in Aboriginal organisations: a case study.

The social organisation of work, management styles and social relationships in the workplace all matter for health. It is now well recognised that people who have control over their work have better health and that stress in the workplace increases the level of disease. In the context of organisational change, the potential benefits of empowerment strategies are two-fold: a positive impact on the organisation's effectiveness and enhancements in staff health, wellbeing and sense of control. This case study describes the University of Queensland Empowerment Research Program's experience working with the Apunipima Cape York Health Council in a change management process. Participatory action research and empowerment strategies were utilised to facilitate shifts in work culture and group cohesion towards achieving Apunipima's vision of being an effective lead agency for Indigenous health reform in Cape York. As part of the project, staff morale and confidence were monitored using a pictorial tool, Change Curve, which outlined the phases of organisational change. The project findings indicated that organisational change did not follow a clear linear trajectory. In some ways the dynamics mapped over a period of 18 months mirror the type of struggles individuals commonly encounter as a part of personal growth and development. In this case, one of the factors which influenced the program's success was the willingness of executive employees to actively support and participate in the change management process.

Pride and performance: evaluation challenges of a multimedia and information technologies project in remote Aboriginal Australia.

OBJECTIVES: This paper explores an approach to an evaluation challenge: to demonstrate the impact of an initiative drawing on innovative use of information/multimedia technology and performance to address perceived social needs within a disadvantaged, remote Indigenous Australian community. RESULTS: The approach is described and preliminary data are presented supporting the importance of local production and participation.

Out of a digital chrysalis: NIHNMF (pronounced nymph--the National Indigenous Health and New Media Forum).

In conjunction with the Creating Futures conference, the inaugural meeting of the National Indigenous Health and New Media Forum (NIHNMF--pronounced as 'nymph') was held at the Tanks Gallery in Cairns, Queensland, Australia. This paper describes the background to this innovative meeting of media minds. It also explores an emerging vision for addressing Indigenous health disparities through digital inclusion to overcome the 'digital divide' between mainstream and Indigenous Australians that constrains the delivery of appropriate health promotion to this health priority population.

Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis.

OBJECTIVE: To determine the efficacy and safety of pamapimod (a selective inhibitor of the alpha-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA). METHODS: Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs. RESULTS: Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX. CONCLUSION: The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.

Bridging the triple divide: performance and innovative multimedia in the service of behavioural health change in remote Indigenous settings.

OBJECTIVES: The use of innovative information technology is now well established in health. However, while the gap in health status between Indigenous and other Australians is both significant and unchanging, there is limited application of these new approaches to addressing this national health priority. This may in part reflect the 'digital divide', which is another facet of Indigenous disadvantage. This paper describes an approach to address both issues in remote Indigenous settings. RESULTS: The Health Interactive Technology Network began as a proof-of-concept study of touchscreen technology in two Indigenous health settings. It has subsequently expanded to a number of remote Indigenous communities and developed new platforms and applications to respond to emerging health issues. In creating narrative, interactive approaches to address choices in relation to health behaviours, the community development and engagement effects of the creative process have been highlighted. These findings suggest that these approaches will be suited to further expansion in the area of mental health.

Human CD34+ hematopoietic progenitor cells hyperacetylate core histones in response to sodium butyrate, but not trichostatin A.

Cells positive for the cell surface marker CD34 from bone marrow or umbilical cord blood form a subset of quiescent, hematopoetic precursors that can establish human hematopoesis in immunodeficient mice and can progress down various differentiation pathways in vitro. They provide a valuable model system in which progression from quiescent to cycling to differentiated states can be linked to changes in chromatin and histone modification. We have used the deacetylase inhibitor sodium butyrate to show that turnover of histone H4 acetates is rapid and comparable in quiescent and cycling CD34+ cells from human umbilical cord blood (CD34+ UBC). Surprisingly, the widely used inhibitor trichostatin A (TSA) had little (cycling cells) or no (quiescent cells) effect on H4 acetylation in CD34+ UBC. Among five cell types examined, CD34+ UBC were unique in expressing all (putative) deacetylases tested (HDAC1, -2, -3, -4, -6, -7, and -8 and SIRT1-4), but no single deacetylase correlated with their TSA resistance. Also, HDAC1, -2, -3, and -6 complexes isolated from CD34+ UBC by immunoprecipitation were all inhibited by TSA in vitro. Thus, TSA resistance of CD34+ UBC is not due to acquired or intrinsic TSA resistance of their deacetylases and may reflect an enhanced ability to process the drug.