High circulating concentrations of estradiol are anabolic for bone mass and strength in an adult male to female transgender mouse model.

The effects of gender affirming hormone therapy (GAHT) on bone microarchitecture and fracture risk in adult transgender women is unclear. To investigate the concept that skeletal integrity and strength in trans women may be improved by treatment with a higher dose of GAHT than commonly prescribed, we treated adult male mice with a sustained, high dose of estradiol. Adult male mice at 16 weeks of age were administered ~1.3 mg estradiol by silastic implant, implanted intraperitoneally, for 12 weeks. Controls included vehicle treated intact females and males. High-dose estradiol treatment in males stimulated the endocortical deposition of bone at the femoral mid-diaphysis, increasing cortical thickness and bone area. This led to higher stiffness, maximum force, and the work required to fracture the bone compared to male controls, while post-yield displacement was unaffected. Assessment of the material properties of the bone showed an increase in both elastic modulus and ultimate stress in the estradiol treated males. Treatment of male mice with high dose estradiol was also anabolic for trabecular bone, markedly increasing trabecular bone volume, number and thickness in the distal metaphysis which was accompanied by an increase in the histomorphometric markers of bone remodelling, mineralizing surface/bone surface, bone formation rate and osteoclast number. In conclusion, a high dose of estradiol is anabolic for cortical and trabecular bone in a male to female transgender mouse model, increasing both stiffness and strength. These findings suggest that increasing the current dose of GAHT administered to trans women, while considering other potential adverse effects, may be beneficial to preserving their bone microstructure and strength.

Validity of the Active Australia Survey in an Australian cardiac rehabilitation population.

OBJECTIVES: To examine the long-term validity of the Active Australia Survey in a cardiac rehabilitation population using accelerometry as the reference measure. DESIGN: Cohort validation study. METHODS: Cardiac rehabilitation participants with coronary heart disease were recruited to a prospective cohort study. Over 7-days, 61 participants wore an ActiGraph ActiSleep accelerometer (1-second epoch, 10-minute bout) and completed the self-administered Active Australia Survey at baseline, 6-weeks, 6 and 12-months. Total daily moderate-to-vigorous physical activity from both methods was compared using Bland-Altman plots and Spearman rank-order correlations. RESULTS: Participants tended to over-report moderate-to-vigorous physical activity, with more active participants more likely to over-report moderate-to-vigorous physical activity. There was a good level of agreement between the accelerometer 1-second epochs and Active Australia Survey at all time points (mean bias (ratio) 1.04, 1.16, 1.14, and 1.06, respectively), with weak-moderate correlations (ρ = 0.3-0.48). Conversely, there was a poor level of agreement between the accelerometer 10-minute bouts and Active Australia Survey at all time points (mean bias (ratio) 6.78, 9.09, 6.35, and 5.68, respectively), with weak-moderate correlations (ρ = 0.3-0.52). Agreement between the two measures did not improve over time for both 1-second and 10-minute bout accelerometry data. CONCLUSIONS: The Active Australia Survey may be an acceptable self-report measure of moderate-to-vigorous physical activity in cardiac rehabilitation attendees when capturing any time spent in moderate-to-vigorous physical activity. The Active Australia Survey may be useful to routinely monitor physical activity levels over-time in Australian cardiac rehabilitation programs at both individual and group levels. TRIAL REGISTRATION: Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12615000995572, http://www.ANZCTR.org.au/ACTRN12615000995572.aspx.

Activity counseling early postelective percutaneous coronary intervention (ACE-PCI): Mixed-methods pilot randomized controlled trial.

Background: Physical activity (PA) levels of people with coronary heart disease are low in the first 30 days after percutaneous coronary intervention (PCI), increasing the risk of recurrent cardiac events. Following PCI, PA counseling delivered by a physiotherapist before discharge may increase the PA levels of patients. Preliminary work is required to determine the effects of the counseling session compared to usual care. Objectives: To investigate the feasibility and potential efficacy of a brief physiotherapist-led PA counseling session immediately after an elective PCI compared to usual care for improved PA early post-PCI. Methods: Using concealed allocation and blinded assessments, eligible participants (n = 30) were randomized to a physiotherapist-led PA counseling session (30 min) or usual care (nurse-led PA advice < 5 min). The primary outcome was daily minutes of moderate-to-vigorous PA (accelerometry; 3 weeks). Secondary outcomes included cardiac rehabilitation intention, anxiety and depression levels (Hospital Anxiety and Depression Scale), and quality-of-life (MacNew questionnaire). Recruitment, retention, and attrition were assessed for feasibility. Semistructured interviews were conducted with 13 participants to determine intervention acceptability, and barriers and enablers to PA. Results: Between and within-group comparisons were not significant in intention-to-treat analyses. All feasibility criteria were met except for retention and attrition of participants. At 3 weeks, only 25% of participants were planning to attend cardiac rehabilitation, with no between-group differences. Increased PA at 3 weeks was associated with participants that were younger, without other chronic disease,s and more active immediately following discharge. Interviews revealed personal, environmental, and program-based themes for barriers and enablers to PA. Conclusions: A physiotherapist-led PA counseling session may not improve PA levels early post-elective PCI compared to very brief PA advice delivered by nurses. A larger multicentre randomized controlled trial is feasible with minor modifications to participant follow-up. Further research is required.

Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy.

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.

A metasynthesis of nurses and midwives' experiences of clinical supervision.

PROBLEM: Given the current rate of burnout and attrition among nurses and midwives globally, there is a need to understand the effectiveness of supportive strategies to help retain this workforce. BACKGROUND: Clinical supervision can help to ensure that nurses and midwives are supported and have the capacity to cope with their job demands. Yet there are no metasyntheses that provide a collective understanding of their experiences with clinical supervision. AIM: To synthesise the experiences of nurses and midwives who have accessed clinical supervision. METHODS: A metasynthesis was conducted by systematically searching academic databases for relevant publications; assessing their quality using an established checklist; extracting and analysing qualitative content; and synthesising key findings about the experiences of nurses and midwives regarding clinical supervision. FINDINGS: Themes and subthemes were identified from 12 papers, including: optimal logistics; support; safety and confidentiality; improving practice through reflection; and trust in the group. DISCUSSION: For clinicians to feel comfortable discussing their practice and workplace with the facilitator and colleagues, nurses and midwives needed to feel safe during clinical supervision and trust the process and their peers. Despite common difficulties of finding time for the sessions, clinical supervision can enhance collaboration and communication in the workplace. CONCLUSION: Clinical supervision that adheres to group rules can provide professional support within a safe, confidential space. Having trust in peers and facilitators at the sessions can help staff develop confidence, provide personal development and professional sustenance.

Very brief intervention for physical activity behaviour change in cardiac rehabilitation: protocol for the 'Measure It!' effectiveness-implementation hybrid trial.

INTRODUCTION: Physical inactivity is a risk factor for repeat cardiac events and all-cause mortality in coronary heart disease (CHD). Cardiac rehabilitation, a secondary prevention programme, aims to increase physical activity levels in this population from a reported low baseline. This trial will investigate the effectiveness and implementation of a very brief physical activity intervention, comparing different frequencies of physical activity measurement by cardiac rehabilitation clinicians. The Measure It! intervention (<5 min) includes a self-report and objective measure of physical activity (steps) plus very brief physical activity advice. METHODS AND ANALYSIS: This type 1 hybrid effectiveness-implementation study will use a two-arm multicentre assessor-blind randomised trial design. Insufficiently active (<150 min of moderate-to-vigorous physical activity per week) cardiac rehabilitation attendees with CHD (18+ years) will be recruited from five phase II cardiac rehabilitation centres (n=190). Patients will be randomised (1:1) to five physical activity measurements or two physical activity measurements in total over 24 weeks. The primary effectiveness outcome is accelerometer daily minutes of moderate-to-vigorous intensity physical activity at 24 weeks. Secondary effectiveness outcomes include body mass index, waist circumference and quality-of-life. An understanding of multilevel contextual factors that influence implementation, and antecedent outcomes to implementation of the intervention (eg, feasibility and acceptability), will be obtained using semistructured interviews and other data sources. Linear mixed-effects models will be used to analyse effectiveness outcomes. Qualitative data will be thematically analysed inductively and deductively using framework analysis, with the framework guided by the Consolidated Framework for Implementation Research and Theoretical Domains Framework. ETHICS AND DISSEMINATION: The study has ethical approval (University of Canberra (ID 11836), Calvary Bruce Public Hospital (ID 14-2022) and the Greater Western Area (ID 2022/ETH01381) Human Research Ethics Committees). Results will be disseminated in multiple formats for consumer, public and clinical audiences. TRIAL REGISTRATION NUMBER: ACTRN12622001187730p.

Testing the Effect of a Smartphone App on Hospital Admissions and Sedentary Behavior in Cardiac Rehabilitation Participants: ToDo-CR Randomized Controlled Trial.

BACKGROUND: People with coronary heart disease are at an increased risk of morbidity and mortality even if they attend cardiac rehabilitation. High sedentary behavior levels potentially contribute to this morbidity. Smartphone apps may be feasible to facilitate sedentary behavior reductions and lead to reduced health care use. OBJECTIVE: We aimed to test the effect of a sedentary behavior change smartphone app (Vire app and ToDo-CR program) as an adjunct to cardiac rehabilitation on hospital admissions and emergency department (ED) presentations over 12 months. METHODS: A multicenter, randomized controlled trial was conducted with 120 participants recruited from 3 cardiac rehabilitation programs. Participants were randomized 1:1 to cardiac rehabilitation plus the fully automated 6-month Vire app and ToDo-CR program (intervention) or usual care (control). The primary outcome was nonelective hospital admissions and ED presentations over 12 months. Secondary outcomes including accelerometer-measured sedentary behavior, BMI, waist circumference, and quality of life were recorded at baseline and 6 and 12 months. Logistic regression models were used to analyze the primary outcome, and linear mixed-effects models were used to analyze secondary outcomes. Data on intervention and hospital admission costs were collected, and the incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Participants were, on average, aged 62 (SD 10) years, and the majority were male (93/120, 77.5%). The intervention group were more likely to experience all-cause (odds ratio [OR] 1.54, 95% CI 0.58-4.10; P=.39) and cardiac-related (OR 3.26, 95% CI 0.84-12.55; P=.09) hospital admissions and ED presentations (OR 2.07, 95% CI 0.89-4.77; P=.09) than the control group. Despite this, cardiac-related hospital admission costs were lower in the intervention group over 12 months (Aus $252.40 vs Aus $859.38; P=.24; a currency exchange rate of Aus $1=US $0.69 is applicable). There were no significant between-group differences in sedentary behavior minutes per day over 12 months, although the intervention group completed 22 minutes less than the control group (95% CI -22.80 to 66.69; P=.33; Cohen d=0.21). The intervention group had a lower BMI (ß=1.62; P=.05), waist circumference (ß=5.81; P=.01), waist-to-hip ratio (ß=.03, P=.03), and quality of life (ß=3.30; P=.05) than the control group. The intervention was more effective but more costly in reducing sedentary behavior (ICER Aus $351.77) and anxiety (ICER Aus $10,987.71) at 12 months. The intervention was also more effective yet costly in increasing quality of life (ICER Aus $93,395.50) at 12 months. CONCLUSIONS: The Vire app and ToDo-CR program was not an outcome-effective or cost-effective solution to reduce all-cause hospital admissions or ED presentations in cardiac rehabilitation compared with usual care. Smartphone apps that target sedentary behavior alone may not be an effective solution for cardiac rehabilitation participants to reduce hospital admissions and sedentary behavior. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12619001223123; https://australianclinicaltrials.gov.au/anzctr/trial/ACTRN12619001223123. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-040479.

The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.

PURPOSE OF REVIEW: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models. RECENT FINDINGS: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Impact of on-site pharmacists in residential aged care facilities on the quality of medicines use: a cluster randomised controlled trial (PiRACF study).

Residents of residential aged care facilities (RACFs) have a high prevalence of use of potentially inappropriate medications (PIMs) and resultant medicines-related harm. This study investigated the effect of an on-site pharmacist model on PIMs use and other medication outcomes for residents in RACFs. A multi-facility, non-blind, cluster randomised controlled trial, with randomisation at the facility level, was conducted. Fifteen facilities enrolled and participated in the study, 7 facilities (560 residents) were allocated to the intervention arm and 8 facilities (737 residents) were allocated to the control arm. Each facility in the intervention arm employed an on-site pharmacist for 12 months to perform medication management activities as part of an interdisciplinary care team. The primary outcome was the proportion of residents taking at least one PIM according to the 2019 Beers® Criteria. Using generalised linear mixed-effects models, accounting for confounders and clustering, there was a significant reduction in the proportion of residents prescribed at least one PIM (odds ratio 0.50, 95% confidence interval, 0.335-0.750; p = 0.001) in the intervention arm. There were also significant decreases in the Anticholinergic Cognitive Burden scale and chlorpromazine equivalent daily dose of antipsychotics. The on-site pharmacist intervention significantly improved the appropriateness of medicines use in RACFs.

The role of on-site pharmacist in residential aged care facilities: findings from the PiRACF study.

BACKGROUND: Residents in residential aged care facilities (RACFs) have a high number of medication-related problems. Integrating on-site pharmacists (OSPs) into this setting is a possible solution and is currently gaining traction in Australia and internationally. The Pharmacists in Residential Aged Care Facilities (PiRACF) cluster-randomised controlled trial integrated pharmacists into the RACF care team to improve medication management. The aim of this descriptive observational study is to explore the activities of OSPs when they are integrated into multidisciplinary care team in RACFs. METHOD: An online survey tool was developed to record the activities of OSPs in RACFs using the Qualtrics© software. OSPs were asked questions about their activities in RACFs under categories that included description, time spent, outcomes where applicable and who the pharmacists communicated with to undertake the activity. RESULTS: Six pharmacists were integrated into 7 RACFs. Overall, they recorded 4252 activities over 12 months. OSPs conducted 1022 (24.0%) clinical medication reviews; 48.8% of medication reviews identified and discussed potentially inappropriate medications with prescribers and 1025 other recommendations were made to prescribers. Overall, the prescriber accepted 51.5% of all recommendations made by OSPs. The most frequently accepted outcome was deprescribing of medications (47.5% for potentially inappropriate medications and 55.5% for other recommendations). OSPs performed facility-level activities including staff education (13.4%), clinical audits (5.8%), and quality improvement activities (9.4%). OSPs spent a large proportion of their time communicating (23.4%) extensively with prescribers, RACF's healthcare team, and residents. CONCLUSION: OSPs successfully performed a wide range of clinical activities aimed both at improving residents' medication regimens, and organisational-level quality improvement. The OSP model presents an opportunity for pharmacists to enhance medication management in the residential aged care setting. Trial registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN: ACTRN12620000430932) on April 1, 2020.

Enjoyed by Jack but Endured by Jill: An Exploratory Case Study Examining Differences in Adolescent Design Preferences and Perceived Impacts of a Secondary Schoolyard.

The school grounds provide students opportunities for respite, relaxation and relief from daily stresses during breaks in the school day. However, it is unclear whether secondary schoolyard designs adequately support the diverse and evolving needs of adolescents, particularly at a time when they are experiencing rapid emotional and physical developmental change. To investigate this, quantitative methods were used to explore differences in perceptions of schoolyard attractiveness and restorative quality based on student gender and year level. A school-wide survey was administered to approximately 284 students in years 7 to 10 at a secondary school in Canberra, Australia. Results indicate significant declines in student perceptions of schoolyard attractiveness and restorative quality. Higher ratings of schoolyard likeability, accessibility, personal connection and restorative quality of 'being away' were associated with male students across all year levels. Further work is needed to explore how schoolyard environments can better support the design preferences and well-being needs of older and female students. Such information would help planners, designers and land managers develop schoolyard designs that are more equitable in their benefits to secondary school students of different genders and year levels.

L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress.

Lactoferrin (LF) is a multifunctional antimicrobial, anti-inflammatory, and antioxidant protein that occurs naturally in mammals, most notably in exocrine gland tissues and fluids, such as in the eye. Nitrosative stress can promote changes to tyrosine and other amino acid residues of the protein, which also reduces the activity of LF. l-ergothioneine (ET) is a potent anti-inflammatory antioxidant present in the eye and other tissues through nutrition or supplementation and that may play a role in the prevention or treatment of a variety of diseases. Here we investigated the ability of ET to reduce 3-nitrotyrosine (NTyr) formation using two separate substrates, with the goal of determining whether ET can protect the antibacterial function of LF and other proteins when exposed separately to peroxynitrite and tetranitromethane as nitrating reagents. Native human LF was used as a simple protein substrate, and lamb corneal lysate was chosen as one example of mammalian tissue with a more complex mixture of proteins and other biomolecules. Nitration was monitored by absorbance and fluorescence spectroscopy as well as sandwich (nitrated LF) and direct NTyr (corneal lysate) enzyme-linked immunosorbent assays (ELISAs). We found that pretreatment with ET reduced chemical modification of both native LF and corneal lysate samples and loss of antibacterial LF function due to exposure to the nitrating reagents. These initial results suggest that ET, raised to sufficiently elevated levels, could be tailored as a therapeutic agent to reduce effects of nitrosative stress on LF and in turn sustain the protein activity.

Engaging participants with research findings: A rights-informed approach.

BACKGROUND: Sharing research findings with participants is recognized as an ethical imperative for the research community. However, most discourse on this topic in mainstream public health takes a paternalistic approach, with researchers retaining the power to choose if, when, and how research findings are shared. METHODS: Fieldwork took place from August 2018 to January 2019 and again from August 2019 to December 2019 among two communities in the south Indian state of Kerala. We integrated participant engagement with study findings into the research protocol, using various collaborative strategies identified during the design stage, forming partnerships with participants and determining appropriate forms of dissemination for different participant groups during fieldwork. RESULTS: Findings from previous research projects undertaken with these communities by other researchers had not been shared with them. This was interpreted by the communities as researchers not being interested in making a difference to their situation. In the current study, building reciprocal relationships that minimized power disparities, and providing outputs in tailored formats that promoted active engagement were key factors that enabled participants to engage with results. This engagement added value by enabling us to co-develop study recommendations. This process also enabled the community to have ownership of the results and use them to advocate for health system change to improve access to health care. CONCLUSION: Research should be transformative for participating communities. Participants have a right to know the results of the research they participate in since their knowledge provides the research data which can in turn promote community change. Operationalising this requires researchers to build partnerships with participants and their communities from the outset. The role of participants must be reimagined, and adequate resources should be built into the research process. This is both socially responsible and ethical, but also improves the impact and legitimacy of research for the participants and the communities that they represent. PATIENT OR PUBLIC CONTRIBUTION: Participants of our research contributed to the design of various aspects of the engagement processes including the venue, the formats used for engagement, interpretation of the findings and recommendations from our research.

Cardiovascular Rehabilitation for transient ischaemic Attack and Mild Stroke: the CRAMS effectiveness-implementation hybrid study protocol.

BACKGROUND: Internationally, stroke and cardiac rehabilitation clinicians agree that current cardiac rehabilitation models are a suitable secondary prevention program for people following a transient ischaemic attack (TIA) or mild stroke. There is strong evidence for exercise-based cardiac rehabilitation in people with heart disease, however, the evidence for cardiac rehabilitation post-TIA or stroke is limited. Here we will explore the effectiveness and implementation of an integrated (TIA, mild stroke, heart disease) traditional exercise-based cardiovascular rehabilitation (CVR) program for people with TIA or mild stroke over 6-months. METHODS: This type 1 effectiveness-implementation hybrid study will use a 2-arm single-centre assessor-blind randomised controlled trial design, recruiting 140 participants. Adults who have had a TIA or mild stroke in the last 12-months will be recruited by health professionals from hospital and primary healthcare services. Participants will be assessed and randomly allocated (1:1) to the 6-week CVR program or the usual care 6-month wait-list control group. Distance completed in the 6-min walk test will be the primary effectiveness outcome, with outcomes collected at baseline, 6-weeks (complete CVR) and 6-months in both groups. Other effectiveness outcome measures include unplanned cardiovascular disease-related emergency department and hospital admissions, daily minutes of accelerometer moderate-to-vigorous physical activity, body mass index, waist circumference, blood pressure, quality of life, anxiety and depression. Implementation outcomes will be assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, including a cost-effectiveness analysis. Semi-structured interviews will be conducted with participants and CVR program health professionals, investigating the acceptability, value, and impact of the CVR program. Qualitative analyses will be guided by the Consolidated Framework for Implementation Research. DISCUSSION: Few studies have assessed the effectiveness of cardiac rehabilitation for people with TIA and mild stroke, and no studies appear to have investigated the cost-effectiveness or implementation determinants of such programs. If successful, the CVR program will improve health outcomes and quality of life of people who have had a TIA or mild stroke, guiding future research, policy, and clinical practice, reducing the risk of repeat heart attacks and strokes for this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621001586808 , Registered 19 November 2021.

A20 controls RANK-dependent osteoclast formation and bone physiology.

The anti-inflammatory protein A20 serves as a critical brake on NF-κB signaling and NF-κB-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been associated with several inflammatory disorders, including rheumatoid arthritis (RA), and experimental studies in mice have demonstrated that myeloid-specific A20 deficiency causes the development of a severe polyarthritis resembling human RA. Myeloid A20 deficiency also promotes osteoclastogenesis in mice, suggesting a role for A20 in the regulation of osteoclast differentiation and bone formation. We show here that osteoclast-specific A20 knockout mice develop severe osteoporosis, but not inflammatory arthritis. In vitro, osteoclast precursor cells from A20 deficient mice are hyper-responsive to RANKL-induced osteoclastogenesis. Mechanistically, we show that A20 is recruited to the RANK receptor complex within minutes of ligand binding, where it restrains NF-κB activation independently of its deubiquitinating activity but through its zinc finger (ZnF) 4 and 7 ubiquitin-binding functions. Together, these data demonstrate that A20 acts as a regulator of RANK-induced NF-κB signaling to control osteoclast differentiation, assuring proper bone development and turnover.

Association of device-measured physical activity and sedentary behaviour with cardiovascular risk factors, health-related quality-of-life and exercise capacity over 12-months in cardiac rehabilitation attendees with coronary heart disease.

BACKGROUND: Few studies have considered the relationship between risk factors, physical activity and sedentary behaviour in people with heart disease. Here we examine the independent relationship of device-measured physical activity and sedentary behaviour on risk factors, quality-of-life and exercise capacity over 12-months in cardiac rehabilitation attendees. METHODS: Hospital-based phase II cardiac rehabilitation participants with coronary heart disease were assessed at the start and end of cardiac rehabilitation (6-weeks), 6 and 12-months. Physical activity (moderate-to-vigorous (MVPA), light-intensity (LIPA); min/day) and sedentary behaviour (min/day, bouts, breaks) were measured using an ActiGraph accelerometer. Risk factors included waist circumference, body mass index, systolic blood pressure (SBP), fasting blood lipid and glucose levels, anxiety and depression. Quality-of-life and exercise capacity were also collected. Associations were assessed with Generalized Estimating Equation modeling. RESULTS: Sixty-seven participants were included (mean age = 64 (SD 9) years; 81% male). An association was found between higher MVPA and lower high density lipoprotein (p ≤ 0.001). No significant (p ≤ 0.001) associations were found between sedentary behaviour variables and other outcomes. At p < 0.05 several associations were significant. Increased MVPA and LIPA were associated with decreased total cholesterol. Higher MVPA was associated with decreased SBP, whereas higher LIPA was associated with decreased waist circumference and body mass index. Higher sedentary behaviour bouts and breaks were associated with increased total cholesterol, anxiety and depression, and decreased SBP over time. CONCLUSIONS: Any intensity of physical activity was associated with decreased total cholesterol. Increased LIPA was associated with improved measures of adiposity, while breaking up sedentary behaviour and increasing MVPA may decrease SBP over time. Further investigation of MVPA, LIPA and the distribution of sedentary behaviour is indicated in cardiac rehabilitation attendees to explore their relationship with risk factors. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12615000995572, http://www.ANZCTR.org.au/ACTRN12615000995572.aspx . Registered 22 September 2015.

Quality Use of Medicines Indicators and Associated Factors in Residential Aged Care Facilities: Baseline Findings from the Pharmacists in RACF Study in Australia.

Prescribing potentially inappropriate medications (PIMs), including antipsychotics and benzodiazepines, has been used as an indicator of the quality use of medicines in residential aged care facilities (RACFs). PIMs are associated with an increased risk of falls and hospitalisations in the elderly. The purpose of this study is to assess the extent of prescribing of PIMs in RACFs at baseline in the Pharmacists in residential aged care facilities (PiRACF) study and examine the association of resident and system factors with the number of PIMs. A cross-sectional analysis of 1368 participants from 15 Australian RACFs was performed to detect PIMs using the American Geriatrics Society 2019 Beers® criteria. Most residents (68.1%) were taking at least one regular PIM; 16.9% were taking regular antipsychotics and 11.1% were taking regular benzodiazepines. Long-term proton pump inhibitors were the most frequent class of PIMs. History of falls and higher Charlson Comorbidity Index were associated with an increased number of prescribed PIMs, while dementia diagnosis and older age (85 years or more) were associated with decreased number of PIMs (p-value <0.05). Residents in facilities with lower nurse-to-resident ratios were more likely to have an increased number of PIMs (p value = 0.001). This study indicates that potentially inappropriate prescribing is common in RACFs and interventions to target residents at highest risk are needed.

A Good start in life: Effectiveness of integrated multicomponent multisector support on early child development-Study protocol.

INTRODUCTION: Early childhood experiences have a lifelong impact on a child's future. Social and environmental experiences and interactions have a profound relational effect on children's physical and mental health which transfers agency to parents, caregivers and duty-bearers to care for the child's welfare. In the Australian context early child development indices have been in decline in some communities. Hence, there is a sense of urgency to reverse these trends from an integrated perspective. A multisector, multi component program of interventions named A Good Start in Life is proposed and is being tested in the Australian Capital Territory across suburbs with high levels of early childhood development disadvantage. The aim of this study is to evaluate the outcomes and processes related to targeted interventions, designed to integrate child and family services within the local district and embed allied health programs into early childhood education, care services and playgroups. METHODS AND ANALYSIS: The Good Start in Life study will use a quasi-experimental design (with a matched control geographical area) consisting of a combination of interventions that will build multisectoral collaboration across education, health and social services that connect and support families with children from birth to 5 years. The control area will be matched on demographic characteristics and early child development outcomes and trends over the pre-intervention period. Evaluation data will be collected at baseline, and then on an annual basis for a further three years. A mixed methods approach will be used to evaluate delivery processes: quantitative (checklists, questionnaires) and qualitative methods (observations, focus groups and key stakeholder interviews). Effectiveness of the programme will be evaluated by comparing early child development outcomes between the comparator areas from the Australian Early Development Census in 2024. The primary focus will be on reducing the number of children who are developmentally vulnerable on at least one early development index (EDI). Separate tests will be conducted for significant differences in the percentage of children at risk in each of the five individual EDI domains. These domains are physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, and communication and general knowledge. TRIAL REGISTRATION: ACTRN12621001140842.

Behaviour change techniques in cardiovascular disease smartphone apps to improve physical activity and sedentary behaviour: Systematic review and meta-regression.

BACKGROUND: Smartphone apps are increasingly used to deliver physical activity and sedentary behaviour interventions for people with cardiovascular disease. However, the active components of these interventions which aim to change behaviours are unclear. AIMS: To identify behaviour change techniques used in smartphone app interventions for improving physical activity and sedentary behaviour in people with cardiovascular disease. Secondly, to investigate the association of the identified techniques on improving these behaviours. METHODS: Six databases (Medline, CINAHL Plus, Cochrane Library, SCOPUS, Sports Discus, EMBASE) were searched from 2007 to October 2020. Eligible studies used a smartphone app intervention for people with cardiovascular disease and reported a physical activity and/or sedentary behaviour outcome. The behaviour change techniques used within the apps for physical activity and/or sedentary behaviour were coded using the Behaviour Change Technique Taxonomy (v1). The association of behaviour change techniques on physical activity outcomes were explored through meta-regression. RESULTS: Forty behaviour change techniques were identified across the 19 included app-based interventions. Only two studies reported the behaviour change techniques used to target sedentary behaviour change. The most frequently used techniques for sedentary behaviour and physical activity were habit reversal and self-monitoring of behaviour respectively. In univariable analyses, action planning (ß =0.42, 90%CrI 0.07-0.78) and graded tasks (ß =0.33, 90%CrI -0.04-0.67) each had medium positive associations with increasing physical activity. Participants in interventions that used either self-monitoring outcome(s) of behaviour (i.e. outcomes other than physical activity) (ß = - 0.47, 90%CrI -0.79--0.16), biofeedback (ß = - 0.47, 90%CrI -0.81--0.15) and information about health consequences (ß = - 0.42, 90%CrI -0.74--0.07) as behaviour change techniques, appeared to do less physical activity. In the multivariable model, these predictors were not clearly removed from zero. CONCLUSION: The behaviour change techniques action planning and graded tasks are good candidates for causal testing in future experimental smartphone app designs.