Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia.

Background: Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR1. In this first-in-human study, icanbelimod was investigated in healthy men in Australia. Methods: Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort. Results: Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (Tmax 4-7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions. Conclusion: Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts. Clinical trial registration: ClinicalTrials.gov, identifier NCT02280434.b.

Improving the identification of bone-specific physical activity using wrist-worn accelerometry: A cross-sectional study in 11-12-year-old Australian children.

Physical activity (PA) during childhood and adolescence is important for the accrual of maximal peak bone mass. The precise dose that benefits bone remains unclear as methods commonly used to analyze PA data are unsuitable for measuring bone-relevant PA. Using improved accelerometry methods, this study identified the amount and intensity of PA most strongly associated with bone outcomes in 11-12-year-olds. Participants (n = 770; 382 boys) underwent tibial peripheral quantitative computed tomography to assess trabecular and cortical density, endosteal and periosteal circumference and polar stress-strain index. Seven-day wrist-worn raw acceleration data averaged over 1-s epochs was used to estimate time accumulated above incremental PA intensities (50 milli-gravitational unit (mg) increments from 200 to 3000 mg). Associations between time spent above each 50 mg increment and bone outcomes were assessed using multiple linear regression, adjusted for age, sex, height, weight, maturity, socioeconomic position, muscle cross-sectional area and PA below the intensity of interest. There was a gradual increase in mean R2 change across all bone-related outcomes as the intensity increased in 50 mg increments from >200 to >700 mg. All outcomes became significant at >700 mg (R2 change = 0.6%-1.3% and p = 0.001-0.02). Any further increases in intensity led to a reduction in mean R2 change and associations became non-significant for all outcomes >1500 mg. Using more appropriate accelerometry methods (1-s epochs; no a priori application of traditional cut-points) enabled us to identify that ∼10 min/day of PA >700 mg (equivalent to running ∼10 km/h) was positively associated with pQCT-derived measures of bone density, geometry and strength in 11-12-year-olds.

Injections in the back of the eye: The why, the what and when to worry.

BACKGROUND: Many Australians, particularly the elderly, suffer from eye diseases that require treatment with regular injections given into the eye. These injections can result in complications, some of which can be vision threatening. OBJECTIVE: To summarise some of the more common reasons for intraocular injection, as well as some common and/or more serious complications of intraocular injection that might present to general practitioners. DISCUSSION: Intraocular injection is an increasingly common means of treatment for a range of eye conditions. Serious complications, although rare, often require acute intervention to achieve the best outcomes, and timely referral of patients with worrying symptoms is important to achieve optimum patient care.

An innovative business model using established Medicare items for delivery of cardiac rehabilitation: A value proposition for primary care.

BACKGROUND: Approximately 70% of Australians do not attend cardiac rehabilitation (CR). A potential solution is integrating CR into primary care OBJECTIVE: To propose a business model for primary care providers to implement CR using current Medicare items. DISCUSSION: Using the chronic disease management plan, general practitioners (GPs) complete four clinical assessments at 1-2 weeks, 8-12 weeks, and 6 and 12 months after discharge. The net benefit of applying this model, compared with claiming the most used standard consultation Item 23, in Phase II CR is up to $505 per patient and $543 in Phase III CR. The number of rural GPs providing CR in partnership with the Country Access To Cardiac Health (CATCH) through the GP hybrid model has increased from 28 in 2021 to 32 in 2022. This increase might be attributed to this value proposition. The biggest limitation is access to allied health services in the rural areas.

Ageing with chronic conditions and older persons' experience of social connections: a qualitative descriptive study.

Background Chronic conditions may limit older peoples' social engagement and wellbeing. Reduced social connections can result in loneliness and social isolation. This study aimed to explore the experience of social connection in older people living with chronic conditions, and the factors influencing their social participation. Methods A purposive sample of 19 community-dwelling older Australians (mean age 75.5years) with one or more chronic conditions participated in a qualitative descriptive study. Semi-structured interviews explored participants' perceptions of their social connections and the potential impact of their chronic conditions. Views about the role of general practice in supporting older persons' wellbeing were discussed. Data were analysed inductively using thematic analysis. Results Five themes were identified: (1) the experience of loneliness, (2) managing diminishing social contacts, (3) living with chronic conditions, (4) barriers to social connection, and (5) facilitators of social connection. Participants felt that ageing with chronic conditions contributed to loss of function and independence, which limited social connections, and increased loneliness and social isolation. Barriers to social connections included issues with mobility, transport and forming new networks. Families were a primary support, with continued community engagement and general practice support crucial to staying well and socially connected. Conclusions Understanding older peoples' experiences, and the barriers and facilitators of social connections can guide clinicians' interventions. General practice is a promising intervention point because of its high use by those with chronic conditions to stay well. General practice nurses are well-placed to collaboratively address the barriers older people face in maintaining social connections.

Outbreak of Ralstonia pickettii associated with contamination of saline products distributed internationally, the United Kingdom, 2024.

We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.

'It's Just Not Working', a Qualitative Exploration of the Weight-Related Healthcare Experiences of Individuals of Arab Heritage With Higher Weight in Australia.

INTRODUCTION: Culturally and linguistically diverse population groups disproportionately experience higher weight and other non-weight-related discrimination in healthcare settings outside of their ancestral country. Little is known about the experiences of individuals with Arab heritage. This study aimed to qualitatively explore the intersectional weight-related healthcare experiences of individuals of Arab heritage with higher weight in Australia. METHODS: A general inductive enquiry approach was used. Purposive, convenience and snowball sampling was used to recruit individuals of Arab heritage residing in Australia. Individuals were invited to participate in an online semistructured interview. Interviews were recorded, transcribed and thematically analysed. RESULTS: Fifteen participants took part in the study. Of these participants, 93% were female (n = 14), 80% were aged between 18 and 44 years (n = 12), 73% were university educated (n = 11), 53% were born outside of Australia (n = 8) and all were Muslim (n = 15). Four main themes were identified: (1) appearance-based judgement, (2) generalised advice and assumptions, (3) cultural responsiveness and (4) healthcare system constraints. CONCLUSION: Individuals of Arab heritage with higher weight in Australia, namely, females, often perceive their healthcare experiences as dismissive of their cultural and religious needs and driven by causality assumptions around weight. It is crucial that care delivered encompasses cultural humility, is weight-inclusive and acknowledges systemic constraints. Cultural safety training benchmarks, healthcare management reform and weight-inclusive healthcare approaches are recommended to assist healthcare providers in delivering effective, holistic and culturally safe care. PATIENT OR PUBLIC CONTRIBUTION: Insights gained from conversations with Arab heritage community members with lived experiences regarding weight-related healthcare encounters informed the study design and approach.

Eye and adnexa hospitalization in Australia: An ecological study.

To investigate the trends of hospital admissions concerning diseases of the eye and adnexa in Australia in the past 2 decades. This is a descriptive ecological study on the population level that examined hospitalization data for the duration between 1998 and 2021 in Australia. Hospitalization data were extracted from the National Hospital Morbidity Database. The chi-squared test was utilized to assess the difference in admission rates between the years 1998 and 2021. Hospital admission rate for diseases of the eye and adnexa increased by 1.20-fold (from 852.32 [95% confidence interval [CI] 848.16-856.47] in 1998 to 1873.72 [95% CI 1868.48-1878.96] in 2021 per 100,000 persons, P < .01). The most common cause of hospitalization for diseases of the eye and adnexa was disorders of the lens (65.7%), followed by disorders of the choroid and retina (15.6%), followed by disorders of the eyelid, lacrimal system, and orbit (7.7%). Hospital admission rate among males increased by 1.25-fold (from 737.67 [95% CI 732.18-743.16] in 1998 to 1657.19 [95% CI 1650.19-1664.20] in 2021 per 100,000 persons). Hospital admission rate among females increased less sharply by 1.03-fold (from 965.37 [95% CI 959.14-971.59] in 1998 to 1964.35 [95% CI 1956.80-1971.90] in 2021 per 100,000 persons). There are clear gender and age roles in the epidemiology of hospital admissions related to eye and adnexa disorders. Lens disorders were the most common cause of hospital admission. The admission rate increase during the past decades could be due to increases in life expectancy, lifestyle changes, and improvements in screening protocols.

Ngulluk Moort, Ngulluk Boodja, Ngulluk Wirin (our family, our country, our spirit): An Aboriginal Participatory Action Research study protocol.

Globally, Indigenous children have historical and contemporary connections with government child protection services that have caused significant harm to their long-term health and wellbeing. Innovative, culturally secure and recovery focussed service provision is required. This paper describes a research protocol that has been designed by Indigenous researchers led by Indigenous Elders, to explore culturally secure care planning and service delivery in out-of-home care agencies in Australia. Using participatory action research methods, we will collect data using a variety of forums, including focus groups and semi-structured interviews. These data will explore the challenges for out-of-home care agencies in providing culturally secure care-planning, cultural activity and resources, and explore solutions to address factors that influence health and can assist to redress social inequities for Indigenous children. We aim to recruit approximately 100 participants for the qualitative study and 40 participants for the quantitative survey. Study participants will initially be recruited using purposive sampling, and as the study progresses will be recruited using a mixture of purposive and convenience sampling techniques. The rich data that this study is expected to yield, will inform ways to collect cultural information about Indigenous children and ways to provide cultural connections and activities that will have benefit to Indigenous children and families, and a broad range of social services.

Diagnosing and managing prescription opioid use disorder in patients prescribed opioids for chronic pain in Australian general practice settings: a qualitative study using the theory of Planned Behaviour.

BACKGROUND: Chronic pain is a debilitating and common health issue. General Practitioners (GPs) often prescribe opioids to treat chronic pain, despite limited evidence of benefit and increasing evidence of harms, including prescription Opioid Use Disorder (pOUD). Australian GPs are worried about the harms of long-term opioids, but few are involved in the treatment of pOUD. There is little research on GPs' experiences diagnosing and managing pOUD in their chronic pain patients. METHODS: This qualitative research used semi-structured interviews and a case study to investigate GPs' experiences through the lens of the Theory of Planned Behaviour (TPB). TPB describes three factors, an individual's perceived beliefs/attitudes, perceived social norms and perceived behavioural controls. Participants were interviewed via an online video conferencing platform. Interviews were transcribed verbatim and thematically analysed. RESULTS: Twenty-four GPs took part. Participants were aware of the complex presentations for chronic pain patients and concerned about long-term opioid use. Their approach was holistic, but they had limited understanding of pOUD diagnosis and suggested that pOUD had only one treatment: Opioid Agonist Treatment (OAT). Participants felt uncomfortable prescribing opioids and were fearful of difficult, conflictual conversations with patients about the possibility of pOUD. This led to avoidance and negative attitudes towards diagnosing pOUD. There were few positive social norms, few colleagues diagnosed or managed pOUD. Participants reported that their colleagues only offered positive support as this would allow them to avoid managing pOUD themselves, while patients and other staff were often unsupportive. Negative behavioural controls were common with low levels of knowledge, skill, professional supports, inadequate time and remuneration described by many participants. They felt OAT was not core general practice and required specialist management. This dichotomous approach was reflected in their views that the health system only supported treatment for chronic pain or pOUD, not both conditions. CONCLUSIONS: Negative beliefs, negative social norms and negative behavioural controls decreased individual behavioural intention for this group of GPs. Diagnosing and managing pOUD in chronic pain patients prescribed opioids was perceived as difficult and unsupported. Interventions to change behaviour must address negative perceptions in order to lead to more positive intentions to engage in the management of pOUD.

Retrospective audit compares screening and treatment of pregnancy-related anaemia in regional New South Wales with Australian guidelines.

BACKGROUND: Anaemia during pregnancy is common worldwide. In Australia, approximately 17% of non-pregnant women of reproductive age have anaemia, increasing to a rate of 25% in pregnant women. This study sought to determine the rate of screening for anaemia in pregnancy in regional New South Wales, and to determine whether screening and treatment protocols followed the recommended guidelines. METHODS: This retrospective study reviewed antenatal and postnatal (48 h) data of women (n = 150) who had a live birth at Bathurst Hospital between 01/01/2020 and 30/04/2020. Demographic data, risk factors for anaemia in pregnancy, antenatal bloods, treatments provided in trimesters one (T1), two (T2) and three (T3), and postpartum complications were recorded. These were compared to the Australian Red Cross Guidelines (ARCG) using descriptive statistics. RESULTS: Of the women with screening data available (n = 103), they were mostly aged 20-35yrs (79.6%), 23.3% were obese, 97.1% were iron deficient, 17% were anaemic and only a few (5.3%) completed the full pregnancy screening as recommended by the ARCG while a majority completed only partial screenings specifically Hb levels in T1 (56.7%), T2 (44.7%) and T3 (36.6%). Compliance to oral iron was largely undocumented, but constipation was a common side effect among the women. IV iron was administered in 14.0% of women, approximately 1.75x higher than the recommended rate. CONCLUSIONS: This study provided useful information about compliance to screening and treatment guidelines for anaemia in pregnancy. We identified the need for improved documentation and communication between various health providers to ensure adequate antenatal care to prevent maternal complications during pregnancy. This will improve patient care and encourage further developments in maternal care, bridging the rural health gap.

Actual Cost of Extracorporeal Cardiopulmonary Resuscitation: A Time-Driven Activity-Based Costing Study.

OBJECTIVES: To determine the actual cost and drivers of the cost of an extracorporeal cardiopulmonary resuscitation (E-CPR) care cycle. PERSPECTIVE: A time-driven activity-based costing study conducted from a healthcare provider perspective. SETTING: A quaternary care ICU providing around-the-clock E-CPR service for out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) in Australia. METHODS: The E-CPR care cycle was defined as the time from initiating E-CPR to hospital discharge or death of the patient. Detailed process maps with discrete steps and probabilistic decision nodes accounting for the complex trajectories of E-CPR patients were developed. Data about clinical and nonclinical resources and timing of activities was collected multiple times for each process . Total direct costs were calculated using the time estimates and unit costs per resource for all clinical and nonclinical resources. The total direct costs were combined with indirect costs to obtain the total cost of E-CPR. RESULTS: From 10 E-CPR care cycles observed during the study period, a minimum of 3 observations were obtained per process. The E-CPR care cycle's mean (95% CI) cost was $75,014 ($66,209-83,222). Initiation of extracorporeal membrane oxygenation (ECMO) and ECMO management constituted 18% of costs. The ICU management (35%) and surgical costs (20%) were the primary cost determinants. IHCA had a higher mean (95% CI) cost than OHCA ($87,940 [75,372-100,570] vs. 62,595 [53,994-71,890], p < 0.01), mainly because of the increased survival and ICU length of stay of patients with IHCA. The mean cost for each E-CPR survivor was $129,503 ($112,422-147,224). CONCLUSIONS: Significant costs are associated with E-CPR for refractory cardiac arrest. The cost of E-CPR for IHCA was higher compared with the cost of E-CPR for OHCA. The major determinants of the E-CPR costs were ICU and surgical costs. These data can inform the cost-effectiveness analysis of E-CPR in the future.

Towards precision cancer medicine for Aboriginal and Torres Strait Islander cancer health equity.

Delivering cancer control at scale for Aboriginal and Torres Strait Islander communities is a national priority that requires Aboriginal and Torres Strait Islander leadership and codesign, as well as significant involvement of the Aboriginal community-controlled health sector. The unique genomic variation observed among Aboriginal and Torres Strait Islander peoples may have implications for standard and precision medicine. Yet, Aboriginal and Torres Strait Islander peoples are absent from, or under-represented within, human reference genome resources, genomic studies, cancer studies, cancer cell lines, patient-derived xenografts and cancer clinical trials. Genomics-guided precision cancer medicine offers an opportunity to reduce cancer health disparities experienced by Aboriginal and Torres Strait Islander peoples through personalising prevention, diagnosis, treatment and long term management. Here, we describe what is required to ensure that Aboriginal and Torres Strait Islander peoples can receive the benefits of precision cancer medicine. Equity of access to care, an Aboriginal and Torres Strait Islander cancer workforce, and appropriate genome reference resources are important for safe and effective cancer medicine. Building Indigenous data sovereignty principles and Aboriginal and Torres Strait Islander governance into research is required to protect Aboriginal and Torres Strait Islander rights and collective interests. Aboriginal and Torres Strait Islander community engagement should be undertaken to develop an understanding of the unique cultural and ethical considerations for precision cancer research. Local and national genomic health research guidelines are needed to define a consensus best practice in genomics research with Aboriginal and Torres Strait Islander peoples.

Aged care service use by Aboriginal and Torres Strait Islander people after aged care eligibility assessments, 2017-2019: a population-based retrospective cohort study.

OBJECTIVE: To characterise the socio-demographic characteristics, aged and health care needs, and aged care services used by older Aboriginal and Torres Strait Islander people assessed for aged care service eligibility. STUDY DESIGN: Population-based retrospective cohort study; analysis of Registry of Senior Australians (ROSA) National Historical Cohort data. SETTING, PARTICIPANTS: Aboriginal and Torres Strait Islander people aged 50 years or older who were first assessed for aged care service eligibility (permanent residential aged care, home care package, respite care, or transition care) during 1 January 2017 - 31 December 2019. MAJOR OUTCOME MEASURES: Socio-demographic and aged care assessment characteristics; health conditions and functional limitations recorded at the time of the assessment; subsequent aged care service use. RESULTS: The median age of the 6209 people assessed for aged care service eligibility was 67 years (interquartile range [IQR], 60-75 years), 3626 were women (58.4%), and 4043 lived in regional to very remote areas of Australia (65.1%). Aboriginal health workers were involved in 655 eligibility assessments (10.5%). The median number of health conditions was six (IQR, 4-8); 6013 (96.9%) had two or more health conditions, and 2592 (41.8%) had seven or more. Comorbidity was most frequent among people with mental health conditions: 597 of 1136 people with anxiety (52.5%) and 1170 of 2416 people with depression (48.5%) had seven or more other medical conditions. Geriatric syndromes were recorded for 2265 people (36.5%); assistance with at least one functional activity was required by 6190 people (99.7%). A total of 6114 people (98.5%) were approved for at least one aged care service, 3218 of whom (52.6%) subsequently used these services; the first services used were most frequently home care packages (1660 people, 51.6%). CONCLUSION: Despite the high care needs of older Aboriginal and Torres Strait Islander people, only 52% used aged care services for which they were eligible. It is likely that the health and aged care needs of older Aboriginal and Torres Strait Islander people are not being adequately met.