High prevalence of diabetes among young First Nations Peoples with metabolic dysfunction-associated steatotic liver disease: a population-based study in Australia.

BACKGROUND: Liver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce. METHODS: A retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007-2019 in the state of Queensland was performed. Patients were followed from the first admission with MASLD/MASH (identified based on validated algorithms) to decompensated cirrhosis and overall mortality. We explored differences according to Indigenous status using Multivariable Cox regression. FINDINGS: 439 First Nations Peoples and 7,547 non-Indigenous Australians were followed for a median of 4.6 years (interquartile range 2.7-7.2). Overall, women were overrepresented, but more so in the First Nations cohort (72.7% vs. 57.0%, p < 0.001). First Nations patients were younger, a higher proportion lived in remote and socioeconomic disadvantaged areas, and had higher comorbidity compared to non-Indigenous Australians (all p < 0.001). Diabetes, the most common comorbidity affecting both groups, was overrepresented in First Nations Peoples versus non-Indigenous Australians (43.5% vs. 30.8%, p < 0.001, respectively). Nineteen (4.3%) First Nations Peoples and 332 (4.4%) of non-Indigenous patients progressed to cirrhosis decompensation (9.0% [95%CI 4.5-17.7] vs. 7.7% [95%CI 6.6-8.9; p = 0.956] respectively within 10 years). In multivariable analysis, there was no association between Indigenous status and progression to decompensated cirrhosis (p = 0.759) and survival (p = 0.437). CONCLUSIONS: This study provides the first population-based epidemiological data on MASLD in First Nations Australians. The high prevalence of diabetes (that is associated with advanced fibrosis and liver disease mortality) among young First Nations Peoples with MASLD raises concern about future risk of progressive liver disease in this patient population. These data highlight the importance of early identification of MASLD, and providing culturally appropriate intervention to reduce disease progression in parallel with the management of cardiometabolic comorbidities.

Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

BACKGROUND: Direct-acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow-up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real-world setting. METHODS: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016-2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health-care providers and re-treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. RESULTS: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child-Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj-OR = 2.82, 95% confidence interval [CI] 2.25-3.54), younger age (adj-OR = 2.63, 95% CI 1.80-3.84), Indigenous identification (adj-OR = 1.99, 95% CI 1.23-3.21), current injection drug use or opioid replacement therapy (adj-OR = 1.66, 95% CI 1.25-2.20), depression treatment (adj-OR = 1.49, 95% CI 1.17-1.90), and male gender (adj-OR = 1.31, 95% CI 1.04-1.66) were associated with LTFU. CONCLUSIONS: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV.

Changing Prevalence of Medication Use in People with Cirrhosis: A Retrospective Cohort Study Using Pharmaceutical Benefits Scheme Data.

BACKGROUND: Safe and appropriate use of medicines is essential to improve health outcomes in cirrhosis. However, little is known about the number and type of medicines dispensed to people with cirrhosis in Australia, as this predominantly occurs in the community. We aimed to characterise the prescriptions dispensed to people with cirrhosis and explore changes in the use of medication groups over time. METHODS: Pharmaceutical Benefits Scheme data between 1 January 2016 and 30 June 2020 was extracted for consenting CirCare participants (multi-site, prospective, observational study). Prescriptions dispensed from cirrhosis diagnosis until liver transplant or death were included. Safety classifications for dispensed medicines were defined using published evidence-based recommendations. The pattern of medication use was analysed in 6-monthly time intervals. Generalised estimating equations models were used to estimate the change in consumption of medicines over time. RESULTS: Five hundred twenty-two patients (mean age 60 years, 70% male, 34% decompensated at recruitment) were dispensed 89,615 prescriptions during the follow-up period, representing a median of 136 [interquartile range (IQR) 62-237] prescriptions and a median of 16 (IQR 11-23) unique medicines per patient (total n = 9306 medicines). The most commonly used medicines were proton pump inhibitors (PPIs) (dispensed at least once to 73% of patients), opioids (68%) and antibiotics (89%). Polypharmacy was prevalent, with 59-69% of observed participants in each time period dispensed five or more unique medicines. Prescription medication use increased over time (p < 0.001) independently of age, comorbidity burden and liver disease aetiology. The likelihood of taking PPIs, opioids, antidepressants and inhaled medicines also increased with each successive time period. Use of angiotensin therapies, metformin and statins differed over time between patients with compensated versus decompensated cirrhosis. General practitioners prescribed 69% of dispensed medicines, including a higher proportion of 'unsafe' and 'safety unknown' medicines compared with consultants/specialists (p < 0.001). CONCLUSIONS: Polypharmacy is common in people with cirrhosis and some medication groups may be overused. Pharmacovigilance is required and future medication safety efforts should target high-risk prescribing practices and promote medication rationalisation in the community.

Diabetes mellitus and the progression of non-alcoholic fatty liver disease to decompensated cirrhosis: a retrospective cohort study.

OBJECTIVE: To determine the incidence of decompensated cirrhosis and associated risk factors in people hospitalised with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) with or without cirrhosis. DESIGN: Retrospective cohort study; analysis of linked Queensland Hospital Admitted Patient Data Collection, Queensland Registry of Births, Deaths and Marriages, and Queensland Cancer Register data. SETTING, PARTICIPANTS: Queensland residents aged 20 years or older admitted to Queensland hospitals with NAFLD/NASH during 1 July 2009 - 31 December 2018. MAIN OUTCOME MEASURES: Progression to decompensated cirrhosis (ascites, hepatic encephalopathy, or oesophageal variceal bleeding). RESULTS: We included data for 8006 patients in our analysis (10 082 admissions), including 4632 women (58%) and 2514 people with diabetes mellitus (31%); median follow-up time was 4.6 years (interquartile range, 2.7-7.2 years). Three hundred and fifty-one people (4.4%) experienced decompensated cirrhosis during the follow-up period. Of the 6900 people without cirrhosis, 4.5% (95% confidence interval [CI], 3.6-5.7%) experienced decompensated cirrhosis within ten years (mean, 0.5% per year; 95% CI, 0.4-0.6% per year); risk of progression was greater for people aged 70 years or older (v 20-39 years: adjusted hazard ratio [aHR], 4.7; 95% CI, 2.0-11.0) and those who had extrahepatic cancers (aHR, 5.0; 95% CI, 3.0-8.2), history of major cardiovascular events (aHR, 1.9; 95% CI, 1.2-3.1), or diabetes mellitus (aHR, 2.8; 95% CI, 2.0-3.9). Of the 1106 people with cirrhosis, 32.4% (95% CI, 27.2-38.3%) experienced decompensated cirrhosis within ten years (mean, 5.5% per year; 95% CI, 4.8-6.3% per year); risk of progression was greater for those with portal hypertension (aHR, 1.8; 95% CI, 1.3-2.7), extrahepatic cancer (aHR, 1.8; 95% CI, 1.1-2.9), or diabetes mellitus (aHR, 1.5; 95% CI, 1.1-2.0). Compared with people who had neither cirrhosis nor diabetes mellitus, the risk of decompensation was greater for people with cirrhosis (aHR, 10.7; 95% CI, 7.6-15.0) or cirrhosis and diabetes mellitus (aHR, 14.4; 95% CI, 10.1-20.6). CONCLUSIONS: Given the greater risk of progression to cirrhosis decompensation in people with diabetes mellitus, a disorder common in people with NAFLD/NASH, identifying advanced fibrosis and providing appropriate treatment for averting disease progression is vital.

A discrete choice experiment to elicit preferences for a liver screening programme in Queensland, Australia: a mixed methods study to select attributes and levels.

BACKGROUND: In Australia, the overall prevalence of liver disease is increasing. Maximising uptake of community screening programmes by understanding patient preferences is integral to developing consumer-centred care models for liver disease. Discrete choice experiments (DCEs) are widely used to elicit preferences for various healthcare services. Attribute development is a vital component of a well-designed DCE and should be described in sufficient detail for others to assess the validity of outcomes. Hence, this study aimed to create a list of potential attributes and levels which can be used in a DCE study to elicit preferences for chronic liver disease screening programmes. METHODS: Key attributes were developed through a multi-stage, mixed methods design. Focus groups were held with consumers and health care providers on attributes of community screening programmes for liver disease. Stakeholders then prioritised attributes generated from the focus group in order of importance via an online prioritisation survey. The outcomes of the prioritisation exercise were then reviewed and refined by an expert panel to ensure clinically meaningful levels and relevance for a DCE survey. RESULTS: Fifteen attributes were generated during the focus group sessions deemed necessary to design liver disease screening services. Outcomes of the prioritisation exercise and expert panel stages recognised five attributes, with three levels each, for inclusion in a DCE survey to elicit consumer preferences for community screening for liver disease. This study also highlights broader social issues such as the stigma around liver disease that require careful consideration by policy makers when designing or implementing a liver screening programme. CONCLUSIONS: The attributes and levels identified will inform future DCE surveys to understand consumer preferences for community screening programmes for liver disease. In addition, the outcomes will help inform the implementation of the LOCATE-NAFLD programme in real-world practice, and could be relevant for other liver and non-liver related chronic disease screening programmes.

Lower prevalence of elevated liver stiffness measurements in people with type 2 diabetes taking sodium-glucose co-transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists.

INTRODUCTION AND OBJECTIVES: Among people with type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) is very common and has an increased risk of clinically significant liver disease. The use of sodium-glucose co-transporter 2 (SGLT2i) inhibitors and glucagon-like peptide-1 (GLP-1a) receptor agonists is endorsed to reduce major cardiovascular events and/or progression of chronic kidney disease. Their prevalence of use in people with T2D and co-existent NAFLD remains unclear. We sought to determine the prevalence of use of these medications at two different time periods, and their association with prevalence of clinically significant liver disease. MATERIALS AND METHODS: Consecutive people with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) were recruited from diabetes clinics between Jun-2021 and Jun-2022 ('current' cohort). Liver stiffness measurements (LSM) using FibroScan were performed. Medication data were collected prospectively at recruitment and verified with the dispensing pharmacy or general practitioner medical records. Data for a historical cohort with NAFLD and T2D recruited from the same clinics during 2015-2017 ('historical' cohort) were available. Logistic regression was used to evaluate factors associated with LSM <8.0 or ≥8 kPa (clinically significant fibrosis). RESULTS: There were 292 participants, 177 in the historical cohort and 115 in the current cohort. In the current cohort, 57.4% of patients with T2D and NAFLD were taking a GLP-1a and 42.6% were taking a SGLT2i; a 2.6 to 3.4-fold higher prevalence than in 2015-2017. A lower proportion of the current cohort (23.9% compared to 38.4%) had clinically significant fibrosis (LSM ≥8 kPa; p = 0.012). When the cohorts were pooled and differences adjusted for in multivariable logistic regression analysis, patients taking a GLP-1a or a SGLT2i were 2 times more likely to have a lower LSM (<8 kPa) compared to patients not taking these drugs (OR=2.05, 95%CI 1.07-3.94, p = 0.03 and OR 2.07 95%CI 1.04-4.11, p = 0.04, respectively). CONCLUSIONS: The observation of a lower LSM in people taking SGLT2i and/or GLP-1a following adjustment for other relevant clinico-demographic variables provides support for clinical trials to assess their efficacy in reducing the progression of NAFLD.

Low Prevalence of Use of Allied Health and Community Services for Patients with Cirrhosis in Australia: A Need for Greater Engagement.

Background: Psychosocial, lifestyle and practical needs are not routinely attended to during outpatient hepatology management, and little is known about the type and effectiveness of support services accessed by patients with cirrhosis. We quantified the type and use of community and allied health services in patients with cirrhosis. Methods: The study included 562 Australian adults with a diagnosis of cirrhosis. Health service use was assessed via questionnaire and via linkage to the Australian Medicare Benefits Schedule. Patient needs were assessed using the Supportive Needs Assessment tool for Cirrhosis (SNAC). Results: Although most patients (85.9%) used at least one community/allied health service for support with their liver disease, many reported requiring additional help with psychosocial (67.4%), lifestyle (34.3%) or practical needs (21.9%) that were not met by available services, or patients did not access services. A multidisciplinary care plan or case conference (in the 12 months prior to recruitment) was accessed by 48% of patients, 56.2% reported the use of a general practitioner for support with cirrhosis, and a dietician was the allied health clinician most accessed by patients (45.9%). Despite the high prevalence of psychosocial needs, there was relatively limited use of mental health and social work services (14.1% of patients reported the use of a psychologist), confirmed by a low prevalence of use of mental health services (17.7%) in the linked data. Conclusion: Patients with cirrhosis who have unmet complex physical and psychosocial needs require better strategies to increase their engagement with allied health and community services.

Higher levels of supportive care needs are linked to higher health service use and cost, poor quality of life, and high distress in patients with cirrhosis in Queensland, Australia.

BACKGROUND: Australians with cirrhosis have significant practical and psychosocial needs. This longitudinal study examined the association between supportive care needs and health service use and costs, and patient outcomes from June 2017 to December 2018. METHODS: The Supportive Needs Assessment tool for Cirrhosis (SNAC), quality of life (Chronic Liver Disease Questionnaire and Short Form 36), and distress (distress thermometer) were self-reported through an interview at recruitment (n=433). Clinical data were obtained from medical records and through linkage, and health service use and costs through linkage. Patients were grouped as by needs status. Rates of hospital admissions (per person days at risk) and costs were assessed by needs status [incidence rate ratios (IRR), Poisson regression]. Multivariable linear regression was used to assess the differences in SNAC scores by quality of life and distress. Multivariable models included Child-Pugh class, age, sex, recruitment hospital, living arrangements, place of residence, comorbidity burden, and primary liver disease etiology. RESULTS: In adjusted analyses, compared with patients with low/no needs, patients with unmet needs had more cirrhosis-related admissions (adjusted IRR=2.11, 95% CI=1.48-3.13; p<0.001), admissions through the emergency department (IRR=2.99, 95% CI=1.80-4.97, p<0.001), and emergency presentations (IRR=3.57, 95% CI=1.41-9.02; p<0.001). Total hospitalization costs for cirrhosis admissions were higher for those with unmet needs ($431,242 per person days at risk) compared with those with met needs ($87,363 per person days at risk, adjusted cost ratio=3.52, 95%CI=3.49-3.54; p<0.001). In multivariable analysis, increasing overall mean SNAC scores (higher needs) were correlated with poorer quality of life and higher level of distress (p<0.001 for all comparisons). CONCLUSIONS: Patients with cirrhosis and high unmet psychosocial needs and practical and physical needs have poor quality of life, high distress, and very high service use and costs, highlighting the importance of urgently addressing unmet needs.

Childhood cancer survival and avoided deaths in Australia, 1983-2016.

BACKGROUND: Large improvements in childhood cancer survival have been reported over recent decades. Data from cancer registries have the advantage of providing a 'whole of population' approach to gauge the success of cancer control efforts. OBJECTIVES: The aim of this study was to investigate recent survival estimates for children diagnosed with cancer Australia and to examine the extent of changes in survival over the last 35 years. For the first time, we also estimated the number of deaths among Australian children that were potentially avoided due to improvements in survival. METHODS: A retrospective, population-based cohort study design was used. Case information was extracted from the Australian Childhood Cancer Registry for 1983-2016, with follow-up to 31 December 2017. Eligible children were aged 0-14 with a basis of diagnosis other than autopsy or death certificate only. Five-year relative survival was calculated using the semi-complete cohort method for three diagnosis periods (1983-1994, 1995-2006 and 2007-2016), and changes in survival over time were assessed via flexible parametric models. Avoided deaths within 5 years for those diagnosed between 1995 and 2016 were estimated under the assumption that survival rates remained the same as for 1983-1994. RESULTS: Overall 5-year survival within the study cohort (n = 20,871) increased from 72.8% between 1983 and1994 to 86.1% between 2007 and 2016, equating to an adjusted excess mortality hazard ratio of 1.82 (95% confidence interval 1.67, 1.97). Most cancers showed improvements in survival; other gliomas, hepatoblastoma and osteosarcoma were exceptions. Among children diagnosed between 1995 and 2016, 38.7% of expected deaths within 5 years of diagnosis (n = 1537 of 3970) were avoided due to temporal improvements in survival. CONCLUSIONS: Survival for childhood cancer has continued to improve over recent years, thanks mainly to ongoing progress in treatment development combined with improved supportive care. Providing innovative measures of survival, such as avoided deaths, may assist with understanding outcome data produced by cancer registries.

Differences in the pattern and cost of hospital care between Indigenous and non-Indigenous Australians with cirrhosis: an exploratory study.

BACKGROUND: Liver diseases are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. AIMS: This cohort study examined factors associated with hospital admissions and healthcare outcomes among Indigenous Australians with cirrhosis. METHODS: Patient-reported outcomes were obtained by face-to-face interview (Chronic Liver Disease Questionnaire and Short Form 36 (SF-36)). Clinical data were extracted from medical records and through data linkage for 534 patients (25 indigenous). Cumulative overall survival (Kaplan-Meier), rates of hospital admissions and emergency presentations, and costs were assessed by indigenous status. Incidence rate ratios (IRR; Poisson regression) were reported. RESULTS: Indigenous Australians admitted to hospital with cirrhosis had lower educational status compared with non-indigenous patients (79.2% vs 43.4%; P < 0.001). The two groups had, in general, similar clinical characteristics including disease severity (P = 0.78), presence of cirrhosis complications (P = 0.67), comorbidities (P = 0.62), rates of cirrhosis-related admissions (P = 0.86) and 5-year survival (P = 0.30). However, indigenous patients had a lower score in the SF-36 domain related to bodily pain (P = 0.037), more cirrhosis admissions via the emergency department (IRR = 1.42, 95% confidence interval (CI) 1.10-1.83) and fewer planned cirrhosis admissions (IRR = 0.32, 95% CI 0.14-0.72). The total cost for cirrhosis-related hospital admissions for 534 patients over 6 years (July 2012 to June 2018) was A$13.7 million. The cost of cirrhosis-related hospital admissions was double for indigenous patients (cost ratio = 2.04, 95% CI 2.04-2.05). CONCLUSIONS: Our data highlight the disparities in health service use and patient-reported outcomes, despite having similar clinical profiles. Integration between primary care, Aboriginal Community Controlled Health Organisations and liver specialists is critical for appropriate health service delivery and effective use of resources. Chronic liver disease costs the community dearly.

Partnering with support persons and clinicians to improve the health care experiences of patients with cirrhosis.

AIM: To explore the care experiences of Aboriginal and Torres Strait Islander Australians diagnosed with cirrhosis with a focus on support needed. BACKGROUND: Cirrhosis disproportionately affects Indigenous Australians, and liver diseases contribute to the mortality gap between Indigenous and other Australian adults. DESIGN: A qualitative study. METHODS: Using yarning methods, Indigenous patients (n = 13) and support persons (n = 3) were interviewed by an Aboriginal researcher during April-July, 2020. Thematic analysis was used to identify common themes using an inductive approach. RESULTS: Six themes emerged. (1) Experience of diagnosis. This theme included stories of delays in the system, self-awareness of signs and symptoms and relief of being diagnosed. (2) 'Shame, shame, shame'. Experiences of prejudices and discrimination from health professionals, the lack of understanding of cirrhosis among health professionals, and stories about alcohol cessation and counselling around alcohol cessation. (3) Health literacy. Participants' understanding of cirrhosis was variable. While the importance of knowledge was recognised, 'what works for someone might not work for others'. Several patients partnered with their support persons and clinicians to bridge the health literacy gap. (4) Sources of support included family and friends, transport facilities, health professionals and peers. (5) Positive and negative aspects of communication and patient consultation were discussed. (6) Psychosocial counselling to 'look after the caring side'. The need for more mental health care services was raised. CONCLUSION: Barriers related to poor health literacy, stigma and lack of practical and emotional support, and issues with communication and patient consultation, may lead to inequitable access to cirrhosis care and treatment for Indigenous Australians. RELEVANCE TO CLINICAL PRACTICE: Gaining knowledge of the experiences of Indigenous Australians with cirrhosis is important for providing patient-centred and culturally appropriate care. Liver specialist nurses have an important role in bridging the health literacy gap and in supporting Indigenous patients and families.

Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort.

BACKGROUND AND AIMS: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment. METHODS: 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). RESULTS: At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p < 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 > 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. CONCLUSIONS: Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.

Long-term Azithromycin in Children With Bronchiectasis Unrelated to Cystic Fibrosis: Treatment Effects Over Time.

BACKGROUND: Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown. RESEARCH QUESTIONS: (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? STUDY DESIGN AND METHODS: A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect. RESULTS: Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012). INTERPRETATION: Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.

"You feel different in your body": Experiences of fatigue among children undergoing radiotherapy for cancer treatment.

PURPOSE: The aim of this research is to examine the experience and impact of radiotherapy related fatigue in children diagnosed with solid tumours. DESIGN AND METHODS: Children (n = 25) and parents (n = 19) participated in a semi-structured interview on the last week of radiotherapy treatment. The study sample included children who were 6 to 14 years of age, diagnosed with brain or solid tumour, and received radiotherapy as part of their treatment protocol over the period of 6 weeks. Interpretation of data was undertaken through the adoption of thematic analysis approach. RESULTS: Data revealed children's experience and response to fatigue while undergoing radiotherapy. Several recurring themes arose about their experience of fatigue/tiredness while undergoing radiotherapy. Two themes and eight sub themes, namely 'Experience of Fatigue' ("You feel Different in your body", Mood and Feeling, Activity and Occurrence) and 'Response to Fatigue' (Rest and Sleep, Activity, Mood and Concentration and Eating Habit) were identified. CONCLUSIONS: The findings illustrated significant fatigue on activity sleep, rest and mood of children undergoing radiotherapy. PRACTICE IMPLICATIONS: Monitoring and addressing fatigue and its consequences during radiotherapy treatment are essential to improve well-being of children with cancer.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

BACKGROUND: First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection. METHODS: Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU. RESULTS: Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and 'good' adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87-0.99) and treatment initiation in 2018-2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23-21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50-0.99). CONCLUSIONS: Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

Poor disease knowledge is associated with higher healthcare service use and costs among patients with cirrhosis: an exploratory study.

BACKGROUND: Optimal management of cirrhosis is complex, and patients often lack knowledge and skills, which can affect self-management. We assessed patient knowledge about cirrhosis and examined whether knowledge was associated with clinical outcomes, healthcare service use, and healthcare costs. A cross-sectional 'knowledge survey' was conducted during 2018-2020. We assessed patient knowledge about cirrhosis and explore whether knowledge was associated with clinical outcomes, healthcare service use, and costs. METHODS: Patients with cirrhosis (n = 123) completed a 'knowledge survey'. We calculated the proportion of correct answers to eight questions deemed to be "key knowledge" about cirrhosis by an expert panel, and dichotomized patients as 'good knowledge'/'poor knowledge'. Clinical data, healthcare costs, and health-related quality of life (SF-36) were available. RESULTS: 58.5% of patients had 'good knowledge' about cirrhosis. Higher education level was associated with higher odds of having 'good knowledge' about cirrhosis (adjusted-OR = 5.55, 95%CI 2.40-12.84). Compared to patients with 'poor knowledge', those with 'good knowledge' had a higher health status in the SF-36 physical functioning domain (p = 0.011), fewer cirrhosis-related admissions (adjusted incidence rate ratio [IRR] = 0.59, 95%CI 0.35-0.99) and emergency presentations (adj-IRR = 0.34, 95%CI 0.16-0.72), and more planned 1-day cirrhosis admissions (adj-IRR = 3.96, 95%CI 1.46-10.74). The total cost of cirrhosis admissions was lower for patients with 'good knowledge' (adj-IRR = 0.30, 95%CI 0.29-0.30). CONCLUSION: Poor disease knowledge is associated with increased use and total cost of healthcare services. Targeted educational interventions to improve patient knowledge may be an effective strategy to promote a more cost-effective use of healthcare services.

Targeted antiviral treatment of hepatitis B virus in culturally and linguistically diverse populations to achieve elimination targets in Australia.

The majority of Australia's hepatitis B virus (HBV) burden is borne by culturally and linguistically diverse (CALD) populations, and antiviral treatment is the mainstay of intervention. Using modelling, we estimated the impact of targeted antiviral treatment scale-up and changes in migration on HBV-related mortality and HBV elimination in CALD populations in Australia. We fitted a deterministic mathematical model based on the natural history of HBV and the Australian migration effect in four CALD population groups according to country of birth. We used three antiviral treatment scale-up scenarios: baseline (9.3% coverage); intermediate (coverage of 80% of patients eligible for antiviral therapy by 2030); and optimistic (coverage of 20% of all patients living with HBV by 2022). Our model predicted that if the baseline treatment is followed between 2015 and 2030, the number of chronic HBV cases and HBV-related mortality will increase. Following the optimistic scale-up, the number of new HBV cases could be reduced by 78%, 73%, 74% and 83% in people born in Asia-Pacific, Europe, Africa and the Middle East, and Americas, respectively, between 2015 and 2030. An optimistic treatment scale-up could result in a 19.2%-24.5% reduction in HBV-related mortality and a 15%-25% reduction in HCC-related mortality in CALD populations between 2015 and 2030. In conclusion, our findings highlight that targeted antiviral treatment for CALD populations provides significant health system benefits by reducing HBV-related complications from cirrhosis and HCC. Expanded antiviral treatment programmes focusing on high-prevalence CALD populations may be an effective strategy to reduce HBV-related morbidity and mortality.

The Impact of Social Workers in Cirrhosis Care: a Systematic Review.

Purpose of review: To report social workers' involvement in supporting patients with cirrhosis. Recent findings: Six intervention studies (three published in the past 3 years) highlighed the potential role of social worker-led interventions to improve the outcomes of patients with cirrhosis. In studies of patients with alcohol-related liver disease (n = 4), social workers conducted psychosocial assessments, screened for substance use disorder and psychological distress, coordinated referrals to addiction services, and provided relapse prevention therapy. In studies including transplant recipients or candidates (n = 2), social workers focused on psychosocial interventions. In two studies (n = 1 patient with alcohol-related liver disease; n = 1 transplant recipients), social workers provided practical support (e.g., housing, transportation). Most articles provided limited information about the intervention and the role of the social worker, making comparisons of the studies difficult. Summary: More high-quality evidence is needed to formally assess the impact of social workers in improving the outcomes of patients with cirrhosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s11938-022-00381-2.