National Health And Medical Research Council Research Articles

The carbon footprint of hospital diagnostic imaging in Australia

SummaryBackgroundPathology testing and diagnostic imaging together contribute 9% of healthcare's carbon footprint. Whilst the carbon footprint of pathology testing has been undertaken, to date, the carbon footprint of the four most common imaging modalities is unclear.MethodsWe performed a prospective life cycle assessment at two Australian university-affiliated health services of five imaging modalities: chest X-ray (CXR), mobile chest X-ray (MCXR), computerised tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US). We included scanner electricity use and all consumables and associated waste, including bedding, imaging contrast, and gloves. Analysis was performed using both attributional and consequential life cycle assessment methods. The primary outcome was the greenhouse gas footprint, measured in carbon dioxide equivalent (CO2e) emissions.FindingsMean CO2e emissions were 17·5 kg/scan for MRI; 9·2 kg/scan for CT; 0·8 kg/scan for CXR; 0·5 kg/scan for MCXR; and 0·5 kg/scan for US. Emissions from scanners from standby energy were substantial. When expressed as emissions per additional scan (results of consequential analysis) impacts were lower: 1·1 kg/scan for MRI; 1·1 kg/scan for CT; 0·6 kg/scan for CXR; 0·1 kg/scan for MCXR; and 0·1 kg/scan for US, due to emissions from standby power being excluded.InterpretationClinicians and administrators can reduce carbon emissions from diagnostic imaging, firstly by reducing the ordering of unnecessary imaging, or by ordering low-impact imaging (X-ray and US) in place of high-impact MRI and CT when clinically appropriate to do so. Secondly, whenever possible, scanners should be turned off to reduce emissions from standby power. Thirdly, ensuring high utilisation rates for scanners both reduces the time they spend in standby, and apportions the impacts of the reduced standby power of a greater number of scans. This therefore reduces the impact on any individual scan, maximising resource efficiency.FundingHealthy Urban Environments (HUE) Collaboratory of the Maridulu Budyari Gumal Sydney Partnership for Health, Education, Research and Enterprise MBG SPHERE. The National Health and Medical Research Council (NHMRC) PhD scholarship

TGF-β and CIS inhibition synergistically enhance natural killer cell-based immunity

Abstract Immune “checkpoint” inhibitor antibodies have revolutionized cancer therapy and function by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8 T cells. Recent studies have also shown similar programs in other effector lymphocyte populations such as natural killer (NK) cells. NK cells are key to cancer immunosurveillance, particularly in settings of metastasis. They are dependent on the cytokine IL-15 for their survival, development, and function, with ablation of the IL-15 signaling inhibitor CIS (Cish), shown to enhance NK cell anti-tumor immunity by increasing NK cell fitness in the tumor microenvironment (TME). The TME has also been shown to impair NK cell fitness via the production of immunosuppressive transforming growth factor (TGF)-β, even in the presence of high IL-15 signaling. Here, taking advantage of sophisticated proteomics and transcriptomics methods with computational biology analysis we identified an unexpected interaction between CIS and the TGF-β signaling pathway in NK cells. Independently, for the first time a Cish- and Tgfbr2-double-deficient NK cells were generated by our group, which displayed both hyper-responsiveness to IL-15 and hypo-responsiveness to TGF-β, with dramatically enhanced immunity against multiple mouse models of cancer. Remarkable, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development and this resistance is dependent on NK cell hyper-activity. This study contributes to the understanding on how targeting multiple suppressive pathways unveils a new immunotherapy approach that might have broad therapeutic interventions, particularly by enhancing NK cell effector functions during disease. This work is supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (#1140406), the US Department of Defense – Breast Cancer Research Program – Breakthrough Award Level 1 (#BC200025), the ANZSA SRG Grant, and was supported by a grant (#1158085) awarded through the Priority-driven Collaborative Cancer Research Scheme and co-funded by Cancer Australia and Cure Cancer.

High-intensity training elicits greater improvements in cardio-metabolic and reproductive outcomes than moderate-intensity training in women with polycystic ovary syndrome: a randomized clinical trial.

Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)? HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT. Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT. This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019. Women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% peak heart rate, N = 14) or HIIT (>90% peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic-hyperinsulinaemic clamp). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition. Both HIIT and MICT improved VO2peak (HIIT; Δ 5.8 ± 2.6 ml/kg/min, P < 0.001 and MICT; Δ 3.2 ± 2 ml/kg/min, P < 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (β = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (β = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (β = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04). This study has a small sample size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication. Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS. This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose. ACTRN12615000242527. 19 February 2015. 27 May 2016.

Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) as a Screening Marker for Familial Adenomatous Polyposis (FAP): Systematic Literature Review and Screening Recommendations.

PurposeFamilial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a highly specific phenotypical marker for FAP that can be used in screening at-risk individuals. Screening recommendations including morphological subclassification were formulated with supporting literature.MethodsA systematic literature review with a comprehensive search strategy was conducted using online databases. Manual searches of bibliographies and reference lists were also performed. Studies meeting inclusion criteria were graded with respect to their hierarchy of evidence and strength of recommendations according to the National Health and Medical Research Council (NHMRC) guidelines of Australia.ResultsAlmost 4500 participants were analysed across 28 included studies. The mean specificity of CHRPE as a phenotypical screening marker of FAP was 89% (standard deviation (SD); 14) with a mean sensitivity of 79% (SD; 8). The mean prevalence of CHRPE amongst FAP participants; at-risk participants were found to be 76% (SD; 24) and 37% (SD; 21) respectively. Bilateralism and multiple lesion number ≥3 are features highly specific for FAP.ConclusionCHRPE was found to be a non-invasive, rapid, early phenotypical screening marker of FAP. Clinical recognition further allows increased gene analysis efficiency. The absence of CHRPE alone cannot exclude FAP. Our screening recommendations provide guidance to clinicians on evidence based CHRPE assessment. We would advocate inclusion of ocular examinations as part of a three-pronged approach, along with endoscopy and genetic testing, for efficient, timely FAP assessment in at-risk individuals.

Population-wide contribution of medically assisted reproductive technologies to overall births in Australia: temporal trends and parental characteristics.

Population-wide contribution of medically assisted reproductive technologies to overall births in Australia: temporal trends and parental characteristics.

De novo and recurrent metastatic breast cancer - A systematic review of population-level changes in survival since 1995.

SummaryBackgroundAdvances in breast cancer (BC) care have reduced mortality, but their impact on survival once diagnosed with metastasis is less well described. This systematic review aimed to describe population-level survival since 1995 for de novo metastatic BC (dnMBC) and recurrent MBC (rMBC).MethodsWe searched MEDLINE 01/01/1995–12/04/2021 to identify population-based cohort studies of MBC reporting overall (OS) or BC-specific survival (BCSS) over time. We appraised risk-of-bias and summarised survival descriptively for MBC diagnoses in 5-year periods from 1995 until 2014; and for age, hormone receptor and HER2 subgroups.FindingsWe identified 20 eligible studies (14 dnMBC, 1 rMBC, 5 combined). Potential sources of bias in these studies were confounding and shorter follow-up for the latest diagnosis period.For dnMBC, 13 of 14 studies reported improved OS or BCSS since 1995. In 2005–2009, the median OS was 26 months (range 24–30), a median gain of 6 months since 1995–1999 (range 0–9, 4 studies). Median 5-year OS was 23% in 2005–2009, a median gain of 7% since 1995–1999 (range -2 to 14%, 4 studies). For women ≥70 years, the median and 5-year OS was unchanged (1 study) with no to modest difference in relative survival (range: -1·9% (p = 0.71) to +2·1% (p = 0.045), 3 studies). For rMBC, one study reported no change in survival between 1998 and 2006 and 2007–2013 (median OS 23 months). For combined MBC, 76–89% had rMBC. Three of four studies observed no change in median OS after 2000. Of these, one study reported median OS improved for women ≤60 years (1995–1999 19·1; 2000–2004 22·3 months) but not >60 years (12·7, 11·6 months).InterpretationPopulation-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification.FundingSL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21–001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).

Glaucoma Suspects: The Impact of Risk Factor-Driven Review Periods on Clinical Load, Diagnoses, and Healthcare Costs.

PurposeTo model the healthcare impact (clinical attendance time and financial cost) and clinical outcomes (glaucoma diagnoses) of different risk factor–driven review frequencies for glaucoma suspect patients up until the point of discharge or diagnosis.MethodsMedical records of 494 glaucoma suspects were examined to extract the clinical diagnosis. Two criteria for review periods were defined, based on contrasting stringency from established clinical guidelines: American Academy of Ophthalmology (AAO), more stringent/less frequent; and the Australian National Health and Medical Research Council (NHMRC), less stringent/more frequent. We used these data to model patient outcomes and healthcare costs using a Markov model.ResultsThe less stringent/more frequent criterion resulted in more high-risk glaucoma suspects requiring more frequent review compared with the more stringent/less frequent criterion. Across the 15 Markov cycles (7.5 years), the less stringent/more frequent review criterion resulted in 6.6% more diagnoses and fewer overall clinical visits (14.7%) and reduced cost per diagnosis by 12% to 32% (P < 0.0001). The number of glaucoma diagnoses made using each criterion converged at 2.5 to 3 years.ConclusionsThe stringency of risk assessments for glaucoma suspects impacts review periods and therefore clinical load, healthcare costs, and diagnosis rates. Using current testing methods, more frequent review periods appear advantageous for diagnostic efficiency, with both lower clinic load and lower cost up until the point of discharge or glaucoma diagnosis.Translational RelevanceA less stringent criterion for assessing the risk of developing glaucoma potentially offers a more cost-effective method for reviewing glaucoma suspects, especially within the first 2.5 years.

Interventions to reduce suicidal thoughts and behaviours among people in contact with the criminal justice system: A global systematic review.

SummaryBackgroundPeople who experience incarceration die by suicide at a higher rate than those who have no prior criminal justice system contact, but little is known about the effectiveness of interventions in other criminal justice settings. We aimed to synthesise evidence regarding the effectiveness of interventions to reduce suicide and suicide-related behaviours among people in contact with the criminal justice system.MethodsWe searched Embase, PsycINFO, MEDLINE, and grey literature databases for articles published between 1 January 2000 and 1 June 2021. The protocol was registered with PROSPERO (CRD42020185989).FindingsThirty-eight studies (36 primary research articles, two grey literature reports) met our inclusion criteria, 23 of which were conducted in adult custodial settings in high-income, Western countries. Four studies were randomised controlled trials. Two-thirds of studies (n=26, 68%) were assessed as medium quality, 11 (29%) were assessed as high quality, and one (3%) was assessed as low quality. Most had considerable methodological limitations and very few interventions had been rigorously evaluated; as such, drawing robust conclusions about the efficacy of interventions was difficult.InterpretationMore high-quality evidence from criminal justice settings other than adult prisons, particularly from low- and middle-income countries, should be considered a priority for future research.FundingThis work was funded by the Australian government's National Suicide Prevention Taskforce. RB is supported by a National Health and Medical Research Council (NHMRC) Emerging Leader Investigator Grant (EL2; GNT2008073). MW is supported by a NHMRC Postgraduate Scholarship (GNT1151103). SF was funded by the NIHR HTA Programme (HTA Project:16/159/09).

Evidence and consensus-based clinical practice guidelines for management of overweight and obesity in midlife women: An AIIMS-DST initiative.

Evidence and consensus-based clinical practice guidelines for management of overweight and obesity in midlife women: An AIIMS-DST initiative.

Australian guideline on management of diabetes-related foot infection: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease.

BackgroundDiabetes-related foot infections cause substantial morbidity and mortality, both globally and in Australia. There is a need for up-to-date evidence-based guidelines to ensure optimal management of patients with diabetes-related foot infections. We aimed to identify and adapt high quality international guidelines to the Australian context to become the new Australian evidence-based guideline for people with a diabetes-related foot infection.MethodsFollowing Australian National Health and Medical Research Council (NHMRC) procedures we identified the 2019 International Working Group on the Diabetic Foot (IWGDF) guidelines as suitable for adaptation to the Australian context. Guidelines were screened, assessed and judged by an expert panel for the Australian context using the guideline adaptation frameworks ADAPTE and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Judgements led to recommendations being adopted, adapted or excluded, with additional consideration regarding their implementation, monitoring and future research for the Australian context. Clinical pathways were then developed to assist implementation.ResultsOf 36 original diabetes-related foot infection IWGDF sub-recommendations, 31 were adopted, four were adapted and one was excluded. Adaption was primarily undertaken due to differences or clarification of the sub-recommendations’ intended population. One sub-recommendation was excluded due to substantial differences in judgements between the panel and IWGDF and unacceptable heterogeneity of the target population. Therefore, we developed 35 evidence-based sub-recommendations for the Australian context that should guide best practice diagnosis and management of people with diabetes-related foot infection in Australia. Additionally, we incorporated these sub-recommendations into two clinical pathways to assist Australian health professionals to implement these evidence-based sub-recommendations into clinical practice. The six guidelines and the full protocol can be found at: https://www.diabetesfeetaustralia.org/new-guidelines/.ConclusionsA new national guideline for the diagnosis and management of people with diabetes-related foot infections were successfully developed for the Australian context. In combination with simplified clinical pathway tools they provide an evidence-based framework to ensure best management of individuals with diabetes-related foot infections across Australia and highlight considerations for implementation and monitoring.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13047-022-00545-4.

Australian guideline on wound healing interventions to enhance healing of foot ulcers: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease

BackgroundDiabetes-related foot ulceration (DFU) has a substantial burden on both individuals and healthcare systems both globally and in Australia. There is a pressing need for updated guidelines on wound healing interventions to improve outcomes for people living with DFU. A national expert panel was convened to develop new Australian evidence-based guidelines on wound healing interventions for people with DFU by adapting suitable international guidelines to the Australian context.MethodsThe panel followed National Health and Medical Research Council (NHMRC) procedures to adapt suitable international guidelines by the International Working Group of the Diabetic Foot (IWGDF) to the Australian context. The panel systematically screened, assessed and judged all IWGDF wound healing recommendations using ADAPTE and GRADE frameworks for adapting guidelines to decide which recommendations should be adopted, adapted or excluded in the Australian context. Each recommendation had their wording, quality of evidence, and strength of recommendation re-evaluated, plus rationale, justifications and implementation considerations provided for the Australian context. This guideline underwent public consultation, further revision and approval by ten national peak bodies.ResultsThirteen IWGDF wound healing recommendations were evaluated in this process. After screening, nine recommendations were adopted and four were adapted after full assessment. Two recommendations had their strength of recommendations downgraded, one intervention was not currently approved for use in Australia, one intervention specified the need to obtain informed consent to be acceptable in Australia, and another was reworded to clarify best standard of care. Overall, five wound healing interventions have been recommended as having the evidence-based potential to improve wound healing in specific types of DFU when used in conjunction with other best standards of DFU care, including sucrose-octasulfate impregnated dressing, systemic hyperbaric oxygen therapy, negative pressure wound therapy, placental-derived products, and the autologous combined leucocyte, platelet and fibrin dressing. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new-guidelines/ConclusionsThe IWGDF guideline for wound healing interventions has been adapted to suit the Australian context, and in particular for geographically remote and Aboriginal and Torres Strait Islander people. This new national wound healing guideline, endorsed by ten national peak bodies, also highlights important considerations for implementation, monitoring, and future research priorities in Australia.

Genetic overlap analysis of endometriosis and asthma identifies shared loci implicating sex hormones and thyroid signalling pathways.

Is there a shared genetic or causal association of endometriosis with asthma or what biological mechanisms may underlie their potential relationships? Our results confirm a significant but non-causal association of endometriosis with asthma implicating shared genetic susceptibility and biological pathways in the mechanisms of the disorders, and potentially, their co-occurrence. Some observational studies have reported a pattern of co-occurring relationship between endometriosis and asthma; however, there is conflicting evidence and the aetiology, as well as the underlying mechanisms of the relationship, remain unclear. We applied multiple statistical genetic approaches in the analysis of well-powered, genome-wide association study (GWAS) summary data to comprehensively assess the relationship of endometriosis with asthma. Endometriosis GWAS from the International Endogene Consortium (IEC, 17 054 cases and 191 858 controls) and asthma GWAS from the United Kingdom Biobank (UKB, 26 332 cases and 375 505 controls) were analysed. Additional asthma data from the Trans-National Asthma Genetic Consortium (TAGC, 19 954 cases and 107 715 controls) were utilized for replication testing. We assessed single-nucleotide polymorphism (SNP)-level genetic overlap and correlation between endometriosis and asthma using SNP effect concordance analysis (SECA) and linkage disequilibrium score regression analysis (LDSC) methods, respectively. GWAS meta-analysis, colocalization (GWAS-PW), gene-based and pathway-based functional enrichment analysis methods were applied, respectively, to identify SNP loci, genomic regions, genes and biological pathways shared by endometriosis and asthma. Potential causal associations between endometriosis and asthma were assessed using Mendelian randomization (MR) methods. SECA revealed significant concordance of SNP risk effects across the IEC endometriosis and the UKB asthma GWAS. Also, LDSC analysis found a positive and significant genetic correlation (rG = 0.16, P = 2.01 × 10-6) between the two traits. GWAS meta-analysis of the IEC endometriosis and UKB asthma GWAS identified 14 genome-wide significant (Pmeta-analysis < 5.0 × 10-8) independent loci, five of which are putatively novel. Three of these loci were consistently replicated using TAGC asthma GWAS and reinforced in colocalization and gene-based analyses. Additional shared genomic regions were identified in the colocalization analysis. MR found no evidence of a significant causal association between endometriosis and asthma. However, combining gene-based association results across the GWAS for endometriosis and asthma, we identified 17 shared genes with a genome-wide significant Fisher's combined P-value (FCPgene) <2.73 × 10-6. Additional analyses (independent gene-based analysis) replicated evidence of gene-level genetic overlap between endometriosis and asthma. Biological mechanisms including 'thyroid hormone signalling', 'abnormality of immune system physiology', 'androgen biosynthetic process' and 'brain-derived neurotrophic factor signalling pathway', among others, were significantly enriched for endometriosis and asthma in a pathway-based analysis. The GWAS for endometriosis data were sourced from the International Endogen Consortium (IEC) and can be accessed by contacting the consortium. The GWAS data for asthma are freely available online at Lee Lab (https://www.leelabsg.org/resources) and from the Trans-National Asthma Genetic Consortium (TAGC). Given we analysed GWAS datasets from mainly European populations, our results may not be generalizable to other ancestries. This study provides novel insights into mechanisms underpinning endometriosis and asthma, and potentially their observed relationship. Findings support a co-occurring relationship of endometriosis with asthma largely due to shared genetic components. Agents targeting 'selective androgen receptor modulators' may be therapeutically relevant in both disorders. Moreover, SNPs, loci, genes and biological pathways identified in our study provide potential targets for further investigation in endometriosis and asthma. National Health and Medical Research Council (NHMRC) of Australia (241,944, 339,462, 389,927, 389,875, 389,891, 389,892, 389,938, 443,036, 442,915, 442,981, 496,610, 496,739, 552,485, 552,498, 1,026,033 and 1,050,208), Wellcome Trust (awards 076113 and 085475) and the Lundbeck Foundation (R102-A9118 and R155-2014-1724). All researchers had full independence from the funders. Authors do not have any conflict of interest.

The CKD bowel health study: understanding the bowel health and gastrointestinal symptom management in patients with chronic kidney disease: a mixed-methods observational longitudinal study (protocol)

BackgroundGastro-intestinal (GI) intolerance is a frequently reported outcome in patients with kidney failure receiving maintenance dialysis and those who have received kidney transplants. Symptoms of GI intolerance (diarrhoea, constipation, bloating, abdominal pain, heart burn, and reflux) are associated with significant reduction in quality of life, morbidity, and increased used of healthcare resources. Having chronic kidney disease (CKD), together with related changes in diet and medication, may alter the gut microbiota and the microbial-derived uraemic metabolites that accumulate in kidney failure, and contribute to various complications including chronic diarrhoea, opportunistic infections, and drug-related colitis. Despite the high disease burden among patients with kidney replacement therapies, GI symptoms are often under-recognised and, consequently limited resources and strategies are devoted to the management of gastrointestinal complications in patients with CKD.MethodsThe CKD Bowel Health Study is a multi-centre mixed-methods observational longitudinal study to better understand the bowel health and GI symptom management in patients with CKD. The program comprises of a longitudinal study that will assess the burden and risk factors of GI intolerance in patients treated with maintenance dialysis; a semi-structured interview study that will describe experiences of GI intolerance (including symptoms, treatment, self-management) in transplant candidates and recipients; and a discrete choice experience to elicit patient preferences regarding their experiences and perspectives of various intervention strategies for the management of GI symptoms after kidney transplantation.DiscussionThis proposed program of work aims to define the burden the GI intolerance in patients with kidney failure and generate evidence on the patients’ experiences of GI intolerance and their perspectives on their clinical and own management strategies of these symptoms, ensuring a patient-centred approach to guide clinical decision making and to inform the best study design for intervention trials.Trial registrationThis study is registered on the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000548831. This study has been approved by the Western Sydney Local Health District Human Research Ethics Committee of New South Wales Health (HREC ETH03007). This study is supported by a National Health and Medical Research Council (NHMRC) Australia Investigator Grant (APP1195414), and an NHMRC Australia Postgraduate Scholarship (APP2005244).

Feasibility of national living guideline methods: The Australian Stroke Guidelines

ObjectiveMaintaining clinical guideline currency has been one challenge to traditional guideline development. This paper describes the methods used to maintain a large national guideline for stroke management. Study design and settingThe Australian Stroke Clinical Guidelines are developed to meet Australian National Health and Medical Research Council (NHMRC) standards. Monthly surveillance is conducted for new systematic reviews and randomised controlled studies. Included studies undergo data extraction followed by preparation of updated evidence-to-decision frameworks which are used to inform updates, or development of new recommendations. Small writing groups made up of clinical experts and those with lived experience review and agree on changes, which are finally reviewed by a multidisciplinary Guidelines Steering Group. Draft changes are developed and published using the online MAGICapp platform, with dissemination and promotion via traditional methods as well as social media. ResultsEach month approximately 350 abstracts are considered, covering 96 clinical topics and taking on average 16 h to review. There have been four major guideline updates covering 34 new and updated recommendations. ConclusionIt is feasible to use ‘living’ methods to maintain the Australian Clinical Guidelines for Stroke Management. Further work is now needed to understand the impact of living guidelines.

Is the contribution of Australian research to the national 2019 clinical practice guidelines for keratinocyte cancer adequate? A simple analysis

Introduction: The Australian 2002 National Health and Medical Research Council (NHMRC) treatment guidelines for non-melanoma skin cancer (NMSC) were updated in 2008. At this time, the lack of high-quality Australian research conducted between 2002 to 2008 was noted. The primary aim of the present study was to assess the improvement in the quantity and quality of Australian research in the 2019 keratinocyte cancer guidelines. Secondary aims included an assessment of the quantity and quality of Australian research in comparison to the guidelines provided by the other selected countries, and an evaluation of the improvements in the Australian contribution since 2008. Method: Surgical (Sx) and radiotherapy (RT) treatment sections were interrogated. The analysis was simple. Each reference was counted as one unit. The quantity assessment was carried out by categorizing the references according to their country of origin: Australia, United Kingdom (UK), United States (US) and European Union (EU) countries, which were grouped as one country (EU) for the purpose of this study. The number of references from each country were then added up. To assess for quality, all references were ranked according to the American Society of Plastic Surgeons (ASPS) rating scale. A quality ratio for each country was then calculated by dividing the total number of prospective trials (i.e., levels I and II) by the number of retrospective studies (level III and lower) from each country if the numbers were sufficient. To evaluate the Australian improvement since 2008, Australian references were first categorized according to their year of publication (2002 to 2017), and then allocated to one of four bins of class intervals representing time periods. Results: Twenty-five of the 133 Sx references in the 2019 guidelines were Australian, which was less than the US (58) and EU (37), but better than the UK (12). Quality ratios were: Australia 0.8, UK 1.4, US 0.31, and EU 0.48. Of the 238 RT references, Australia contributed 53, US 107, EU 62, and UK 16. Quality ratios were: Australia 0.06, UK 0.3, US 0.18, and EU 0.34. Australia’s contribution to the UK and US RT guidelines were evaluated. For the UK RT guidelines (11 references), Australia contributed 3, UK 1, US 2 and EU 5. For the US ASTRO guidelines (101 references), Australia contributed 20, UK 1, US 44 and EU 36. Quality ratios were Australia 0.11, US 0.19 and EU 0.2. For Australian research overtime (2002-2017), the quantity and quality of Sx papers are decreasing; whereas for RT, the quantity is increasing but the quality remains poor. Conclusion: The contribution of Australian research to Australia’s own keratinocyte cancer guidelines is not the highest and did not improve over the period of evaluation. The same can be stated for Australia’s research contribution to the UK and US RT guidelines. Australia needs to do more high-quality research.

A rapid global review of strategies to improve influenza vaccination uptake in Australia

ABSTRACT This study aimed to identify effective strategies for improving the uptake of influenza vaccination and to inform recommendations for influenza vaccination programs in Australia. A rapid systematic review was conducted to assimilate and synthesize peer-reviewed articles identified in PubMed. The National Health and Medical Research Council (NHMRC) Hierarchy of Evidence was used to appraise the quality of evidence. A systematic search identified 4373 articles and 52 that met the inclusion criteria were included. The evidence suggests influenza vaccination uptake may be improved by interventions that (1) increase community/patient demand and access to influenza vaccine and overcome practice-related barriers; (2) reinforce the critical role healthcare providers play in driving influenza vaccination uptake. Strategies such as standing orders, reminder and recall efforts were successful in improving influenza vaccination rates. Community pharmacies, particularly in regional/remote areas, are well positioned to improve influenza vaccine coverage. The findings of this rapid review can be utilized to improve the performance of influenza immunization programs in Australia and other countries with comparable programs; and recommend priorities for future evaluation of interventions to improve influenza vaccination uptake.

Lifetime Cost of HIV Management in Australia: An Economic Model

Background: Antiretroviral therapy (ART) for HIV has significantly reduced morbidity and mortality, but the drugs can be expensive. This study aims to estimate the lifetime cost of HIV management from the Australian healthcare perspective. Methods: A Markov cohort model, consisting of 21 health states based on CD4 count and line of ART, simulated disease progression over the lifetime of persons living with HIV. We reported costs using 2019 Australian dollars (A$) at a discount rate of 3·5% per annum. One-way sensitivity analysis was used to assess the impact of model inputs, and probabilistic sensitivity analyses were conducted to calculate the 95% confidence intervals for the lifetime cost estimate. Findings: The average discounted lifetime cost of HIV management was A$282,093 [95% CI: $194,206 – 421,345]. The largest proportion of lifetime cost was due to ART (92%). The lifetime cost was most sensitive to third- and second-line ART costs, followed by the probability of failing third-line therapy for those with CD4 count <200. A 20% or 50% reduction in patented ART costs would reduce the lifetime cost to $243,638 and $161,400, respectively. Replacing patented ART drugs with currently available generic equivalents reduced the lifetime cost to A$141,345. Interpretation: The relatively high lifetime costs for managing HIV means ongoing investment will be required to provide care and treatment to people living with HIV, and supports the urgent need to avert new infections. Reducing the price of ARTs (including consideration of generic drugs) would have the most significant impact on lifetime costs. Funding: JJO is supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leader Investigator Grant (GNT1193955). The funding body did not influence the research or decision to publish. The Kirby Institute is funded by the Australian Government Department of Health, and is affiliated with the Faculty of Medicine, UNSW Sydney, Australia. Declaration of Interest: The authors declare that they do not have any competing interest.

Communicating with patients and the public about COVID-19 vaccine safety: recommendations from the Collaboration on Social Science and Immunisation.

Communicating with patients and the public about COVID-19 vaccine safety: recommendations from the Collaboration on Social Science and Immunisation.

Trends in management of hip and knee osteoarthritis in general practice in Australia over an 11-year window: a nationwide cross-sectional survey

BackgroundWe aimed to describe trends in knee and hip OA management by general medical practitioners (GPs) in Australia. MethodsWe analysed cross-sectional survey data from the Bettering the Evaluation and Care of Health (BEACH) program (1,000 randomly-selected GPs annually recording 100 consecutive patient encounters) over two periods: Period one April 1, 2005-March 31, 2010 and period two April 1, 2010-March 31, 2016. This included data from 10,738 GPs and 1,073,800 patient encounters with 6,565 GPs and 9,196 patient encounters for hip/knee OA. Data were summarized using descriptive statistics and 95% confidence intervals around point estimates. FindingsRate of knee OA problems managed by GPs increased in period two (7•1 (6•9-7•4) vs 6•2 (95% CI 6•0-6•5) per 1,000 all encounters), with a similar trend for hip OA. Encounter rates rose for some subgroups but remained stable for vulnerable subgroups. Although use of Medicare chronic disease management items, referral to allied health professionals and advice/education and lifestyle management (knee OA) increased, rates remained low. Use of MRI imaging rose. Overall medication rates were stable but substantially higher than non-pharmacological treatments. Declining reliance on non-steroidal anti-inflammatory drugs and glucosamine and increased reliance on paracetamol (knee OA) and opioids were demonstrated. InterpretationGPs in Australia are more frequently managing knee and hip OA. While small changes in GP management actions occured, rates of recommended first-line non-pharmacological treatments remained low and imaging, medications, and surgical referral rates high. Strategies are needed to optimise lifestyle management and reduce low-value care, with attention to healthcare disparities. FundingFunding was provided for this report by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Translational Research in Musculoskeletal Pain (#1079078).

Rethinking the use of ‘vulnerable’

Rethinking the use of ‘vulnerable’