National Health Medical Research Council Research Articles

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

Transfer or tailor? Implementing a technology‐supported intervention for noncommunicable diseases across contexts

Transfer or tailor? Implementing a technology‐supported intervention for noncommunicable diseases across contexts

End-of-trial inflammatory biomarkers, lipid levels, creatine kinase and markers of renal and liver function in the LoDoCo2 trial

Abstract Background The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduced major cardiovascular events in patients with chronic coronary artery disease (CAD). The effect of long-term colchicine treatment on inflammatory biomarkers and markers reflecting renal and liver function have not been investigated yet. Purpose This substudy examines levels of inflammatory biomarkers, lipid fractions, creatine kinase (CK) and markers of renal and liver function at close-out of the trial. Methods The LoDoCo2 trial randomly assigned patients with chronic CAD to colchicine 0.5 mg once daily or placebo. Blood samples were drawn during close-out visits after a median follow-up of 32.7 (interquartile range [IQR] 24.0–48.6) months. Results Assignment to colchicine was associated with lower levels of high-sensitivity C-Reactive Protein (0.94 mg/L [0.53–1.93] vs. 1.24 mg/L [0.73–2.55]; −24.2%; p<0.01) and interleukin-6 (2.70 ng/L [1.79–4.18] vs. 3.16 ng/L [2.07–4.95]; −14.9%; p<0.01), but was not associated with any differences in lipid fractions or markers of renal function. Although CK levels were higher after colchicine (123.0 U/L, [84.0–184.0] vs. 110.0 U/L, [77.0–164.0], p<0.01), the number of participants with marked elevations of CK (>5 times upper limit of normal [ULN]) was low and not different between treatment groups. Levels of alanine aminotransferase (ULN 40 U/L) and albumin (ULN 50 U/L) were higher (p<0.01) in the colchicine group compared to placebo (30.0 U/L [22.0–40.0] vs. 26.0 U/L [19.0–34.0] and 43.01 g/L±2.39 vs. 42.64 g/L±2.48, respectively). There were no differences in gamma-glutamyl transferase or bilirubin. Conclusion Long-term low-dose colchicine in patients with chronic CAD was associated with lower levels of hs-CRP and IL-6 but was not associated with clinically important differences in lipid fractions, CK, renal or liver function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The National Health Medical Research Council of AustraliaThe Netherlands Organization for Health Research and Development

The effects of colchicine in patients with diabetes mellitus and chronic coronary artery disease: a post-hoc analysis of the LoDoCo2-trial

Abstract Background Atherosclerosis is an inflammatory disease and is accelerated by diabetes mellitus (DM). Patients with chronic coronary artery disease (CAD) who also have DM are at high risk of recurrent cardiovascular events. The role of inflammation in atherosclerosis is well established, whereas the role of inflammation on incident and progression of DM has been hypothesized. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in particular, may play an important role in the onset and progression of T2DM. The anti-inflammatory drug colchicine attenuates the NLRP3-inflammasome. The Low-Dose Colchicine 2 (LoDoCo2) trial showed that colchicine reduces cardiovascular risk in patients with chronic CAD. Purpose The purpose of this study was to assess the effects of colchicine in patients with chronic CAD and DM on cardiovascular events as well as the effect of colchicine on the development of new-onset DM. Methods The LoDoCo2 trial randomized 5522 to placebo or colchicine, with a median follow-up of 28.6 months (interquartile range 20.5–44.4). The primary endpoint was a composite of cardiovascular death, spontaneous myocardial infarction, ischaemic stroke, or ischaemia-driven revascularization. Secondary outcomes consisted of the aforementioned events, separately. Cox proportional hazards models were used to investigate univariable associations between DM status for all endpoints in the placebo group. The interactions between treatment group and DM status were evaluated with the addition of treatment and the treatment-by-DM variable interaction. Results In total, 1007 participants (18.2%) had DM at baseline. The hazard ratio for the primary endpoint was 0.87 (95% CI, 0.61–1.25) in those with DM and 0.64 (95% CI, 0.51–0.80) in those without DM (p for interaction>0.05). Treatment effects of colchicine were consistent over all secondary endpoints (p for interaction>0.05). The incidence of new-onset DM was 1.5% (34/2270) in the colchicine group and 2.2% (49/2245) in the placebo group (p=0.10). Participants with DM were at higher risk for all endpoints. The primary composite end point in the placebo group occurred in 13.0% (67/515) patients with DM and in 8.8% (197/2245) of the patients without DM (unadjusted hazard ratio 1.54 [95% CI 1.16–2.03, p<0.01]) compared to the group without DM. DM was also strongly associated with the occurrence of all secondary end points. Conclusion This study shows that the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The data indicate that larger trials are needed to assess whether colchicine reduces the incidence of new-onset DM. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): National Health Medical Research Council of Australia and the Netherlands Organization for Health Research and Development

PROTOCOL: Barriers and facilitators to stakeholder engagement in health guideline development: A qualitative evidence synthesis.

There is a need for the development of comprehensive, global, evidence-based guidance for stakeholder engagement in guideline development. Stakeholders are any individual or group who is responsible for or affected by health- and healthcare-related decisions. This includes patients, the public, providers of health care and policymakers for example. As part of the guidance development process, Multi-Stakeholder Engagement (MuSE) Consortium set out to conduct four concurrent systematic reviews to summarise the evidence on: (1) existing guidance for stakeholder engagement in guideline development, (2) barriers and facilitators to stakeholder engagement in guideline development, (3) managing conflicts of interest in stakeholder engagement in guideline development and (4) measuring the impact of stakeholder engagement in guideline development. This protocol addresses the second systematic review in the series. The objective of this review is to identify and synthesise the existing evidence on barriers and facilitators to stakeholder engagement in health guideline development. We will address this objective through two research questions: (1) What are the barriers to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? (2) What are the facilitators to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? A comprehensive search strategy will be developed and peer-reviewed in consultation with a medical librarian. We will search the following databases: MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, PsycInfo, Scopus, and Sociological Abstracts. To identify grey literature, we will search the websites of agencies who actively engage stakeholder groups such as the AHRQ, Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR), INVOLVE, the National Institute for Health and Care Excellence (NICE) and the PCORI. We will also search the websites of guideline-producing agencies, such as the American Academy of Pediatrics, Australia's National Health Medical Research Council (NHMRC) and the WHO. We will invite members of the team to suggest grey literature sources and we plan to broaden the search by soliciting suggestions via social media, such as Twitter. We will include empirical qualitative and mixed-method primary research studies which qualitatively report on the barriers or facilitators to stakeholder engagement in health guideline development. The population of interest is stakeholders in health guideline development. Building on previous work, we have identified 13 types of stakeholders whose input can enhance the relevance and uptake of guidelines: Patients, caregivers and patient advocates; Public; Providers of health care; Payers of health services; Payers of research; Policy makers; Program managers; Product makers; Purchasers; Principal investigators and their research teams; and Peer-review editors/publishers. Eligible studies must describe stakeholder engagement at any of the following steps of the GIN-McMaster Checklist for Guideline Development. All identified citations from electronic databases will be imported into Covidence software for screening and selection. Documents identified through our grey literature search will be managed and screened using an Excel spreadsheet. A two-part study selection process will be used for all identified citations: (1) a title and abstract review and (2) full-text review. At each stage, teams of two review authors will independently assess all potential studies in duplicate using a priori inclusion and exclusion criteria. Data will be extracted by two review authors independently and in duplicate according to a standardised data extraction form. The results of this review will be used to inform the development of guidance for multi-stakeholder engagement in guideline development and implementation. This guidance will be official GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group guidance. The GRADE system is internationally recognised as a standard for guideline development. The findings of this review will assist organisations who develop healthcare, public health and health policy guidelines, such as the World Health Organization, to involve multiple stakeholders in the guideline development process to ensure the development of relevant, high quality and transparent guidelines.

Guidelines development protocol and findings: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease

BackgroundDiabetes-related foot disease (DFD) is a leading cause of the Australian disease burden. The 2011 Australian DFD guidelines were outdated. We aimed to develop methodology for systematically adapting suitable international guidelines to the Australian context to become the new Australian evidence-based guidelines for DFD.MethodsWe followed the Australian National Health Medical Research Council (NHMRC) guidelines for adapting guidelines. We systematically searched for all international DFD guideline records. All identified records were independently screened and assessed for eligibility. Those deemed eligible were further assessed and included if scoring at least moderate quality, suitability and currency using AGREE II and NHMRC instruments. The included international guidelines had all recommendations extracted into six sub-fields: prevention, wound classification, peripheral artery disease, infection, offloading and wound healing. Six national panels, each comprising 6–8 multidisciplinary national experts, screened all recommendations within their sub-field for acceptability and applicability in Australia using an ADAPTE form. Where panels were unsure of any acceptability and applicability items, full assessments were undertaken using a GRADE Evidence to Decision tool. Recommendations were adopted, adapted, or excluded, based on the agreement between the panel’s and international guideline’s judgements. Each panel drafted a guideline that included all their recommendations, rationale, justifications, and implementation considerations. All underwent public consultation, final revision, and approval by national peak bodies.ResultsWe screened 182 identified records, assessed 24 full text records, and after further quality, suitability, and currency assessment, one record was deemed a suitable international guideline, the International Working Group Diabetic Foot Guidelines (IWGDF guidelines). The six panels collectively assessed 100 IWGDF recommendations, with 71 being adopted, 27 adapted, and two excluded for the Australian context. We received 47 public consultation responses with > 80% (strongly) agreeing that the guidelines should be approved, and ten national peak bodies endorsed the final six guidelines. The six guidelines and this protocol can be found at: https://www.diabetesfeetaustralia.org/new-guidelines/ConclusionNew Australian evidence-based guidelines for DFD have been developed for the first time in a decade by adapting suitable international guidelines. The methodology developed for adaptation may be useful for other foot-related conditions. These new guidelines will now serve as the national multidisciplinary best practice standards of DFD care in Australia.

Colchicine in Patients with Chronic Coronary Disease

BackgroundEvidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.MethodsIn a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.ResultsA total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P=0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).ConclusionsIn a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.)

Randomised controlled trials evaluating endometrial scratching: assessment of methodological issues.

Do randomised controlled trials (RCTs) evaluating endometrial scratching suffer from methodological issues including insufficient trial registration, statistical errors or irreproducibility, randomisation errors or miscellaneous issues? The majority of RCTs investigating endometrial scratching have methodological issues. A large number of small RCTs investigating the effectiveness of endometrial scratching prior to in vitro fertilisation (IVF) and intrauterine insemination (IUI)/intercourse have reported favourable findings. Subsequently, systematic reviews incorporating these RCTs yielded meta-analyses in favour of endometrial scratching. Endometrial scratching has been widely adopted by infertility specialists around the world. Recently, an international RCT including 1364 women reported no benefit from endometrial scratching before IVF. We evaluated several methodological issues of RCTs investigating the effectiveness of endometrial scratching prior to IVF and IUI/intercourse. We identified 25 RCTs for IVF and 12 RCTs for IUI/intercourse with full-text publication. We assessed the RCTs on the following criteria: adequacy of trial registration, statistical issues (description of statistical methods and reproducibility of univariable statistical analysis), excessive similarity or difference in baseline characteristics that is not compatible with chance (Monte Carlo simulations and Kolmogorov-Smirnov test) and miscellaneous methodological issues. Of 25 RCTs evaluating endometrial scratching prior to IVF, only eight (32%) had adequate trial registration. In total, 10 (40%) RCTs had issues regarding statistical methods. Nine (69%, 13 applicable) RCTs had at least one inconsistency between reported and reproduced univariable statistical analysis for categorical baseline/intermediate characteristics. Statistical results of at least one outcome were not reproducible in 14 (74%, 19 applicable) RCTs. Only two (8%) RCTs had none of the above issues. Suggested by the simulations, these RCTs did not significantly violate the null hypothesis that the baseline characteristics were the results of a properly conducted randomisation process (P= 0.4395).Of 12 IUI/intercourse RCTs, only 2 (17%) had adequate trial registration. In total, five (42%) studies had issues of statistical methods. Inconsistency between reported and reproduced univariable analysis for baseline/intermediate categorical variable(s) was found in four (57%, 7 applicable) RCTs. Statistical analysis was not reproducible for at least one outcome in eight (80%, 10 applicable) studies. All RCTs had at least one of the above issues. These RCTs were inconsistent with the null hypothesis that their baseline characteristics were the results of proper randomised allocation (P= 1.659*10-7). We were unable to assess RCTs which were not published as full-text papers. We could not analyse individual participant data to investigate possible reasons for statistical inconsistencies. The method to infer the likelihood of proper random sampling rests on assumptions including independent baseline characteristics, simple randomisation and no publication bias. The methodological issues common to RCTs evaluating endometrial scratching may have biased the results of the trials. Further development and validation of these novel methods may be helpful for the critical appraisal of RCTs. No external funding was sought to support this work. B.W.M. is supported by a National Health Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. D.W. is supported by a grant from the Paracelsus Medical University Salzburg, Austria (PMU Research Fund-PMU FFF Number: L-18/02/006-WET) and by Drs Haackert Foundation, Germany. S.L. is an author of a trial included in this study, an author of an included systematic review and a Cochrane editor. All other authors have no conflicts of interest. N/A.

1746P - Comparing cancer patients’ and support persons’ preferences for the type of consultation and the format of information provided when making a treatment decision

Background: Cancer patients and their support persons often feel overwhelmed when being confronted with their diagnosis and treatment options. Such information is commonly provided during one consultation with their clinician. We compared cancer patients’ and their support persons’ preferences for: i) attending one 40-minute consultation or two 20-minute consultations when making a treatment decision; and ii) receiving additional information in written form only or in both written and online forms. Methods: An Australian cross-sectional survey, using a discrete choice experiment (DCE), of 159 adult medical oncology patients, and 64 of their support persons. Participants were presented with four hypothetical scenarios and asked to indicate their most and least preferred option. They were told that both treatments would have the same impact on participants’ life expectancy, and that there would be no difference between the scenarios in terms of when treatment would start. Results: 147 patients and 59 support persons completed the DCE. The proportions of patients and support persons choosing each scenario did not differ statistically significantly from each other (p > 0.05). Of the four scenarios, most patients and support persons preferred to receive two consultations along with written and online information (n = 65, 44% and n = 30, 51% respectively). Significantly more participants preferred to receive two shorter consultations rather than one longer consultation when this was combined with written and online information (p < 0.05). Conclusions: When making a cancer treatment decision, both patients and support persons seem to prefer to receive two shorter consultations combined with written and online information. Clinicians should consider offering this consultation style. Legal entity responsible for the study: Anne Herrmann. Funding: This study was funded by a Strategic Research Partnership Grant [CSR 11-02] from the Cancer Council New South Wales to the Newcastle Cancer Control Collaborative (New-3C), and by a Partnership Project [APP1059760] from the National Health & Medical Research Council (NHMRC). The authors also received funding support from the Hunter Cancer Research Alliance Implementation Science Flagship Program, the Hunter New England Local Health District, and the Australian Research Council. Infrastructure funding was provided by the University of Newcastle and Hunter Medical Research Institute. Disclosure: All authors have declared no conflicts of interest.

Platelet Activating Factor Receptor (PAFR) Regulates Colitis‐induced Pulmonary Inflammation

Inflammatory bowel disease (IBD) is a progressive disease that includes Crohn's diseases and ulcerative colitis. Over one third of IBD patients have secondary organ pathologies and pulmonary manifestations are common. The platelet activating factor receptor (PAFR) plays a critical role in regulating inflammation and it is expressed on epithelial cells and neutrophils in both colon and lung. Having identified increased expression of PAFR in both the gastrointestinal (GI) tract and lungs of mice with dextran sulfate sodium (DSS) colitis, we hypothesised that PAFR was a mediator of the pulmonary inflammation associated with colitis. We aimed to elucidate the role of PAFR in gut‐lung inflammatory cross‐talk using of the DSS‐induced experimental model of colitis (7 days). DSS mice were treated with PAFR antagonist CV6209 both intranasally and intravenously and lung, colon and blood were assessed for inflammatory cells and mediators by qPCR, immunoblot, immunohistochemistry and flow cytometry. We demonstrated that DSS‐induced colitis resulted in inflammation in mouse bronchoalveolar lavage fluid (BALF) and lungs, as well as increased PAFR protein levels in lungs and colons. Pulmonary neutrophils in DSS animals showed increased PAFR staining. Bacterial 16S mRNA expression were also increased in mouse lungs after 7 days DSS challenge. Both intravenous and intranasal inhibition of PAFR by CV6209 reduced colitis‐induced numbers of neutrophils, but not macrophages, in mouse lungs. Inhibition of PAFR also reduced levels of TNF and IL‐1b proteins and bacterial 16S expression in mouse lungs. Importantly, intravenous administration of CV6209 reduced colitis pathology, TNF and IL‐1b protein levels in mouse colons after 7 days DSS challenge. In the DSS model, increased PAFR protein expression was associated with inflammasome activation, characterized by increased NLRP3 and mature caspase‐1 proteins, however inhibition of PAFR by CV6209 reduced NLRP3 and caspase‐1 levels after DSS challenge in mouse lungs. In vitro, NLRP3, activated caspase‐1 and secreted IL‐1b protein levels were increased in human alveolar epithelial cell culture (A549) after 24h LPS stimulation, and this was inhibited by treatment with CV6209. These data suggest that PAFR regulates colitis‐induced lung inflammation by IL‐1b protein activation via the NLRP3 inflammasome signalling pathway. PAFR may act as an inflammasome‐activating pattern recognition receptor during mucosal inflammation thus is a potential therapeutic target for lung inflammation associated with colitis and bacteraemia.Support or Funding InformationThis study was supported by a grant from National Health Medical Research Council (NHMRC) AustraliaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Coercion and HIV self-testing in Chinese men who have sex with men: implementation data from a cross-sectional survey

BackgroundThe wide range of interventions to promote HIV testing might inadvertently contribute to coerced testing. There has been concern about coerced HIV self-testing in non-research settings where there is minimal supervision. The aim of this study was to examine the prevalence and correlates of coerced HIV testing among men who have sex with men (MSM) in China. MethodsIn July 2016, we recruited MSM from eight cities through BlueD, a gay social network mobile application. Data on sociodemographics, HIV self-testing, HIV facility testing, test coercion, condomless sex in the past 3 months, and transactional sex were collected. Coerced testing was defined as someone (partner, friend, employer, or others) forcing the participant to take an HIV test. Multivariable logistic regression was used to examine correlates of coerced testing among MSM who had ever received HIV testing. Findings1312 men were included, most of whom were young (mean age 26·9 years [SD 6·3]). 1002 (76%) men were identified as gay, and 685 (52%) men had used HIV self-testing. 64 (15%) men reported coerced testing, and 39 of these men were forced to have a self-test. Adjusting for age, education, income, and residence, men who reported coerced testing were more likely to have ever self-tested for HIV (adjusted odds ratio 4·25; 95% CI 2·23–8·09). Coerced testing was more common among men who had sex with casual partners in exchange for gifts or money (3·34; 1·90–5·86) than among men who did not report transactional sex. Coerced testing was also more common among MSM who reported condomless anal sex in the preceding 3 months (2·38; 1·43–3·98) than among men who did not report condomless anal sex. InterpretationHIV test coercion is uncommon among MSM in China, but is more likely in men who used HIV self-tests. As HIV self-testing is scaled up worldwide, research and enhanced post-test surveillance are needed. FundingNational Institute of Allergy and Infectious Diseases (1R01AI114310-01) and the Australian National Health Medical Research Council (APP1104781). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, or in the writing of the Abstract.

Adherence to a Mediterranean Diet (MedDiet) for 6 months improves dietary quality and dietary inflammatory index in a western population: results from the Mediterranean diet for cognition and cardiovascular health in the elderly (MedLey) study

Inflammation is thought to be an underlying pathophysiological cause of a range of chronic diseases including cardiovascular disease (CVD). Diet is a modifiable risk factor for CVD and can influence the inflammatory process depending on the quality of the diet. Western diets, typically characterised by processed foods, red and processed meats, refined carbohydrates and added sugars, have been shown to be positively associated with inflammatory markers, while a Mediterranean diet, rich in plant foods and low in processed foods, has been shown to have a contrasting effect. The dietary inflammatory index (DII) was developed to determine the inflammatory potential of a dietary pattern. Positive DII scores indicate a pro‐inflammatory diet and negative scores indicate an anti‐inflammatory diet. This opportunistic study sought to evaluate the change in dietary quality and dietary inflammatory index following the administration of a traditional MedDiet in older Australian adults.152 Australian men and women (mean age 71±5yrs) were recruited for the MedLey study. Participants were randomly allocated either a MedDiet (n=80) or continue their habitual diet (HabDiet) (n=72) for 6 months. Volunteers followed a prescribed MedDiet plan under dietetic supervision. All volunteers attended the clinic on a fortnightly basis to have their weight measured, discuss the intervention and receive study foods. Dietary intake was calculated using 3‐day weighed food records. Data was analysed using linear regression.137 volunteers completed the trial (MedDiet n=70, HabDiet n=67). Our volunteers were able to comply with the MedDiet throughout the intervention (92% compliance rate) according to daily monitoring of food intake. At baseline, 14% of the population were meeting recommended intakes for vegetables and 54.9% for fruits, and 5.1% for dairy foods.. With administration of a traditional MedDiet, the MedDiet group increased their mean daily intake of vegetables (+60g), fruit (+123g), dairy (+98g), fish (+42g), nuts (+33g), legumes (29g,) and decreased their intake of meat (−21g) and discretionary foods (−168g). The HabDiet achieved only minor changes at 4 months, although decreased their intake of discretionary foods 95g but in contrast also decreased their mean daily intake of dairy foods (−19g) and fish (−12g). The baseline DII was −0.10±1.71 (mean±SD) for our Australian population (n=152). For the MedDiet group the DII score was −1.40±0.20 and −1.47±0.20 at 2 and 4 months of the intervention, respectively, whilst the HabDiet DII score did not change significantly (0.47±0.21 at 2 months and 0.54±0.21 at 4 months).This dietary pattern was sustainable to follow for 6 months as evident by the high compliance rate and facilitated improves in the quality of the diet by increases plant based foods and decreases in discretionary food. This resulted in changes in the DII promoting a low inflammatory diet which could be beneficial for healthy ageing and the avoidance of chronic disease.Support or Funding InformationThis project was supported by a grant from the National Health Medical Research Council of Australia.

The effect of endotracheal tubes versus laryngeal mask airways on perioperative respiratory adverse events in infants: a randomised controlled trial

Perioperative respiratory adverse events (PRAE) are the most common critical incidents in paediatric anaesthesia and occur more often in infants. Use of laryngeal mask airways (LMAs) is associated with reduced PRAE compared with endotracheal tubes in older children (>1 year). We aimed to evaluate the effect of these devices on the incidence of PRAE in infants. We did a randomised controlled trial at the Princess Margaret Hospital for Children in Perth (WA, Australia) by recruiting infants (aged 0-12 months) undergoing general (with or without regional or local) anaesthesia with anticipated fentanyl dose 1 μg/kg or lower for minor elective surgery. We excluded patients contraindicated for LMA or endotracheal tube; who had known cardiac disease or airway or thoracic malformations; who were receiving midazolam premedication; who were undergoing airway, thoracic, or abdomen surgery at the time of participation; and if the parents did not speak English. Written parental or guardian consent was obtained before enrolment. Participants were randomly assigned (1:1), by computer-generated variable block randomisation, to receive an LMA (PRO-Breathe, Well Lead Medical Co Ltd, Panyu, China) or an endotracheal tube (Microcuff, Halyard Health Inc, Atlanta, GA, USA). Sealed randomisation envelopes were used to conceal device assignment. An interim analysis was planned once half the number of infants needed (145) had been recruited. The primary outcome was incidence of PRAE, assessed in the intention-to-treat population. The institutional ethics committee at the Princess Margaret Hospital for Children granted ethical approval (1786/EP). The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000250033). The trial began on July 8, 2010, and was ended early on May 7, 2015, after the interim analysis results met the study stopping rules. During this time, 239 infants were assessed and 181 eligible infants were randomly assigned to receive an LMA (n=85) or an endotracheal tube (n=95). Four infants were not included in the analysis (two due to cancelled procedures, one did not meet inclusion criteria, and one with missing dataset). In the intention-to-treat analysis, PRAE occurred in 50 (53%) infants in the endotracheal tube group and in 15 (18%) infants in the LMA group (risk ratio [RR] 2·94, 95% CI 1·79-4·83, p<0·0001). Laryngospasm and bronchospasm (major PRAE) were recorded in 18 (19%) infants in the endotracheal tube group and in three (4%) infants in the LMA group (RR 5·30, 95% CI 1·62-17·35, p=0·002). No deaths were reported. In infants undergoing minor elective procedures, LMAs were associated with clinically significantly fewer PRAE and lower occurrence of major PRAE (laryngospasm and bronchospasm) than endotracheal tubes. This difference should be a consideration in airway device selection. Princess Margaret Hospital Foundation, National Health and Australian Medical Research Council, Stan Perron Charitable Trust, and Callahan Estate.

Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies.

What is the degree of intrinsic insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) and the relative contribution of BMI to overall IR based on meta-analysis of gold standard insulin clamp studies? We report an inherent reduction (-27%) of insulin sensitivity (IS) in PCOS patients, which was independent of BMI. PCOS is prevalent, complex and underpinned by IR but controversies surround the degree of intrinsic IR in PCOS, the effect of BMI and the impact of the different diagnostic criteria (NIH versus Rotterdam) in PCOS. A systematic review and meta-analysis of Medline and All EBM databases was undertaken of studies published up to 30 May2015. Studies were included if premenopausal women diagnosed with PCOS were compared with a control group for IS, measured by the gold standard euglycaemic-hyperinsulinaemic clamp. The systematic review adheres to the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analyses were performed using mixed modelling and magnitude-based inferences expressed as mean effect ±99% CI. We inferred the effect was small, moderate or large relative to a smallest important change of -3.7% or 3.8% derived by standardisation. Effects were deemed unclear when the CI overlapped smallest important positive and negative values. Effects were qualified with probabilities reflecting uncertainty in the magnitude of the true value (likely, 75-95%; very likely, 95-99.5%; most likely, >99.5%). A total of 4881 articles were returned from the search. Of these, 28 articles were included in the meta-analysis. Overall IS was lower in women with PCOS compared with controls (mean effect -27%, 99% CI ±6%; large, most likely lower). A higher BMI exacerbated the reduction in IS by -15% (±8%; moderate, most likely lower) in PCOS compared with control women. There was no clear difference in IS between women diagnosed by the original National Institutes of Health (NIH) criteria alone compared with those diagnosed by the Rotterdam criteria. Low levels of sex hormone-binding globulin (SHBG) were associated with reduced levels of IS (-10%, ±10%; small, very likely negative), which was not confounded by BMI. This systematic review and meta-analysis inherited the confounding problems of small sample sizes, missing data (e.g. some hormones, waist and hip girths) and the lack of Rotterdam criteria phenotype reporting, limiting the evidence synthesis and meta-analysis. BMI has a greater impact on IS in PCOS than in controls. SHBG appears a potentially valuable marker of IR in PCOS, whereas testosterone after adjustment for BMI demonstrated an unexpected interplay with IS which warrants further investigation. This work was supported by grants from the National Health & Medical Research Council (NHMRC), grant number 606553 (H.J.T., N.K.S.), as well as Monash University. H.J.T. is an NHMRC Research Fellow. N.K.S. is supported through the Australian Government's Collaborative Research Networks (CRN) programme. The funding bodies played no role in the design, methods, data management or analysis or in the decision to publish. All authors declare no conflict of interests. N/A.

ASCIA‐P18: ASCIA PRACTICAL INFORMATION ON HOW TO INTRODUCE SOLID FOODS TO INFANTS

Parents require access to practical, evidence based advice about infant feeding that is consistent with current recommendations. This is particularly important when infants are considered to be at risk of developing food allergy or have a known food allergy, as parents may be reluctant to introduce allergenic solid foods to these infants. Updated ASCIA guidelines for infant feeding and allergy prevention were released in May 2016 after the Centre for Food & Allergy Research (CFAR) Infant Feeding Summit. These guidelines include three key recommendations agreed on at the Summit. The ASCIA Paediatric and Dietitian committees recognised the need for additional practical advice about infant feeding for parents to be used in conjunction with the guidelines. ASCIA practical infant feeding information ASCIA Practical information on how to introduce solid foods to infants and ASCIA Guidelines for Infant Feeding and Allergy Prevention provide comprehensive feeding advice that is consistent with National Health & Medical Research Council (NHMRC) and WHO.

The implication of amino acid mutations at flavivirus NS1-2A cleavage site on NS1’ protein production

This work was supported by a grant from National Health & Medical Research Council (NHMRC) of Australia.

Review article: systematic review of three key strategies designed to improve patient flow through the emergency department.

To explore the literature regarding three key strategies designed to promote patient throughput in the ED. CINAHL, Medline, PubMed, Scopus and Australian Government databases were searched for articles published between 1980 and 2014 using the key search terms ED flow/throughput, ED congestion, crowding, overcrowding, models of care, physician-assisted triage, medical assessment units, nurse practitioner, did not wait (DNW) and ED length of stay (LOS). Abstracts and articles not published in English and articles published before 1980 were excluded from the review. Quantitative and qualitative studies were considered for inclusion. The National Health Medical Research Council (NHMRC) Level of Evidence Hierarchy (2009) was applied to included studies. Twenty-one articles met criteria for review. The level of evidence assessed using the NHMRC guidelines of studies ranged from I to IV, with the majority falling into the Level II-2 (n = 6) and III-3 (n = 9) range. ED LOS was the outcome most often reported. Study quality was limited with few studies adjusting for confounding factors. Only one level I systematic review was included in this review. Advanced practice nursing roles, physician-assisted triage and medical assessment units are models of care that can positively impact ED throughput. They have been shown to decrease ED LOS and DNW rates. Confounding factors, such as site specific staffing requirements, patient acuity and rest-of-hospital processes, can also impact on patient throughput through the ED.

Looking back at the John Mitchell Crouch Fellowship: the most prestigious research award of the Royal Australasian College of Surgeons.

The John Mitchell Crouch Fellowship is a generous endowment made to the Royal Australasian College of Surgeons (RACS) by the young neurosurgeon's family, following his death from a brain tumour. In this article, we examine the significance and legacy of the grant since its inception in 1979. This is the highest level of research fellowship awarded by the RACS recognizing early career excellence, as part of its significant research funding programme (over $1.7 million in 2015). John Mitchell Crouch recipients have been pioneers in various areas of medicine where they have developed new technologies, established research centres, improved patient safety and military surgery and embraced evidence-based medicine. The funds they received have directly contributed to research published in numerous highly respected peer-reviewed journals such as The New England Journal of Medicine; established new laboratories, helped fund clinical trials and allowed new directions of research to be pursued. Recipients of the John Mitchell Crouch Fellowship have been recognized with many awards including 11 Australian and New Zealand Honours to date. Many other significant research funds have been subsequently bestowed, including over 120 National Health Medical Research Council (NHMRC) grants to Australian and New Zealand recipients subsequent to their Fellowship. This article also shows the range of disciplines in which the award has supported cutting-edge research leading to benefits for patients and health care.

Are Australian podiatrists meeting best practice in the management of diabetic foot complications?

Background Diabetic foot complications are the leading cause of lower extremity amputation and diabetes-related hospitalisation in Australia. Studies demonstrate significant reductions in amputations and hospitalisation when health professionals implement best practice management. Whilst other nations have surveyed health professionals on specific diabetic foot management, to the best of the authors' knowledge this appears not to have occurred in Australia. The primary aim of this study was to examine Australian podiatrists' diabetic foot management compared with best practice recommendations by the Australian National Health Medical Research Council.