National Health And 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†.

Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials

Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS. We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640. From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n=961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens+lifestyle were superior to metformin+lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]:-1.59 [-3.06,-0.12], p=0.03; I2=74%), SHBG (7.70nmol/l [0.75, 14.66], p=0.03; I2=0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97,-0.26], p=0.03; I2=0% and-1.12 [-1.44,-0.79], p<0.0001, I2=0%, respectively), but were not superior to placebo+lifestyle for hirsutism (-0.93, [-3.37, 1.51], p=0.45; I2=76%) or SHBG (9.72nmol/l [-0.71, 20.14], p=0.07; I2=31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58,-2.39], p<0.0001, I2=1%), and resulted in lower androstenedione levels (-0.30ng/ml [-0.50,-0.10], p=0.004; I2=0%). Combination treatment with anti-androgens+metformin+lifestyle resulted in lower testosterone compared with metformin+lifestyle (-0.29nmol/l [-0.52,-0.06], p=0.01; I2=61%), but there were no differences in hirsutism when anti-androgens+metformin+lifestyle were compared with either anti-androgens+lifestyle or metformin+lifestyle. In limited meta-analyses (n=2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP±placebo, with no differences in other outcomes. Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics. National Health and Medical Research Council (NHMRC) of Australia Monash University.

Development of CRISPR/Cas13a-based assays for the diagnosis of Schistosomiasis.

Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this disease. CRISPR-based technology has rapidly accelerated the development of a revolutionary and powerful diagnostics platform, resulting in the advancement of a class of ultrasensitive, specific, cost-effective and portable diagnostics, typified by applications in COVID-19/cancer diagnosis. We developed CRISPR-based diagnostic platform SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of Schistosoma japonicum and S.mansoni by combining recombinase polymerase amplification (RPA) with CRISPR-Cas13a detection, measured via fluorescent or colorimetric readouts. We evaluated SHERLOCK assays by using 150 faecal/serum samples collected from Schistosoma-infected ARC Swiss mice (female), and 189 human faecal/serum samples obtained from a S.japonicum-endemic area in the Philippines and a S.mansoni-endemic area in Uganda. The S.japonicum SHERLOCK assay achieved 93-100% concordance with gold-standard qPCR detection across all the samples. The S.mansoni SHERLOCK assay demonstrated higher sensitivity than qPCR and was able to detect infection in mouse serum as early as 3 weeks post-infection. In human samples, S.mansoni SHERLOCK had 100% sensitivity when compared to qPCR of faecal and serum samples. These schistosomiasis diagnostic assays demonstrate the potential of SHERLOCK/CRISPR-based diagnostics to provide highly accurate and field-friendly point-of-care tests that could provide the next generation of diagnostic and surveillance tools for parasitic neglected tropical diseases. Australian Infectious Diseases Research Centre seed grant (2022) and National Health and Medical Research Council (NHMRC) of Australia (APP1194462, APP2008433).

O-229 Long term features of PCOS and Medical treatment

Abstract Objective: To develop and translate comprehensive evidence-based guidelines for diagnosis, assessment and treatment, to improve the lives of those with polycystic ovary syndrome (PCOS) worldwide. Participants: Health professional and consumer/ patients informed priorities. International society-nominated panels included consumers, and experts in reproductive endocrinology, obstetrics, gynaecology, paediatrics, endocrinology, primary care, psychology, dietetics, exercise physiology, sleep, bariatric/ metabolic surgery, public health, other co-opted experts, evidence synthesis and translation. Evidence: Best practice guideline development involved extensive evidence synthesis and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework covered evidence quality, feasibility, acceptability, cost, implementation and recommendation strength. Process: Governance included international advisory and project, guideline development, consumer and translation committees. The Centre for Research Excellence in Women’s Health in Reproductive Life, funded by the Australian National Health and Medical Research Council (NHMRC), and led by Monash University, partnered with the American Society for Reproductive Medicine, Endocrine Society, European Endocrine Society and European Society of Human Reproduction and Embryology. Another 30 collaborating organisations engaged. Overall 52 systematic and three narrative reviews, informed international guideline groups, generating evidence-based and consensus recommendations and practice points for 55 clinical questions. Collaborating/ partnering organisations and NHMRC methodological experts led peer review. Recommendations: After diagnosing PCOS, assessment and management should include reproductive, metabolic, cardiovascular, dermatologic, sleep and psychological features. A reproductive health plan is recommended including diagnosis and support in adolescence, lifelong healthy lifestyle / prevention of weight gain, fertility optimisation, preconception risk mitigation and recognition of PCOS as a high-risk pregnancy condition requiring identification, screening, monitoring and management. Metabolic risk factors, diabetes, cardiovascular disease and sleep disorders are increased in PCOS, with screening and management recommended. Increased premenopausal endometrial cancer risk should be recognised. Depressive and anxiety symptoms are significantly increased, with universal screening recommended. Greater awareness of psychological features including eating disorders, body image and quality of life impacts is recommended. Life-style intervention is the first line treatment for PCOS, but in many cases medication is also needed. Combined oral contraceptive pills are first line pharmacological treatment for menstrual irregularity and hyperandrogenism, with no specific recommended preparation, and a preference for lower dose and less side-effects. Metformin is recommended primarily for metabolic features noting greater efficacy than inositol, which offers more limited clinical benefits. Metformin is not routinely recommended for use in pregnancy. Laser therapy is effective and recommended for hair reduction in identified subgroups, whilst anti-androgens have more limited recommendations. Anti-obesity agents and bariatric/ metabolic surgery may be considered based on general population guidelines, balancing benefits and side effects. Overall, evidence was low to moderate quality. Based on high prevalence and significant health impact, greater priority, education, funding and research is strongly recommended.

Community awareness and use of anti-Müllerian hormone testing in Australia: a population survey of women.

What is the anti-Mullerian hormone (AMH) test usage, awareness, and perceived reasons for testing in a representative community sample of women in Australia? : Among women aged 18-55 years, 13% had heard about AMH testing and 7% had had an AMH test, with the top three reasons for testing including due to infertility investigations (51%), considering pregnancy and wanting to understand their chances (19%) or to find out if a medical condition had affected fertility (11%). The growing availability of direct-to-consumer AMH testing has raised concerns about overuse, however as most AMH tests are paid for privately by consumers, data on test usage is not publicly available. National cross-sectional survey of 1773 women, conducted in January 2022. Females aged 18-55 years were recruited from the representative 'Life in Australia' probability-based population panel and completed the survey online or by telephone. Main outcome measures included if and how participants had heard about AMH testing, whether they had ever had an AMH test, main reason for testing and test access. Of the 2423 women who were invited 1773 responded (73% response rate). Of these, 229 (13%) had heard about AMH testing and 124 (7%) had had an AMH test. Testing rates were highest among those currently aged 35-39 years (14%) and associated with educational attainment. Almost all accessed the test through their general practitioner or fertility specialist. Reasons for testing were: part of an infertility investigation (51%), considering pregnancy and wanting to understand chances of conceiving (19%), finding out if a medical condition had affected fertility (11%), curiosity (9%), considering egg freezing (5%), and considering delaying pregnancy (2%). Although the sample was large and mostly representative, it was over-represented by people holding a university degree and under-represented by people aged 18-24, however, we used weighted data where possible to account for this. All data were self-reported so there is a risk of recall bias. The number of survey items was also restricted, so the type of counselling women received prior to testing, reasons for declining an AMH test or test timing were not measured. Whilst most women reported having an AMH test for appropriate reasons, about one third had it for reasons not supported by evidence. Public and clinician education about the lack of utility of AMH testing for women not undergoing infertility treatment is needed. This project was supported by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence grant (1104136) and Program grant (1113532). T.C. is supported by an NHMRC Emerging Leader Research Fellowship (2009419). B.W.M. reports research funding, consultancy and travel support from Merck. D.L. is the Medical Director of City Fertility NSW and reports consultancy for Organon, Ferring, Besins and Merck. The authors have no other competing interests. N/A.

The Australian evidence-based clinical practice guideline for attention deficit hyperactivity disorder.

The objective of this article was to provide an overview of the development and recommendations from the Australian evidence-based clinical practice guideline for attention deficit hyperactivity disorder (ADHD). The guideline aims to promote accurate and timely identification and diagnosis, and optimal and consistent treatment of ADHD. Development integrated the best available evidence with multidisciplinary clinical expertise and the preferences of those with lived experience, underpinned by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. The 23 guideline development group members included psychiatrists, paediatricians, general practitioners, psychologists, speech pathologists, occupational therapists, educators, Indigenous psychologists, and people with a lived experience; with two independent chairs and a methodologist. Where appropriate, evidence reviews from the National Institute for Health and Care Excellence (NICE) 2018 'Attention Deficit Hyperactivity Disorder: Diagnosis and Management' guideline were updated. Fifty prioritised clinical questions were addressed in 14 systematic reviews (new and updated from NICE 2018) and 28 narrative reviews. The 113 clinical recommendations apply to young children (5 years and under), children, adolescents and adults. They provide guidance for clinicians on identification, screening, diagnosis, multimodal treatment and support, including pharmacological and non-pharmacological interventions. The guideline and supporting information are available online: https://adhdguideline.aadpa.com.au/. The guideline was approved by the National Health and Medical Research Council (NHMRC) of Australia and relevant medical and allied health professional associations. It is anticipated that successful implementation and uptake of the guideline by organisations, health care providers and other professionals will increase delivery of evidence-based treatment and improve health outcomes for the more than 800,000 Australians with ADHD.

A mechanism for the elimination of IgE plasma cells

Abstract The proper regulation of IgE production safeguards against allergic disease, highlighting the importance of mechanisms that restrict IgE plasma cell (PC) survival. IgE PCs have unusually high surface B cell receptor (BCR) expression, yet the functional consequences of ligating this receptor are unknown. Here, we found that BCR ligation induced BCR signaling in IgE PCs followed by their elimination. In cell culture, exposure of IgE PCs to cognate antigen or anti-BCR antibodies induced apoptosis. IgE PC depletion correlated with the affinity, avidity, amount, and duration of antigen exposure and required the BCR signalosome components Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, BCR ligation by injection of cognate antigen or anti-IgE depleted IgE PCs. These findings establish a mechanism for the elimination of IgE PCs through BCR ligation. This has important implications for allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments. This research was supported by the National Institute of Allergy and Infections Diseases of the National Institutes of Health under Award Number R01AI130470; the Program for Breakthrough Biomedical Research, which is partially funded by the Sandler Foundation; the Sandler Asthma Basic Research Center; and the Cardiovascular Research Institute at the University of California, San Francisco. C.D.C.A. was a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. A.K.W-V was supported by a Doctoral Foreign Study Award from the Canadian Institute of Health Research, funding reference number DFD-170769. D.M.T. and M.J.R. were funded by National Health and Medical Research Council (NHMRC) Australia by an Investigator Award (APP1175411) and Ideas Grant (APP1185294), respectively. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Artificial intelligence (AI) for breast cancer screening: BreastScreen population-based cohort study of cancer detection.

Artificial intelligence (AI) has been proposed to reduce false-positive screens, increase cancer detection rates (CDRs), and address resourcing challenges faced by breast screening programs. We compared the accuracy of AI versus radiologists in real-world population breast cancer screening, and estimated potential impacts on CDR, recall and workload for simulated AI-radiologist reading. External validation of a commercially-available AI algorithm in a retrospective cohort of 108,970 consecutive mammograms from a population-based screening program, with ascertained outcomes (including interval cancers by registry linkage). Area under the ROC curve (AUC), sensitivity and specificity for AI were compared with radiologists who interpreted the screens in practice. CDR and recall were estimated for simulated AI-radiologist reading (with arbitration) and compared with program metrics. The AUC for AI was 0.83 compared with 0.93 for radiologists. At a prospective threshold, sensitivity for AI (0.67; 95% CI: 0.64-0.70) was comparable to radiologists (0.68; 95% CI: 0.66-0.71) with lower specificity (0.81 [95% CI: 0.81-0.81] versus 0.97 [95% CI: 0.97-0.97]). Recall rate for AI-radiologist reading (3.14%) was significantly lower than for the BSWA program (3.38%) (-0.25%; 95% CI:-0.31 to-0.18; P<0.001). CDR was also lower (6.37 versus 6.97 per 1000) (-0.61; 95% CI:-0.77 to-0.44; P<0.001); however, AI detected interval cancers that were not found by radiologists (0.72 per 1000; 95% CI: 0.57-0.90). AI-radiologist reading increased arbitration but decreased overall screen-reading volume by 41.4% (95% CI: 41.2-41.6). Replacement of one radiologist by AI (with arbitration) resulted in lower recall and overall screen-reading volume. There was a small reduction in CDR for AI-radiologist reading. AI detected interval cases that were not identified by radiologists, suggesting potentially higher CDR if radiologists were unblinded to AI findings. These results indicate AI's potential role as a screen-reader of mammograms, but prospective trials are required to determine whether CDR could improve if AI detection was actioned in double-reading with arbitration. National Breast Cancer Foundation (NBCF), National Health and Medical Research Council (NHMRC).

EBNEO commentary: Oral versus intravenous sildenafil for pulmonary hypertension in neonates.

Chetan C, Suryawanshi P, Patnaik A, Soni SB, Rath C, Pareek P, Gupta B, Garergrat RR, Verma A, Singh, Y. Oral versus intravenous sildenafil for pulmonary hypertension in neonates: a randomised trial. BMC Pediatr. 2022 May27; 22(1):311. DOI: 10.1186/s12887-022-03366-3. PMID: 35624452. Persistent pulmonary hypertension (PPHN) involves persistent pulmonary vascular resistance, which occurs in approximately 2 in every 1000 live infants.1 This is associated with sequelae, including chronic lung disease, neurodevelopmental complications, and death. The current well-understood management of PPHN includes inhaled nitric oxide (iNO), which is used as the first-line treatment of PPHN in higher-resourced countries.1 However, less-resourced countries have limited availability to iNO. There is some literature on other treatments, including sildenafil; however as recommended in the 2017 Cochrane review which evaluated five randomised clinical trials and several case reports that sildenafil has the potential to increase survival in neonates with PPHN, particularly in settings where iNO is not available.2 Subsequently, Chetan et al., at a single centre in a level III neonatal intensive care unit in an urban centre in India, developed an open labelled, parallel, randomised trial to determine if oral versus intravenous sildenafil have similar efficacy, safety, and response in the management of mild-to-moderate pulmonary hypertension in late preterm and term neonates. Pulmonary hypertension was defined as pulmonary arterial pressure (PAP) >25 mmHg on echocardiography within 72 h of birth. The primary outcome sought the time taken for PAP to <25 mmHg, comparing 6 hourly oral sildenafil 1 mg/kg/dose versus IV sildenafil given with a loading dose of 0.4 mg/kg of sildenafil over 3 h followed by continuous infusion of 1.6 mg/kg/day. Once treatment was started, echocardiograms were repeated every 12 h until PAP <25 mmHg and sildenafil were tapered within 4 days and stopped. Between February 2019 and December 2020, 40 infants were randomised in this study. Both groups had similar follow-up rates of 17/20 in the oral group and 15/20 in the IV group, and the sildenafil could be tapered after a median of 48 h in both groups. Complications of hypotension (n = 4) and reduced cardiac contractility (n = 1) were seen in the IV group requiring inotropes, compared to none in the oral group.3 Whilst there was no difference in the median time for sildenafil tapering between the two groups, this was in the context of 12 hourly echocardiograms. Perhaps, more frequent intervals of echocardiogram performed whilst on sildenafil may have found a difference between the two groups. This remains a small, unblinded trial with the clinicians managing the patients and performing the echocardiogram unblinded. Furthermore, the other limitations of this study were a small sample size of 40 babies which was not powered to detect a statistical or meaningful difference between the two preparations of sildenafil. Research directions could include a blinded, multicentre trial to increase further knowledge of the safety and efficacy of oral versus intravenous preparations of sildenafil in resource-limited settings. Whilst iNO will continue to be the first line, there may be scope to demonstrate sildenafil benefits as a dual therapy with iNO. Research performed in higher-resourced countries can lend further knowledge in this area. https://ebneo.org/ebneo-commentary-po-vs-iv-sildenafil-for-ph. AK receives funding from the Australian National Health and Medical Research Council (NHMRC) (APP1161379). The contents of this paper are solely the responsibility of the individual authors and do not reflect the views of the NHMRC. Open access publishing facilitated by The University of Adelaide, as part of the Wiley - The University of Adelaide agreement via the Council of Australian University Librarians. The authors have no conflicts of interest to declare.

Editorial introductions.

Editorial introductions.

EBNEO commentary: Maternal high-dose DHA supplementation and neurodevelopment in infants born before 29 weeks' gestation.

This was a planned follow-up study of the Canadian multicentre, randomised, double-blind, placebo-controlled superiority trial, Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck). Enrolment in the primary study occurred from 2015 to 2018. A total of 457 infants were included in the final analysis.1, 2 At 18–22 months' corrected age, neurodevelopmental outcomes as assessed by Bayley-III cognitive, language, and motor composite scores were not statistically significant between the treatment and placebo groups.1 The rates of death before 18–22 months' corrected age, cerebral palsy, hearing impairment and visual impairment were also not statistically significant between the two groups.1 Some aspects may bias study results towards the null. First, approximately half the infants in both groups received intravenous docosahexaenoic acid (DHA). This was on average for 21–23 days, in the form of DHA-rich lipids. Second, there may have been additional enteral DHA supplementation in both groups. At 6 weeks postmenstrual age, infants received a median of 130–133 mL/kg/day of expressed breast milk.1 This suggests that many infants at this age were receiving supplemental nutrition, such as donor breast milk or formula. Formula frequently contains DHA.3 The use of fortifier, which also contains DHA, was not commented on.4 The total fatty acid levels in breast milk at 14 days post-delivery were, on average, similar between the groups. In the treatment group DHA composed on average 0.97% of total fatty acids in breast milk at 14 days post-delivery, and in the placebo group, 0.35%.1 The authors note the hypothesis that sole DHA supplementation may cause an imbalance between the long-chain polyunsaturated fatty acids (LCPUFAs), potentially negating the benefits of high-dose DHA supplementation.1 Indeed, expert consensus statements recommend that preterm infants are supplemented with multiple LCPUFAs, such as DHA and arachidonic acid.4, 5 Due to the lower frequency of severe intraventricular haemorrhage (IVH) in the DHA group, a post hoc sensitivity analysis excluding participants with severe IVH was completed. This did not change the primary findings. Subgroup analysis found that for neonates born <27 weeks' gestation, those in the treatment group had a higher language score (mean difference 5.06, 95% CI 0.08–10.03; p = 0.05). This analysis was not adjusted for the imbalance in frequency of IVH.1 Further study limitations are well documented by the authors. This includes a suboptimal sample size limiting study interpretation, as enrolment for the MOBYDIck trial was terminated early due to concern that DHA was associated with bronchopulmonary dysplasia.1 Additionally, the sample size was chosen for the primary outcome of the MOBYDIck trial, and therefore has limited ability to detect differences in the primary outcome of this study. Despite the theoretical benefit of LCPUFA supplementation for preterm infants, several randomised controlled trials and a Cochrane systematic review have found little, if any, clinical neurodevelopmental effect.4, 6-9 This study is important as there is limited data on very preterm and extremely preterm infants. Based on this trial, maternal supplementation with high-dose DHA in breastfed infants born before 29 weeks' gestational age does not improve neurodevelopmental outcomes at 18–22 months' corrected age. URL LINK: https://ebneo.org/ebneo-commentary-maternal-dha-and-nd DV wrote the initial draft with AK providing key input. All authors revised the paper for critical scientific content. Open access publishing facilitated by The University of Adelaide, as part of the Wiley - The University of Adelaide agreement via the Council of Australian University Librarians. AK receives funding from the Australian National Health and Medical Research Council (NHMRC) (APP1161379). The contents of this paper are solely the responsibility of the individual authors and do not reflect the views of the NHMRC. The authors have no conflicts of interest to declare.

Principles for consumer involvement in health and medical research.

Principles for consumer involvement in health and medical research.

Phenome-wide Mendelian randomisation analysis identifies causal factors for age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the industrialised world and is projected to affect >280 million people worldwide by 2040. Aiming to identify causal factors and potential therapeutic targets for this common condition, we designed and undertook a phenome-wide Mendelian randomisation (MR) study. We evaluated the effect of 4591 exposure traits on early AMD using univariable MR. Statistically significant results were explored further using: validation in an advanced AMD cohort; MR Bayesian model averaging (MR-BMA); and multivariable MR. Overall, 44 traits were found to be putatively causal for early AMD in univariable analysis. Serum proteins that were found to have significant relationships with AMD included S100-A5 (odds ratio [OR] = 1.07, p-value = 6.80E-06), cathepsin F (OR = 1.10, p-value = 7.16E-05), and serine palmitoyltransferase 2 (OR = 0.86, p-value = 1.00E-03). Univariable MR analysis also supported roles for complement and immune cell traits. Although numerous lipid traits were found to be significantly related to AMD, MR-BMA suggested a driving causal role for serum sphingomyelin (marginal inclusion probability [MIP] = 0.76; model-averaged causal estimate [MACE] = 0.29). The results of this MR study support several putative causal factors for AMD and highlight avenues for future translational research. This project was funded by the Wellcome Trust (224643/Z/21/Z; 200990/Z/16/Z); the University of Manchester's Wellcome Institutional Strategic Support Fund (Wellcome ISSF) grant (204796/Z/16/Z); the UK National Institute for Health Research (NIHR) Academic Clinical Fellow and Clinical Lecturer Programmes; Retina UK and Fight for Sight (GR586); the Australian National Health and Medical Research Council (NHMRC) (1150144).

Guided Self-Help for People with Chronic Pain: Integrated Care in a Public Tertiary Pain Clinic-A Pilot Study.

Globally, chronic pain affects more than 30% of people worldwide and is the leading cause of disability and health care utilisation. Access to timely, person-centred, cost-effective programs is unattainable for most. People living in regional, rural and remote areas are disproportionately affected due to scarcity of services and qualified, multidisciplinary health and medical professionals. Caring and supporting people with chronic pain involves a range of interventions that incorporate a multifaceted bio-psychosocial approach. Tertiary and primary chronic pain services are optimally placed to deliver integrated models of care. This pilot study explored the effectiveness of an integrated Guided Self-Help (GSH) program within a multidisciplinary tertiary pain unit in a public hospital in Australia. A service delivery evaluation was undertaken and a pilot study implemented to determine feasibility and useability of an integrated GSH program for people with chronic pain. A single-group pre-post evaluation was provided to a convenience sample of 42 people referred to the Flinders Medical Centre Pain Management Unit (FMC PMU). Delivered via telehealth or in person by postgraduate students, a manualised GSH workbook was utilised to support adherence and fidelity. Content included goal setting, pain conceptualisation, psychoeducation, activity scheduling, pacing and cognitive strategies. The purpose of the integrated GSH pilot program was to support participants in gaining increased pain literacy, knowledge of effective physical and psychological strategies and enhance self-management of their chronic pain. Levels of psychological distress (PHQ-9 and GAD-7), pain catastrophising (PCS), and pain severity/interference (BPI) were assessed at the beginning and end of support. Integrating the program within a multidisciplinary pain unit intended to facilitate and provide participants with an understanding of their pain through a psychosocial lens, build self-efficacy, and recognise the benefits of other non-medical supports to manage their chronic pain in the future. Outcome data were routinely collected as part of FMC PMU usual practice for clinical and quality assurance purposes, then analysed retrospectively. Thus, under the National Health and Medical Research Council (NHMRC) Ethical Considerations in Quality Assurance and Evaluation Activities guidelines (NHMRC, 2014), and verified by the Southern Adelaide Local Health Network (SALHN) Research Committee (our institutional review board) via email (dated 10/09/2020), ethical review and approval were not required for this project as it constituted a quality improvement activity - specifically, a service delivery evaluation. This project is registered with the SALHN Quality Library (for quality assurance activities that are exempt from ethical approval) (Quality Register ID 3390). Participants showed statistically significant improvements on the PHQ-9 [i.e., mean drop of 2.85 (t = 3.16)], GAD [mean drop of 2.52 (t = 2.71)], and PCS [mean drop of 7.77 (t = 3.47)] with small-to-moderate effect sizes. BPI scores did not change. Results were similar when stratifying analyses by those who completed 2-5 versus 6-12 sessions. Integrating a GSH program for people with chronic pain into a multidisciplinary tertiary pain clinic is an efficacious and scalable way to increase access to effective strategies that can increase self-efficacy and self-management. Novel, scalable, and effective solutions are needed to improve quality of life and address disparities for people with chronic pain. The psychological shifts and benefits observed support efficacy towards self-management strategies that can increase autonomy and quality of life.

Factors associated with the uptake of national essential public health service package for hypertension and type-2 diabetes management in China's primary health care system: a mixed-methods study

China launched the primary health care (PHC) system oriented National Essential Public Health Service Package (NEPHSP) in 2009, to combat health challenges including the increasing burden from hypertension and type-2 diabetes (T2DM). In this study, the PHC system was assessed to understand factors influencing the uptake of the NEPHSP for hypertension and T2DM management. A mixed-methods study was conducted in seven counties/districts from five provinces across the mainland of China. Data included a PHC facility level survey and interviews with policy makers, health administrators, PHC providers, and individuals with hypertension and/or T2DM. The facility survey used the World Health Organisation (WHO) service availability and readiness assessment questionnaire. Interviews were thematically analysed using the WHO health systems building blocks. A total of 518 facility surveys were collected with over 90% in rural settings (n=474). Forty-eight in-depth individual interviews and 19 focus-group discussions were conducted across all sites. Triangulating the quantitative and qualitative data found that China's continuous political commitment to strengthening the PHC system led to improvements in workforce and infrastructure. Despite this, many barriers were identified, including insufficient and under-qualified PHC personnel, remaining gaps in medicines and equipment, fragmented health information systems, residents' low trust and utilization of PHC, challenges in coordinated and continuous care, and lack of cross-sectorial collaborations. The study findings provided recommendation for future PHC system strengthening, including improving the quality of NEPHSP delivery, facilitating resource-sharing across health facilities, establishing integrated care systems, and exploring mechanisms for better cross-sectorial engagement in health governance. The study is supported by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Disease funding (APP1169757).

Harnessing the nursing and midwifery workforce to boost Australia's clinical research impact.

Harnessing the nursing and midwifery workforce to boost Australia's clinical research impact.

Comparison of hip strength in football players with hip and/or groin-related pain and healthy controls

Introduction: Muscle weakness and atrophy have been associated with longstanding joint pathology, and strength testing is often recommended during the physical examination of patients with hip/groin pain. The aim of this study was to compare peak strength in football players (soccer and Australian football) presenting with hip and/or groin-related pain with healthy controls. Methods: Male and female football players were recruited across Melbourne and Brisbane, Australia. Demographic information and two questionnaires; the Copenhagen Hip and Groin Outcome Score (HAGOS) and the International Hip Outcome Tool 33 (iHOT) were collected. Hand-held dynamometry was utilised to test isometric hip muscle strength across flexion, extension, abduction, adduction, internal and external rotation planes. Peak strength (N) and torque (Nm) were normalised to body mass and linear mixed effects models were used to investigate the relationship between strength and symptomatic hips. Results: 191 football players with hip and/or groin-related pain (mean [+/- SD] age, 27.8 ± 6.3 years) and 69 controls (mean [+/- SD] age, 27.3 ± 5.6 years) were include in this study. Of this, 293 symptomatic hips and 138 control hips were used for analyses. Results demonstrated peak adduction (-0.18 Nm/kg: 95% CI -0.27 to -0.08, P 0.001), external rotation (-0.06 Nm/kg: 95% CI -0.09 to -0.02, P 0.003) and internal rotation strength (-0.06 Nm/kg: 95% CI -0.10 to -0.03, P 0.001) were lower in symptomatic hips than control hips. Abduction strength was lower in symptomatic Australian football players hips than controls (-0.20 Nm/kg: 95% CI -0.33 to -0.06, P 0.004) but this was not observed in symptomatic soccer players hips (-0.05 Nm/kg: 95% CI -0.15 to 0.06, P 0.382). No difference was found between peak flexion strength (0.07 Nm/kg: 95% CI -0.15 to 0.01, P 0.103) or peak extension strength (-0.07 Nm/kg: 95% CI -0.18 to 0.05, P 0.249) in symptomatic hips and control hips. Discussion: The findings from this research suggest that hip adduction, internal and external rotation are lower in footballers with hip and/or groin related pain than controls irrespective of the sport played. Hip abduction strength was lower in symptomatic Australian Rules football players but not observed in soccer. Impact:•Findings from this research suggest common impairments are found in hip adduction, internal and external rotation in football players with hip and/or groin related pain than controls regardless of sport played.•Hip abduction strength was lower in symptomatic Australian Rules football players but not observed in soccer. My co-authors and I acknowledge this research was supported by an Australian National Health and Medical Research Council (NHMRC) project grant 1088683.

Interventions to prevent obesity in school-aged children 6-18 years: An update of a Cochrane systematic review and meta-analysis including studies from 2015-2021.

BackgroundChildhood obesity remains a global public health priority due to the enormous burden it generates. Recent surveillance data suggests there has been a sharp increase in the prevalence of childhood obesity during the COVID-19 pandemic. The Cochrane review of childhood obesity prevention interventions (0–18 years) updated to 2015 is the most rigorous and comprehensive review of randomised controlled trials (RCTs) on this topic. A burgeoning number of high quality studies have been published since that are yet to be synthesised.MethodsAn update of the Cochrane systematic review was conducted to include RCT studies in school-aged children (6-18 years) published to 30 June 2021 that assessed effectiveness on child weight (PROSPERO registration: CRD42020218928). Available cost-effectiveness and adverse effect data were extracted. Intervention effects on body mass index (BMI) were synthesised in random effects meta-analyses by setting (school, after-school program, community, home), and meta-regression examined the association of study characteristics with intervention effect.FindingsMeta-analysis of 140 of 195 included studies (183,063 participants) found a very small positive effect on body mass index for school-based studies (SMD –0·03, 95%CI –0·06,–0·01; trials = 93; participants = 131,443; moderate certainty evidence) but not after-school programs, community or home-based studies. Subgroup analysis by age (6–12 years; 13–18 years) found no differential effects in any setting. Meta-regression found no associations between study characteristics (including setting, income level) and intervention effect. Ten of 53 studies assessing adverse effects reported presence of an adverse event. Insufficient data was available to draw conclusions on cost-effectiveness.InterpretationThis updated synthesis of obesity prevention interventions for children aged 6–18 years, found a small beneficial impact on child BMI for school-based obesity prevention interventions. A more comprehensive assessment of interventions is required to identify mechanisms of effective interventions to inform future obesity prevention public health policy, which may be particularly salient in for COVID-19 recovery planning.FundingThis research was funded by the National Health and Medical Research Council (NHMRC), Australia (Application No APP1153479).

HIV prevalence ratio of international migrants compared to their native-born counterparts: A systematic review and meta-analysis.

SummaryBackgroundPeople on the move, including international migrants, may face health inequities that expose them to a higher risk for HIV than native-born populations. We conducted a systematic review to calculate the HIV prevalence ratio of international migrants compared with native-born populations.MethodsWe searched five databases between January 2010 and March 2022. Using random-effects meta-analysis, we calculated the pooled HIV prevalence ratios (PR) by comparing the HIV prevalence of migrants with native-born populations. Our research protocol is registered in the International prospective register of systematic reviews (PROSPERO, CRD42021250867).FindingsIn total, 5,121 studies were screened, and 38 were included in the final analysis: 7,121,699 migrants and more than 270 million natives were included in the analysis. The pooled PR for any foreign-born migrants was 1·70 (95% CI 1·11 – 2·61, I2=99·67%, n = 33 studies), refugees was 2·37 (95% CI 0·33–16·99, I2=99·5%, n = 5), undocumented people was 3·98 (95% CI 0·11–143·01, I2=94·6%, n = 3), whilst asylum seekers was 54·79 (95% CI 17·23–174·23, I2=90·2%, n = 2). Meta-regression revealed that population type (adjusted R-squared 11.5%), region of origin (11.3%) and migrant type (10.8%) accounted for heterogeneity more than country-income (2.4%) and study setting (2.3%).InterpretationAlthough it was not possible to assess if HIV infection occurred in the country of origin or destination, the HIV prevalence ratio was higher among migrants than in native-born populations. Inclusive health policies and strategies for delivering HIV testing, prevention and treatment services for migrant populations tailored to their needs are urgently needed.FundingJ.J.O. and E.P.F.C. are supported by the Australian National Health and Medical Research Council (NHMRC) Emerging Leader Fellowship (GNT1193955 and GNT1172873, respectively).