Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline. DESIGN: Systematic review and meta-analysis of the literature. PATIENTS: Women with PCOS and treatment with insulin sensitisers. MEASUREMENTS: Hormonal and clinical outcomes, as well as side effects. RESULTS: Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m2 ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations. CONCLUSIONS: Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.

Machine Learning Algorithms Versus Classical Regression Models in Pre-Eclampsia Prediction: A Systematic Review.

PURPOSE OF REVIEW: Machine learning (ML) approaches are an emerging alternative for healthcare risk prediction. We aimed to synthesise the literature on ML and classical regression studies exploring potential prognostic factors and to compare prediction performance for pre-eclampsia. RECENT FINDINGS: From 9382 studies retrieved, 82 were included. Sixty-six publications exclusively reported eighty-four classical regression models to predict variable timing of onset of pre-eclampsia. Another six publications reported purely ML algorithms, whilst another 10 publications reported ML algorithms and classical regression models in the same sample with 8 of 10 findings that ML algorithms outperformed classical regression models. The most frequent prognostic factors were age, pre-pregnancy body mass index, chronic medical conditions, parity, prior history of pre-eclampsia, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and pregnancy-associated plasma protein A. Top performing ML algorithms were random forest (area under the curve (AUC) = 0.94, 95% confidence interval (CI) 0.91-0.96) and extreme gradient boosting (AUC = 0.92, 95% CI 0.90-0.94). The competing risk model had similar performance (AUC = 0.92, 95% CI 0.91-0.92) compared with a neural network. Calibration performance was not reported in the majority of publications. ML algorithms had better performance compared to classical regression models in pre-eclampsia prediction. Random forest and boosting-type algorithms had the best prediction performance. Further research should focus on comparing ML algorithms to classical regression models using the same samples and evaluation metrics to gain insight into their performance. External validation of ML algorithms is warranted to gain insights into their generalisability.

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

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION: The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS: This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS: The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.

The value of maternity care in Queensland, 2012-18, based on an analysis of administrative data: a retrospective observational study.

OBJECTIVE: To quantify the value of maternity health care - the relationship of outcomes to costs - in Queensland during 2012-18. STUDY DESIGN: Retrospective observational study; analysis of Queensland Perinatal Data Collection data linked with the Queensland Health Admitted Patient, Non-Admitted Patient, and Emergency Data Collections, and with the Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) databases. SETTING, PARTICIPANTS: All births in Queensland during 1 July 2012 - 30 June 2018. MAIN OUTCOME MEASURES: Maternity care costs per birth (reported in 2021-22 Australian dollars), both overall and by funder type (public hospital funders, MBS, PBS, private health insurers, out-of-pocket costs); value of care, defined as total cost per positive birth outcome (composite measure). RESULTS: The mean cost per birth (all funders) increased from $20 471 (standard deviation [SD], $17 513) during the second half of 2012 to $30 000 (SD, $22 323) during the first half of 2018; the annual total costs for all births increased from $1.31 billion to $1.84 billion, despite a slight decline in the total number of births. In a mixed effects linear analysis adjusted for demographic, clinical, and birth characteristics, the mean total cost per birth in the second half of 2018 was $9493 higher (99.9% confidence interval, $8930-10 056) than during the first half of 2012. The proportion of births that did not satisfy our criteria for a positive birth outcome increased from 27.1% (8404 births) during the second half of 2012 to 30.5% (9041 births) during the first half of 2018. CONCLUSION: The costs of maternity care have increased in Queensland, and many adverse birth outcomes have become more frequent. Broad clinical collaboration, effective prevention and treatment strategies, as well as maternal health services focused on all dimensions of value, are needed to ensure the quality and viability of maternity care in Australia.

Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review.

Cystic fibrosis is a monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which transports chloride ions in secretory organs. Modulator therapies are small molecules that correct CFTR dysfunction and can lead to a wide range of benefits for both pulmonary and extrapulmonary complications of cystic fibrosis. With advancements in airway, antimicrobial and nutritional therapies and now introduction of modulator therapies, most people living with cystic fibrosis in Australia are now adults. For adults with cystic fibrosis, endocrine manifestations such as cystic fibrosis-related diabetes, metabolic bone disease, and reproductive health are becoming increasingly important, and emerging evidence on the endocrine effects of CFTR modulator therapies is promising and is shifting paradigms in our understanding and management of these conditions. The management of cystic fibrosis-related diabetes will likely need to pivot for high responders to modulator therapy with dietary adaptions and potential use of medications traditionally reserved for adults with type 2 diabetes, but evidence to support changing clinical care needs is currently lacking. Increased attention to diabetes-related complications screening will also be required. Increased exercise capacity due to improved lung function, nutrition and potentially direct modulator effect may have a positive impact on cystic fibrosis-related bone disease, but supporting evidence to date is limited. Fertility can improve in women with cystic fibrosis taking modulator therapy. This has important implications for pregnancy and lactation, but evidence is lacking to guide pre-conception and antenatal management. Provision of multidisciplinary clinical care remains ever-important to ensure the emergence of endocrine and metabolic complications are optimised in adults with cystic fibrosis.

Menstrual cycle regularity as a predictor for heart disease and diabetes: Findings from a large population-based longitudinal cohort study.

OBJECTIVE: Menstrual cycle regularity underpins the diagnosis of polycystic ovary syndrome (PCOS), which is linked to adverse cardio-metabolic profile. However, links between menstrual disorders and metabolic conditions are often under-appreciated and not considered when assessing cardio-metabolic risk in women. We aimed to assess the risk of diabetes and heart disease in women with irregular menstrual cycles and those whose cycles were regular. METHODS: This was a community based longitudinal cohort study. We utilized the 1946 to 1951 birth cohort database (N = 13,714) of the Australian Longitudinal Study on Women's Health (ALSWH) over a 20-year follow-up period. Data were analysed using Cox regression models. RESULTS: Women with irregular menstrual cycles had 20% higher risk of developing heart disease [adjusted hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01-1.43) compared with those with regular menstrual cycles. We also observed 17% higher risk of diabetes (HR: 1.17, 95% CI: 1.00-1.38) in women who had irregular menstrual cycles than in women who had regular menstrual cycles. The diabetes risk was 30% higher (HR: 1.30, 95% CI: 1.09-1.55) if women had irregular cycles and did not use hormone replacement therapy, but this was not significant on adjustment for all covariates. CONCLUSION: Having irregular menstrual cycles appears to be an early indicator for heart disease and diabetes. These findings suggest that irregular cycles among women in their forties may be linked to adverse cardio-metabolic outcomes. These women may benefit from screening and prevention strategies as recommended by related guidelines such as the international evidence-based guideline for the assessment and management of PCOS.

Natural history of polycystic ovary syndrome: A systematic review of cardiometabolic outcomes from longitudinal cohort studies.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have a worsened metabolic profile but the progression of cardiometabolic features over time is unclear. Understanding this natural history is a key priority in PCOS research and vital for guiding the prevention and management of this common condition. We explored cardiometabolic changes that are observed in women with PCOS compared to those without PCOS across the life course. DESIGN, PATIENTS AND MEASUREMENTS: A systematic review of longitudinal cohort studies was conducted across MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews between 15 January 2020 and 11 February 2021. Eligible studies included participants with or without PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) criteria. We included studies that were published from the year 1990 to 2021 with data on cardiometabolic outcomes as per the PCOS core outcomes set. RESULTS: There were 31 longitudinal studies with 28,316 participants from four continents. At the start of follow up, participants were aged between 1 year and 49 years with a follow-up period ranging from 2 to 32 years. Changes in BMI and the risk of coronary heart disease were similar in adult women with and without PCOS. Women with PCOS had a higher risk of Type 2 diabetes than their non-PCOS counterparts. Evidence for the majority of all other outcomes was conflicting and with inadequate data. CONCLUSION: Understanding the natural history of PCOS and particularly changes in cardiometabolic features remains challenging. Existing literature is extensive but heterogeneous and inconsistent. Longitudinal studies in unselected populations are needed to provide high-quality data in this area.

Clinical management of pregnancy in women with polycystic ovary syndrome: An expert opinion.

Polycystic ovary syndrome (PCOS) is associated with a higher risk for pregnancy and birth complications according to the specific features associated with PCOS. The features include obesity before and during pregnancy, hyperandrogenism, insulin resistance, infertility, cardiometabolic risk factors, and poor mental health. PCOS is not often recognized as a risk factor for poor pregnancy and birth outcomes in pregnancy care guidelines, while its associated features are. Pregnancy-related risk profile should ideally be assessed for modifiable risk factors (e.g., lifestyle and weight management) at preconception in women with PCOS. Hyperglycaemia should be screened using a 75-g oral glucose tolerance test at preconception or within the first 20 weeks of pregnancy if it has not been performed at preconception and should be repeated at 24-28 weeks of pregnancy. In the absence of evidence of benefit for strategies specific to women with PCOS, the international evidence-based guidelines for the assessment and management of PCOS recommend screening, optimizing, and monitoring risk profile in women with PCOS (at preconception, during and postpregnancy) consistent with the recommendations for the general population. Recommended factors include blood glucose, weight, blood pressure, smoking, alcohol, diet, exercise, sleep and mental health, emotional, and sexual health among women with PCOS. The guidelines recommend Metformin in addition to lifestyle for assisting with weight management and improving cardiometabolic risk factors, particularly in those with overweight or obesity. Letrozole is considered the first-line pharmacological treatment for anovulatory infertility in PCOS. Individualized approach should be considered in the management of pregnancy in PCOS.

Where are we in understanding the natural history of polycystic ovary syndrome? A systematic review of longitudinal cohort studies.

STUDY QUESTION: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course? SUMMARY ANSWER: Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS. WHAT IS KNOWN ALREADY: The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research. STUDY DESIGN, SIZE, DURATION: This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information. LIMITATIONS, REASONS FOR CAUTION: There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations. STUDY FUNDING/COMPETING INTEREST(S): This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women's Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare. REGISTRATION NUMBER: Prospero registration number: CRD42020165546.

Assessing the Content and Quality of Digital Tools for Managing Gestational Weight Gain: Systematic Search and Evaluation.

BACKGROUND: Digital health resources have the potential to assist women in optimizing gestational weight gain (GWG) during pregnancy to improve maternal health outcomes. OBJECTIVE: In this study, we aimed to evaluate the quality and behavior change potential of publicly available digital tools (websites and apps) that facilitate GWG tracking. METHODS: Digital tools were identified using key search terms across website search engines and app stores and evaluated using the Mobile App Rating Scale, the App Behavior Change Scale, as well as criteria to evaluate the rigor and safety of GWG information. RESULTS: Overall, 1085 tools were screened for inclusion (162 websites and 923 apps), and 19 were deemed eligible. The mean Mobile App Rating Scale quality score was 3.31 (SD 0.53) out of 5, ranging from 2.26 to 4.39, and the mean App Behavior Change Scale score was 6 (SD 3.4) out of 21, ranging from 19 to 0. Of the 19 items used to evaluate rigor of GWG advice, most tools (n=11, 57.9%) contained ≤3 items. CONCLUSIONS: This review emphasizes the substantial limitations in current digital resources promoting the monitoring and optimization of GWG. Most tools were of low quality, had minimal behavior change potential, and were potentially unsafe, with minimal linkage to evidence-based information or partnership with health care.

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.

Predictors of hypertensive disorders in pregnancy in women with and without polycystic ovary syndrome: The Australian Longitudinal Study of Women's Health.

OBJECTIVES: A higher risk of hypertensive disorders in pregnancy (HDP) is frequently reported in women with polycystic ovary syndrome (PCOS). These women, however, have a higher risk profile for HDP compared with women without PCOS. The aim of this study was to elucidate the impact of PCOS per se on the incidence of HDP through post hoc subgroup analyses of the Australian Longitudinal Study on Women's Health by level of risk. DESIGN: Longitudinal study. PATIENTS: Of a total of 14,247 participants, 5838 women met the inclusion criteria. Eligible women were required to report PCOS and HDP status in at least one pregnancy within the study. MEASUREMENTS: Included risk factors were age, body mass index, country of birth, parity, multiple pregnancy, subfertility, infertility treatment (hormonal vs. in vitro fertilization), gestational diabetes (GDM), family history of GDM and socioeconomic status. Longitudinal association between PCOS and HDP was assessed the using Cox proportional hazard regression with Efron's method. RESULTS: While PCOS was associated with a higher incidence of HDP in a univariate model [hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.05, 1.72], the significance was not retained after adjustment for risk factors [HR: 1.19, 95% CI: 0.79, 1.79]. However in multivariate analysis of subgroups, PCOS remained significantly associated with higher risk of HDP in non-obese women only [HR: 1.77, 95% CI: 1.11, 2.82]. CONCLUSIONS: Higher risk of HDP in PCOS is likely related to risk factors other than PCOS.

Weight gain and lifestyle factors in women with and without polycystic ovary syndrome.

STUDY QUESTION: Do extrinsic factors including lifestyle, psychosocial factors and healthcare professional engagement independently contribute to weight gain in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS had a higher rate of weight gain than women without PCOS which was most marked in those with unhealthy lifestyles. WHAT IS KNOWN ALREADY: Women with PCOS have a higher prevalence of overweight/obesity and greater weight gain than women without PCOS. The association of lifestyle factors with weight change in PCOS is not known. STUDY DESIGN, SIZE, DURATION: The study was a population-based observational study with data collected from seven surveys over 19 years (N = 14 127; Survey 1) involving women with and without PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used data from the 1973-1978 birth cohort of the Australian Longitudinal Study on Women's Health. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS gained more weight annually (0.26 kg/year; 95% CI 0.12, 0.39; P < 0.0001) and over 19 years (4.62 kg; 95% CI 3.04, 6.21; P < 0.0001) than women without PCOS (adjusted analyses). For all women, there were positive associations between weight gain and energy intake, sitting time and stress; inverse associations with fibre intake and physical activity (PA); and no associations with diet quality, glycaemic index, healthcare utilization, depression or anxiety. There were interactions between lifestyle factors (energy intake P = 0.006, glycaemic index P = 0.025, sitting time P = 0.041 and PA P = 0.021), PCOS status and time such that weight gain varied between women with and without PCOS according to these factors. LIMITATIONS, REASONS FOR CAUTION: The limitations of this study include the use of self-reported measures such as diet, PA, sitting time, psychological factors and health care utilization. WIDER IMPLICATIONS OF THE FINDINGS: While women with PCOS are more prone to weight gain, lifestyle factors have a more profound impact on weight gain in women with PCOS than without PCOS. These study findings have implications for understanding the mechanisms of weight gain in women with PCOS. They also highlight the importance of early lifestyle intervention as soon as PCOS is diagnosed to address modifiable extrinsic factors and prevent excess weight gain and worsening of the clinical features of PCOS. STUDY FUNDING/COMPETING INTEREST(S): M.A.A. is funded by the Monash International Tuition Scholarship and Monash Graduate Scholarship and L.J.M. is funded by a National Heart Foundation Future Leader Fellowship. The authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Facilitators and barriers to behaviour change within a lifestyle program for women with obesity to prevent excess gestational weight gain: a mixed methods evaluation.

BACKGROUND: Maternal obesity is associated with health risks for women and their babies and is exacerbated by excess gestational weight gain. The aim of this study was to describe women's experiences and perspectives in attending a Healthy Pregnancy Service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. METHODS: An explanatory sequential mixed methods study design utilised two questionnaires (completed in early and late pregnancy) to quantify feelings, motivation and satisfaction with the service, followed by semi-structured interviews that explored barriers and enablers of behaviour change. Data were analysed separately and then interpreted together. RESULTS: Overall, 49 women attending the service completed either questionnaire 1, 2 or both and were included in the analysis. Fourteen women were interviewed. Prior to pregnancy, many women had gained weight and attempted to lose weight independently, and reported they were highly motivated to achieve a healthy lifestyle. During pregnancy, diet changes were reported as easier to make and sustain than exercise changes. Satisfaction with the service was high. Key factors identified in qualitative analysis were: service support enabled change; motivation to change behaviour, social support, barriers to making change (intrinsic, extrinsic and clinic-related), post-partum lifestyle and needs. On integration of data, qualitative and quantitative findings aligned. CONCLUSIONS: The Healthy Pregnancy service was valued by women. Barriers and enablers to the delivery of an integrated model of maternity care that supported healthy lifestyle and recommended gestational weight gain were identified. These findings have informed and improved implementation and further scale up of this successful service model, integrating healthy lifestyle into routine antenatal care of women with obesity. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (no.12620000985987). Registration date 30/09/2020, retrospectively registered. http://www.anzctr.org.au/.

Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood.

BACKGROUND: Polycystic ovary syndrome (PCOS) is challenging to diagnose. While the 2003 Rotterdam criteria are widely used for adults, the 2018 international PCOS guideline recommended updated Rotterdam criteria with both hyperandrogenism and oligo-anovulation for adolescents based on evidence-informed expert consensus. This study compared the prevalence of PCOS using updated and original Rotterdam criteria in community-based adolescents and explored long-term body mass index (BMI) trajectories across different diagnostic phenotypes. METHODS: Overall, 227 postmenarchal adolescent females from the prospective cohort Raine Study undertook comprehensive PCOS assessment at age 14-16 years. Detailed anthropometric measurements were collected from birth until age 22 years. Cross-sectional and longitudinal BMI were analyzed using t tests and generalized estimating equations. RESULTS: PCOS was diagnosed in 66 (29.1%) participants using original criteria versus 37 (16.3%) participants using updated Rotterdam criteria. Using updated criteria, participants with PCOS had higher BMI than participants without PCOS from prepubertal. Only the phenotype meeting the updated criteria was significantly associated with higher long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories to participants without PCOS (p < 0.001). CONCLUSIONS: The use of the 2018 updated Rotterdam criteria reduces over-diagnosis of PCOS in adolescents and identifies those at the greatest risk of long-term weight gain, a key contributor to disease severity and long-term health implications. The BMI trajectories of females with PCOS on updated criteria diverge prepubertally compared to those without PCOS. This work supports targeting adolescents diagnosed with PCOS on the 2018 updated criteria for early lifestyle interventions to prevent long-term health complications.

Curtailing PCOS.

Polycystic ovary syndrome (PCOS), characterized by hormonal imbalance and ovarian dysfunction, often starts during adolescence. Inconsistent diagnostic criteria, variable provider knowledge, and lack of consensus pose specific challenges for the care of women with PCOS. These factors encourage inaccurate diagnosis with both under and overdiagnosis. This unfavorable diagnostic experience exasperates affected women and limits timely opportunities for intervention to minimize associated comorbidities, especially during the transition from pediatric to adult care. Recognition of these issues in the care of adolescents and women with PCOS inspired the development of the International Evidence-Based PCOS Guidelines, which emphasize the prevention, screening, and treatment of PCOS across the reproductive lifespan. The Guidelines and accompanying meta-analyses focus on three major categories of associated comorbidities: (1) reproductive; (2) metabolic; and (3) psychological. With the exception of infertility, this article considers common manifestations and comorbidities associated with PCOS throughout the lifecycle. Healthy lifestyle interventions with prevention of excess weight gain comprise the primary intervention for all comorbidities. Hence, early identification of girls "at risk" for PCOS and those with PCOS is a priority. Extensive guidelines for provider and patient education aim to decrease the medical, psychosocial, and economic burdens attributable to PCOS and its associated comorbidities.

Leaders' perspectives on learning health systems: a qualitative study.

BACKGROUND: Integrated utilisation of digital health data has the power to transform healthcare to deliver more efficient and effective services, and the learning health system (LHS) is emerging as a model to achieve this. The LHS uses routine data from service delivery and patient care to generate knowledge to continuously improve healthcare. The aim of this project was to explore key features of a successful and sustainable LHS to inform implementation in an Academic Health Science Centre context. METHODS: We purposively identified and conducted semi-structured qualitative interviews with leaders, experienced in supporting or developing data driven innovations in healthcare. A thematic analysis using NVivo was undertaken. RESULTS: Analysis of 26 interviews revealed five themes thought to be integral in an effective, sustainable LHS: (1) Systematic approaches and iterative, continuous learning with implementation into healthcare contributing to new best-practice care; (2) Broad stakeholder, clinician and academic engagement, with collective vision, leadership, governance and a culture of trust, transparency and co-design; (3) Skilled workforce, capability and capacity building; (4) Resources with sustained investment over time and; (5) Data access, systems and processes being integral to a sustainable LHS. CONCLUSIONS: This qualitative study provides insights into the elements of a sustainable LHS across a range of leaders in data-driven healthcare improvement. Fundamentally, an LHS requires continuous learning with implementation of new evidence back into frontline care to improve outcomes. Structure, governance, trust, culture, vision and leadership were all seen as important along with a skilled workforce and sustained investment. Processes and systems to optimise access to quality data were also seen as vital in an effective, sustainable LHS. These findings will inform a co-designed framework for implementing a sustainable LHS within the Australian healthcare and Academic Health Science Centre context. It is anticipated that application of these findings will assist to embed and accelerate the use of routine health data to continuously generate new knowledge and ongoing improvement in healthcare delivery and health outcomes.

Perinatal Distress During COVID-19: Thematic Analysis of an Online Parenting Forum.

BACKGROUND: The COVID-19 global pandemic has impacted the whole of society, requiring rapid implementation of individual-, population-, and system-level public health responses to contain and reduce the spread of infection. Women in the perinatal period (pregnant, birthing, and postpartum) have unique and timely needs for directives on health, safety, and risk aversion during periods of isolation and physical distancing for themselves, their child or children, and other family members. In addition, they are a vulnerable group at increased risk of psychological distress that may be exacerbated in the context of social support deprivation and a high-risk external environment. OBJECTIVE: The aim of this study is to examine the public discourse of a perinatal cohort to understand unmet health information and support needs, and the impacts on mothering identity and social dynamics in the context of COVID-19. METHODS: A leading Australian online support forum for women pre- through to postbirth was used to interrogate all posts related to COVID-19 from January 27 to May 12, 2020, inclusive. Key search terms included "COVID," "corona," and "pandemic." A three-phase analysis was conducted, including thematic analysis, sentiment analysis, and word frequency calculations. RESULTS: The search yielded 960 posts, of which 831 were included in our analysis. The qualitative thematic analysis demonstrated reasonable understanding, interpretation, and application of relevant restrictions in place, with five emerging themes identified. These were (1) heightened distress related to a high-risk external environment; (2) despair and anticipatory grief due to deprivation of social and family support, and bonding rituals; (3) altered family and support relationships; (4) guilt-tampered happiness; and (5) family future postponed. Sentiment analysis revealed that the content was predominantly negative (very negative: n=537 and moderately negative: n=443 compared to very positive: n=236 and moderately positive: n=340). Negative words were frequently used in the 831 posts with associated derivatives including "worried" (n=165, 19.9%), "risk" (n=143, 17.2%), "anxiety" (n=98, 11.8%), "concerns" (n=74, 8.8%), and "stress" (n=69, 8.3%). CONCLUSIONS: Women in the perinatal period are uniquely impacted by the current pandemic. General information on COVID-19 safe behaviors did not meet the particular needs of this cohort. The lack of nuanced and timely information may exacerbate the risk of psychological and psychosocial distress in this vulnerable, high-risk group. State and federal public health departments need to provide a central repository of information that is targeted, consistent, accessible, timely, and reassuring. Compensatory social and emotional support should be considered, using alternative measures to mitigate the risk of mental health disorders in this cohort.

Brown adipose tissue thermogenesis in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with increased obesity with a greater propensity to weight gain and a lack of sustainable lifestyle interventions. Altered brown adipose tissue (BAT) thermogenesis is a potential contributor to obesity in PCOS. BAT activity and modulation have not been studied in PCOS. This observational study explored BAT thermogenesis and its associations in women with and without PCOS. PARTICIPANTS AND METHODS: Cutaneous temperature was recorded from supraclavicular (indicator of BAT activity) and upper arm regions using dataloggers (SubCue, Calgary, Canada) in a cross-sectional substudy, nested within a randomized control trial, of community-recruited premenopausal women with (n = 47, Rotterdam diagnostic criteria) and without (n = 11) PCOS. RESULTS: Complete temperature data were available in 44 PCOS (mean age: 30.0 ± 6.2, mean BMI: 29.3 ± 5.5) and 11 non-PCOS (mean age: 33.0 ± 7.0, mean BMI: 25 ± 3) women. Women with PCOS had lower supraclavicular skin temperature compared to controls overall (33.9 ± 0.7 vs 34.5 ± 1, P < 0.05) and during sleep (34.5 ± 0.6 vs 35.2 ± 0.9, P < 0.001). In the PCOS group, supraclavicular skin temperature overall and over sleep and waking hours correlated inversely with testosterone (r = -0.41 P < 0.05, r = -0.485 P < 0.01 and r = -0.450 P < 0.01 respectively). Testosterone levels explained approximately 15%, 30% and 20% of the variability in supraclavicular skin temperature overall and over sleep and waking hours in women with PCOS, respectively. CONCLUSION: Women with PCOS have lower BAT activity compared to controls. BAT thermogenesis is negatively associated with androgen levels in PCOS.