Contemporary reproductive outcomes for patients with polycystic ovary syndrome: a retrospective observational study

Context Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility and may be associated with adverse pregnancy and neonatal outcomes. However, it is difficult to establish how much of this risk is due to PCOS and how much to obesity. Objective To determine the impact of PCOS upon fertility, pregnancy and neonatal outcomes. Design and setting Data were extracted from the Clinical Practice Research Datalink (CPRD), a longitudinal anonymized primary care research database in the UK. Patients with a diagnosis of PCOS were matched to controls (1:2) by age (+/-1 year), BMI (+/- 3 units) and CPRD practice. Standardised fertility ratios (SFR) before and after diagnosis (index date) were calculated. Rates of miscarriage, pre-eclampsia, gestational diabetes, premature delivery, delivery method and neonatal outcomes were compared. Results 9,068 women with PCOS matched study criteria. Prior to index date the SFR for patients with PCOS was 0.80 (95% CI 0.77-0.83); following index date it was 1.16 (1.12-1.20). The adjusted odds ratios (OR) for miscarriage (1.70; 1.56-1.84), pre-eclampsia (1.32; 1.16-1.49), gestational diabetes (1.41; 1.2-1.66) and premature delivery (1.25; 1.1-1.43) were all increased compared to controls. Of PCOS births, 27.7% were by Caesarean section compared with 23.7% of controls (1.13; 1.05-1.21). Infants born to mothers with PCOS had an increased risk of neonatal jaundice (1.20; 1.03-1.39) and respiratory complications (1.20; 1.06-1.37). Conclusions PCOS is associated with subfertility but fertility rates are restored to those of the background population following diagnosis. Pregnancy complications and adverse neonatal outcomes are more prevalent for women with PCOS independently of obesity

Co-creating a climate comic book: reflections on using comics in intergenerational research and engagement

The places where people live, work and spend leisure time are essential to their health and wellbeing. However, with climate change, these environments are changing. It is paramount that we understand older and younger people’s climate change perspectives, behaviours and visions for the future so that the places that matter to them can be shaped and managed effectively for health, wellbeing and sustainability.This article presents the case for using comic books to explore climate change with diverse intergenerational groups. The bilingual (Welsh/English) Climate Comic was created in South Wales, UK, as part of the ‘Understanding Older and Younger People’s PerspecTives and Imaginaries of Climate Change’ (OPTIC) project. From February to May 2023, 65 older and younger people took part in structured workshops where we used creative methods (games, collaging, comic creation, mobile and online interviews, storyboarding) to elicit intergenerational conversation, articulate intangible values and explore change. Workshops were audio-recorded, and stories were developed into a comic by illustrator Laura Sorvala. We also used comics as part of wider engagement and to stimulate ideas in a design sprint with interested groups.We discuss why comics are suited to exploring climate change with older and younger people, and the process we used to create the Climate Comic. We then reflect on the affordances and limitations of our approach and make recommendations for future research in this area. We hope that this work will stimulate others to consider using this adaptable and engaging art form for further research and engagement with younger and older people

Women with Polycystic Ovary Syndrome have an increased risk of major cardiovascular events: a population study

Context The effects of Polycystic Ovary Syndrome (PCOS) on cardiovascular morbidity and mortality are unclear. Objective To establish the relative risk of myocardial infarction (MI), stroke, angina, revascularization and cardiovascular mortality for women with PCOS. Design Data were extracted from the Clinical Practice Research Datalink Aurum database. Patients with PCOS were matched to controls (1:1) by age, body mass index (BMI) category and primary care practice. The primary outcome was the time to major adverse cardiovascular event (MACE); a composite endpoint incorporating MI, stroke, angina, revascularization and cardiovascular mortality. Secondary outcomes were the individual MACE endpoints. Results Of 219,034 with a diagnosis of PCOS, 174,660 (79.7%) met the eligibility criteria and were matched. Crude rates of the composite endpoint, MI, stroke, angina, revascularization and cardiovascular mortality were respectively 82.7, 22.7, 27.4, 32.8, 10.5 and 6.97 per 100,000 patient-years for cases, and 64.3, 15.9, 25.7, 19.8, 7.13 and 7.75 per 100,000 patient-years for controls. In adjusted cox proportional hazard models (CPHM), the hazard ratios [HR] were 1.26 (95% confidence interval=1.13-1.41), 1.38 (1.11-1.72), 1.60 (1.32-1.94) and 1.50 (1.08-2.07) for the composite outcome, MI, angina and revascularization, respectively. In a time-dependent CPHM, weight gain (HR 1.01 [1.00-1.01]), prior type 2 diabetes (T2DM) (HR 2.40 [1.76-3.30]) and social deprivation (HR 1.53 [1.11-2.11]) increased risk of progression to the composite endpoint. Conclusions The risk of incident MI, angina and revascularization is increased in young women with PCOS. Weight and T2DM are potentially modifiable risk factors amenable to intervention

Rising incidence, health resource utilization, and costs of polycystic ovary syndrome in the United Kingdom

Context: Trends in incidence of polycystic ovary syndrome (PCOS) and effects on health resource utilization are unclear. Objective: To describe trends in prevalence and incidence of PCOS in the United Kingdom. To establish healthcare resource use and associated costs. Methods: Data were extracted from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics databases. Point prevalence and incidence were calculated (2004-2020). Patients with PCOS were matched to controls (1:1) by age, body mass index, and primary care practice. Primary care contacts were assigned an average cost and prescription items assigned a net ingredient cost. Inpatient admissions and outpatient consultations were processed into healthcare resource groups and costed to the national tariff. Results: PCOS incidence increased from 1.22 per 1000 person years in 2004 to 1.77 (2012) and 2.20 (2019). Point prevalence increased from 1.02% (2004) to 2.2% (2012) and 3.5% (2020), and was highest in Asians. Mean contacts per person year (ppy) for patients with PCOS vs controls were 0.48 vs 0.29 for inpatients (P < .001), 3.81 vs 2.15 for outpatients (P < .001), and 6.43 vs 4.68 (P < .001) for primary care. Mean healthcare costs (ppy) were £837 vs £493 (P < .001) for inpatients, £444 vs £253 (P < .001) for outpatients, £157 vs £112 for primary care, and £109 vs £83 (P < .001) for primary care prescriptions. Total healthcare contacts ppy were 10.72 vs 7.11 (P < .001) and total associated costs £1546 vs £940 (P < .001). Conclusion: The incidence of PCOS has risen significantly. Health resource utilization and costs of PCOS are significantly greater than controls. Key Words: polycystic ovary syndrome, incidence, prevalence, costs and cost analysis, health resources, ethnicit

Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes

Context Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and subfertility, but the effects on mental health and child neurodevelopment are unclear. Objectives To determine if (1) there is an association between PCOS and psychiatric outcomes and (2) whether rates of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are higher in children of mothers with PCOS. Design Data were extracted from the Clinical Practice Research Datalink. Patients with PCOS were matched to two control sets (1:1) by age, body mass index, and primary care practice. Control set 2 was additionally matched on prior mental health status. Primary outcomes were the incidence of depression, anxiety, and bipolar disorder. Secondary outcomes were the prevalence of ADHD or ASD in the children. Results Eligible patients (16,986) were identified; 16,938 and 16,355 were matched to control sets 1 and 2, respectively. Compared with control set 1, baseline prevalence was 23.1% vs 19.3% for depression, 11.5% vs 9.3% for anxiety, and 3.2% vs 1.5% for bipolar disorder (P < 0.001). The hazard ratio for time to each endpoint was 1.26 (95% confidence interval 1.19 to 1.32), 1.20 (1.11 to 1.29), and 1.21 (1.03 to 1.42) for set 1 and 1.38 (1.30 to 1.45), 1.39 (1.29 to 1.51), and 1.44 (1.21 to 1.71) for set 2. The odds ratios for ASD and ADHD in children were 1.54 (1.12 to 2.11) and 1.64 (1.16 to 2.33) for set 1 and 1.76 (1.27 to 2.46) and 1.34 (0.96 to 1.89) for set 2. Conclusions PCOS is associated with psychiatric morbidity and increased risk of ADHD and ASD in their children. Screening for mental health disorders should be considered during assessment

Open drug discovery of anti-virals critical for Canada’s pandemic strategy

In the event of the current COVID-19 pandemic and in preparation for future pandemics, open science can support mission-oriented research and development, as well as commercialization. Open science shares skills and resources across sectors; avoids duplication and provides the basis for rapid and effective validation due to full transparency. It is a strategy that can adjust quickly to reflect changing incentives and priorities, because it does not rely on any one actor or sector. While eschewing patents, it can ensure high-quality drugs, low pricing, and access through existing regulatory mechanisms. Open science practices and partnerships decrease transaction costs, increase diversity of actors, reduce overall costs, open new, higher-risk/higher-impact approaches to research, and provide entrepreneurs freedom to operate and freedom to innovate. We argue that it is time to re-open science, not only in its now restricted arena of fundamental research, but throughout clinical translation. Our model and attendant recommendations map onto a strategy to accelerate discovery of novel broad-spectrum anti-viral drugs and clinical trials of those drugs, from first-in-human safety-focused trials to late stage trials for efficacy. The goal is to ensure low-cost and rapid access, globally, and to ensure that Canadians do not pay a premium for drugs developed from Canadian science

A trust approach for sharing research reagents

The core feature of trusts-holding property for the benefit of others-is well suited to constructing a research community that treats reagents as public goods

High-throughput and high-sensitivity N-Glycan profiling: A platform for biopharmaceutical development and disease biomarker discovery

Protein glycosylation contributes to critical biological function of glycoproteins. Glycan analysis is essential for the production of biopharmaceuticals as well as for the identification of disease biomarkers. However, glycans are highly heterogeneous, which has considerably hampered the progress of glycomics. Here, we present an improved 96-well plate format platform for streamlined glycan profiling that takes advantage of rapid glycoprotein denaturation, deglycosylation, fluorescent derivatization, and on-matrix glycan clean-up. This approach offers high sensitivity with consistent identification and quantification of diverse N-glycans across multiple samples on a high-throughput scale. We demonstrate its capability for N-glycan profiling of glycoproteins from various sources, including two recombinant monoclonal antibodies produced from Chinese Hamster Ovary cells, EG2-hFc and rituximab, polyclonal antibodies purified from human serum, and total glycoproteins from human serum. Combined with the complementary information obtained by sequential digestion from exoglycosidase arrays, this approach allows the detection and identification of multiple N-glycans in these complex biological samples. The reagents, workflow, and Hydrophilic interaction liquid chromatography with fluorescence detection (HILIC-FLD), are simple enough to be implemented into a straightforward user-friendly setup. This improved technology provides a powerful tool in support of rapid advancement of glycan analysis for biopharmaceutical development and biomarker discovery for clinical disease diagnosis

Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis

Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific “immune fingerprints” may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis