Comprehensive observational study evaluating the enduring effectiveness of 4CMenB, the meningococcal B vaccine against gonococcal infections in the Northern Territory and South Australia, Australia: study protocol.

INTRODUCTION: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. METHODS AND ANALYSES: This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. ETHICS AND DISSEMINATION: The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.

A systematic review and meta-analysis of the diagnosis and surgical management of carcinoid heart disease.

Introduction: Carcinoid heart disease (CHD), a complication of carcinoid syndrome (CS), is a rare condition that can lead to right sided valvular heart disease and has been traditionally associated with a poor prognosis. We conducted a systematic review and meta-analysis to explore the accuracy of biomarkers and echocardiography in diagnosing CHD amongst patients who are already known to have neuroendocrine tumours and to assess whether surgical management of CHD leads to a reduction in mortality. Methods: A systematic literature search of MEDLINE, EMBASE, EBM Reviews, Google Scholar, ClinicalTrials.gov was conducted. All studies on patients with carcinoid heart disease (CHD) reporting on biomarkers, echocardiographic and surgical outcomes were included. The National Heart, Lung, and Blood Institute quality assessment tool was used to assess the methodological study quality. Data analysis was performed using Stata Statistical Software and R Studio, and individual meta-analyses were performed for biomarkers, echocardiographic findings, and surgical outcomes. Results: A total of 36 articles were included in the systematic review analysis. N terminal pro-brain natriuretic peptide (NTproBNP) and 5-hydroxyindole acetate (5-HIAA) levels were higher in patients with CHD compared with those without CHD. 32% of CS patients had echocardiographic evidence of cardiac involvement, of which 79% involved tricuspid valve abnormalities. Moderate-severe tricuspid regurgitation was the most common echocardiographic abnormality (70% of patients). However, these analyses had substantial heterogeneity due to the high variability of cardiac involvement across studies. Pooled surgical mortality for CHD was 11% at 1 month, 31% at 12 months and 56% at 24 months. When assessing surgical outcomes longitudinally, the one-month surgical results showed a trend towards more recent surgeries having lower mortality rates than those reported in earlier years, however this was not statistically significant. Discussion: There is not enough data in current literature to determine a clear cut-off value of NTproBNP and 5-HIAA to help diagnose or determine CHD severity. Surgical management of CHD is yet to show significant mortality benefit, and there are no consistent comparisons to medical treatment in current literature.

Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children: EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics.

INTRODUCTION: Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive 'nudge' interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children. METHODS AND ANALYSES: Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake. ETHICS AND DISSEMINATION: The protocol and study documents have been reviewed and approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums. TRIAL REGISTRATION NUMBER: NCT05613751.

Modifiable and Non-Modifiable Risk Factors for Premature Coronary Heart Disease (PCHD): Systematic Review and Meta-Analysis.

AIM: We aimed to compare the prevalence of modifiable and non-modifiable coronary heart disease (CHD) risk factors among those with premature CHD and healthy individuals. METHODS: PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol is registered in PROSPERO CRD42020173216). The quality of studies was assessed using the National Heart, Lung and Blood Institute tool for cross-sectional, cohort and case-control studies. Meta-analyses were performed using Review Manager 5.3. Effect sizes for categorical and continuous variables, odds ratio (OR) and mean differences (MD)/standardised mean differences (SMD) with 95% confidence intervals (CI) were reported. RESULTS: A total of n=208 primary studies were included in this review. Individuals presenting with premature CHD (PCHD, age ≤65 years) had higher mean body mass index (MD 0.54 kg/m2, 95% CI 0.24, 0.83), total cholesterol (SMD 0.27, 95% CI 0.17, 0.38), triglycerides (SMD 0.50, 95% CI 0.41, 0.60) and lower high-density lipoprotein cholesterol (SMD 0.79, 95% CI: -0.91, -0.68) compared with healthy individuals. Individuals presenting with PCHD were more likely to be smokers (OR 2.88, 95% CI 2.51, 3.31), consumed excessive alcohol (OR 1.40, 95% CI 1.05, 1.86), had higher mean lipoprotein (a) levels (SMD 0.41, 95% CI 0.28, 0.54), and had a positive family history of CHD (OR 3.65, 95% CI 2.87, 4.66) compared with healthy individuals. Also, they were more likely to be obese (OR 1.59, 95% CI 1.32, 1.91), and to have had dyslipidaemia (OR 2.74, 95% CI 2.18, 3.45), hypertension (OR 2.80, 95% CI 2.28, 3.45), and type 2 diabetes mellitus (OR 2.93, 95% CI 2.50, 3.45) compared with healthy individuals. CONCLUSION: This meta-analysis confirms current knowledge of risk factors for PCHD, and identifying these early may reduce CHD in young adults.

Influence of Socioeconomic Status on the Association Between Pregnancy Complications and Premature Coronary Artery Disease: Linking Three Cohorts.

Background: We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk. Materials and Methods: This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case-control study design. Cases (n = 721), that is, women aged <60 years from Coronary Angiogram Database of South Australia (CADOSA) were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain prior pregnancy outcomes and SES. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS), comprising women who were healthy or had health conditions unrelated to CAD, age matched to CADOSA (±5 years), and linked to SAPSC to determine prior pregnancy outcomes and SES. This project performed comparative analysis of SES using socioeconomic indexes for areas-index of relative socioeconomic advantage and disadvantage (SEIFA-IRSAD) scores across three databases. Results: Findings revealed that SEIFA-IRSAD scores at the time of pregnancy (p-value = 0.005) and increase in SEIFA-IRSAD scores over time (p-value = 0.040) were significantly associated with PCAD. In addition, when models were adjusted for SEIFA-IRSAD scores at the time of pregnancy and age, risk factors including placenta-mediated pregnancy complications such as preterm birth (odds ratio [OR] = 4.77, 95% confidence interval [CI]: 1.74-13.03) and history of a miscarriage (OR = 2.14, 95% CI: 1.02-4.49), and cardiovascular disease (CVD) risk factors including smoking (OR = 8.60, 95% CI: 3.25-22.75) were significantly associated with PCAD. When the model was adjusted for change in SEIFA-IRSAD scores (from CADOSA/NWAHS to SAPSC) and age, pregnancy-mediated pregnancy complications including preterm birth (OR = 4.40, 95% CI: 1.61-12.05) and history of a miscarriage (OR = 2.09, 95% CI: 1.00-4.35), and CVD risk factor smoking (OR = 8.75, 95% CI: 3.32-23.07) were significantly associated with PCAD. Conclusion: SES at the time of pregnancy and change in SES were not associated with PCAD risk.

Pregnancy Complications Are Associated with Premature Coronary Artery Disease: Linking Three Cohorts.

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case-control study design. Cases (n = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21-5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22-4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05-11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD.

Anxiety and Depression in Early Gestation and the Association with Subsequent Gestational Diabetes Mellitus in a Disadvantaged Population.

OBJECTIVES: Evaluate the association between poor mental health and risk of developing gestational diabetes mellitus (GDM) in a cohort of women from a socioeconomically disadvantaged community. METHODS: A total of 1363 nulliparous women with singleton pregnancies recruited to the Screening Tests to Predict Poor Outcomes of Pregnancy study in Adelaide, Australia. Women were assessed for mental health in the first trimester, including likelihood of depression, high functioning anxiety, perceived stress and risk of developing a mental health disorder. GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Socioeconomic status was measured using the New Zealand Socioeconomic Index (NZSEI). RESULTS: Complete mental health data was available for 1281 participants. There was no statistically significant difference in SEI, depression, risk of mental health issues, high functioning anxiety and perceived stress between women who developed GDM and those who did not. There was no difference in history of depression nor risk of developing a high mental health disorder in first trimester after adjusting for SEI, BMI in first trimester, smoking status in first trimester and maternal age between women with a GDM pregnancy and those who did not. CONCLUSIONS FOR PRACTICE: There was no difference in markers of poor mental health in early pregnancy between women who subsequently did or did not develop GDM. Cohort participants were socioeconomically disadvantaged, potentially contributing to the lack of apparent differences in depression observed between groups. Socioeconomically disadvantaged women should be targeted in pre-conception planning to reduce risk of GDM.

Risk Factors for Early-Onset Versus Late-Onset Coronary Heart Disease (CHD): Systematic Review and Meta-Analysis.

AIM: We aimed to systematically compare literature on prevalence of modifiable and non-modifiable risk factors for early compared to late-onset coronary heart disease (CHD). METHODS: PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol registered in PROSPERO CRD42020173216). Study quality was assessed using the National Heart, Lung and Blood Institute tool for observational and case-control studies. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences (MD)/standardised MD (SMD) with 95% confidence intervals (CI) for categorical and continuous variables. RESULTS: Individuals presenting with early-onset CHD (age <65 years) compared to late-onset CHD had higher mean body mass index (MD 1.07 kg/m2; 95% CI 0.31-1.83), total cholesterol (SMD 0.43; 95% CI 0.23-0.62), low-density lipoprotein (SMD 0.26; 95% CI 0.15-0.36) and triglycerides (SMD 0.50; 95% CI 0.22-0.68) with lower high-density lipoprotein-cholesterol (SMD 0.26; 95% CI -0.42--0.11). They were more likely to be smokers (OR 1.76, 95% CI 1.39-2.22) and have a positive family history of CHD (OR 2.08, 95% CI 1.74-2.48). They had lower mean systolic blood pressure (MD 4.07 mmHg; 95% CI -7.36--0.78) and were less likely to have hypertension (OR 0.47, 95% CI 0.39-0.57), diabetes mellitus (OR 0.56, 95% CI 0.51-0.61) or stroke (OR 0.31, 95% CI 0.24-0.42). CONCLUSION: A focus on weight management and smoking cessation and aggressive management of dyslipidaemia in young adults may reduce the risk of early-onset CHD.

Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccines among pregnant women (the EPIC study): study protocol.

BACKGROUND: Influenza and COVID-19 infections during pregnancy may have serious adverse consequences for women as well as their infants. However, uptake of influenza and COVID-19 vaccines during pregnancy remains suboptimal. This study aims to assess the effectiveness of a multi-component nudge intervention to improve influenza and COVID-19 vaccine uptake among pregnant women. METHODS: Pregnant women who receive antenatal care at five tertiary hospitals in South Australia, Western Australia and Victoria will be recruited to two separate randomised controlled trials (RCTs). Women will be eligible for the COVID-19 RCT is they have received two or less doses of a COVID-19 vaccine. Women will be eligible for the influenza RCT if they have not received the 2023 seasonal influenza vaccine. Vaccination status at all stages of the trial will be confirmed by the Australian Immunisation Register (AIR). Participants will be randomised (1:1) to standard care or intervention group (n = 1038 for each RCT). The nudge intervention in each RCT will comprise three SMS text message reminders with links to short educational videos from obstetricians, pregnant women and midwives and vaccine safety information. The primary outcome is at least one dose of a COVID-19 or influenza vaccine during pregnancy, as applicable. Logistic regression will compare the proportion vaccinated between groups. The effect of treatment will be described using odds ratio with a 95% CI. DISCUSSION: Behavioural nudges that facilitate individual choices within a complex context have been successfully used in other disciplines to stir preferred behaviour towards better health choices. If our text-based nudges prove to be successful in improving influenza and COVID-19 vaccine uptake among pregnant women, they can easily be implemented at a national level. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05613751. Registered on November 14, 2022.

The association of breast feeding for at least six months with hemodynamic and metabolic health of women and their children aged three years: an observational cohort study.

BACKGROUND: Breastfeeding is important for both mother and child in reducing risk of future cardiovascular disease. Therefore, it may be an effective method to improve cardio-metabolic health, particularly those who are exposed to pregnancy complications which increase later CVD risk for both mother and child. The aim of this study is to assess differences in cardiometabolic health at three years postpartum in mothers who breastfed for at least six months and their children compared to those who did not. METHODS: Women and children from the Screening Tests to Predict Poor Outcomes of Pregnancy (STOP) study (2015-2017) were invited to attend a health check-up at three years postpartum. Women's breastfeeding status at least six months postpartum was ascertained through their child health record. Anthropometric and hemodynamic measurements were taken from women and their children. A fasting blood sample was taken from women to measure blood glucose and lipids. RESULTS: A total of 160 woman-child dyads were assessed in this study. Women who breastfed for at least six months had significantly lower maternal BMI, systolic blood pressure, diastolic blood pressure, mean arterial pressure, central systolic blood pressure, and central diastolic blood pressure than those who did not and this did not change after adjusting for BMI and socioeconomic index in early pregnancy, prenatal smoking and maternal age in early pregnancy. Subgroup analysis on women who had one or more pregnancy complications during the index pregnancy (i.e. preeclampsia, gestational hypertension, delivery of a small for gestational age infant, delivery of a preterm infant, and/or gestational diabetes mellitus) demonstrated that women who breastfed for at least six months had significantly lower maternal systolic and diastolic blood pressures, serum insulin and triglycerides, and higher HDL cholesterol. There were no differences in child anthropometric or hemodynamic variables at three years of age between those children who had been breastfed for at least six months and those who had not. CONCLUSION: Breastfeeding for at least six months may reduce some maternal; cardiovascular risk factors in women at three years postpartum, in particular, in those who have experienced a complication of pregnancy. TRIAL REGISTRATION: ACTRN12614000985684 (12/09/2014).

4CMenB sustained vaccine effectiveness against invasive meningococcal B disease and gonorrhoea at three years post programme implementation.

OBJECTIVES: To evaluate persistence of vaccine effectiveness (VE) and vaccine impact (VI) on invasive meningococcal B (MenB) disease and gonorrhoea at three years after implementation of a state funded 4CMenB programme for infants, children, adolescents and young people in South Australia. METHODS: VI was assessed using a Poisson or negative binomial regression model, and VE was estimated using screening and case-control methods. Chlamydia controls were used to estimate VE in the primary analysis to control potential confounding effects such as high-risk sexual behaviour associated with sexually transmitted infections. RESULTS: During the three-year programme, reductions of 63.1% (95%CI 29.0-80.9%) and 78.5% (95%CI 33.0-93.1%) in incidence of MenB disease were observed in infants and adolescents, respectively. There were no cases in infants who had received three doses of 4CMenB. Two-dose VE against MenB disease was 90.7% (95%CI 6.9-99.1%) for the childhood programme and 83.5% (95%CI 0-98.2%) for the adolescent programme. Two-dose VE against gonorrhoea in adolescents was 33.2% (95%CI 15.9-47.0%). Lower VE estimates were demonstrated after 36 months post-vaccination (23.2% (95%CI 0-47.5%)> 36 months post-vaccination compared to 34.9% (95%CI 15.0-50.1%) within 6-36 months). Higher VE estimates were found after excluding patients with repeat gonorrhoea infections (37.3%, 95%CI 19.8-51.0%). For gonorrhoea cases co-infected with chlamydia VE was maintained (44.7% (95%CI 17.1-63.1%). CONCLUSION: The third-year evaluation results show persistent vaccine effectiveness of 4CMenB against MenB disease in infants and adolescents. As this is the first ongoing programme for adolescents, moderate vaccine protection against gonorrhoea with waning effectiveness three years post-vaccination was demonstrated in adolescents and young adults. The additional protection of 4CMenB vaccine against gonorrhoea, likely through cross-protection should be considered in cost-effectiveness analyses. A booster dose may need to be further evaluated and considered in adolescents due to waning protection against gonorrhoea demonstrated after 36 months post-vaccination.

Risk Factors for Premature Coronary Heart Disease in Women Compared to Men: Systematic Review and Meta-Analysis.

Background: We aimed to systematically examine literature on the prevalence of known modifiable and nonmodifiable risk factors for premature coronary heart disease (PCHD) in women compared with men. Materials and Methods: PubMed, CINAHL, Embase, and Web of Science databases were searched. Review protocol is registered in PROSPERO (CRD42020173216). Quality was assessed using the National Heart, Lung, and Blood Institute tool. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences/standardized mean differences (SMD) with 95% confidence intervals (CIs) for categorical and continuous variables. Results: In this PCHD cohort (age <65 years), the mean age of presentation in women was 3 years older than men. Women had higher total cholesterol (SMD 0.11; 95% CI 0.00 to 0.23) and higher high-density lipoprotein cholesterol (SMD 0.49; 95% CI 0.29 to 0.69). Women were more likely to have hypertension (OR 1.51, 95% CI 1.42 to 1.60), diabetes mellitus (OR 1.78, 95% CI 1.55 to 2.04), obesity (OR 1.33, 95% CI 1.24 to 1.42), metabolic syndrome (OR 3.73, 95% CI 1.60 to 8.69), stroke (OR 1.63, 95% CI 1.51 to 1.77), peripheral vascular disorder (OR 1.67, 95% CI 1.43 to 1.96), and depression (OR 2.29, 95% CI 1.96 to 2.67). Women were less likely to be smokers (OR 0.60, 95% CI 0.55 to 0.66), have reported alcohol intake (OR 0.36, 95% CI 0.33 to 0.40), and reported use of illicit drug (OR 0.32, 95% CI 0.16 to 0.62). Conclusions: Risk factor profile in PCHD has a clear sex difference that supports early, aggressive, holistic, but sex-specific, approach to prevention.

A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529).

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1-28.7%) and 23.4% (95%CI: 13.5-33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1-37.1%) at three months to 3.9% (95%CI: -24.8-32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8-58.3%) and 57.3% (95%CI: 54.0-60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8-48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5-69.7%) at three months, decreased to 49% (95%CI: 35.7-63.4%) within six months, and increased to 86% after the first or second booster dose.

Asymptomatic SARS-CoV-2 Infection by Age: A Global Systematic Review and Meta-analysis.

BACKGROUND: Asymptomatic SARS-CoV-2 infections have raised concerns for public health policies to manage epidemics. This systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons globally by year of age. METHODS: We searched PubMed, Embase, medRxiv and Google Scholar on September 10, 2020, and March 1, 2021. We included studies conducted during January to December 2020, before routine vaccination against COVID-19. Because we expected the relationship between the asymptomatic proportion and age to be nonlinear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age. RESULTS: A total of 38 studies were included in the meta-analysis. In total, 6556 of 14,850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14,850, 95% CI: 43.3%-45.0%). The predicted asymptomatic proportion peaked in children (36.2%, 95% CI: 26.0%-46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95% CI: 3.4%-12.7%). CONCLUSIONS: Given the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.

Early pregnancy cardio metabolic risk factors and the prevalence of metabolic syndrome 10 years after the first pregnancy.

BACKGROUND: We aimed to compare risk factors for CVD 10 years postpartum among women who had ≥ 1 compared to no cardio metabolic risk factor in early first pregnancy. METHODS: Women of the SCOPE (Screening fOr Pregnancy Endpoints) study from Adelaide, South Australia were invited to participate in a cardiovascular risk assessment 10 years after the delivery of the first child. Data from 141 women who completed all the assessments are included in the analyses. RESULT: Compared to women who did not have any cardio metabolic risk factor at 15 ± 1 weeks' gestation during the first pregnancy, those who had ≥ 1 risk factor were 5.5 times more likely to have metabolic syndrome 10 years postpartum (aOR = 5.5, 95% CI 1.8-17.3, p = 0.004). Women who had ≥ 1cardio metabolic risk factor during the first pregnancy were more likely to be obese (p = 0.001), have high total cholesterol levels (p <0.001) or have increased insulin resistance (p <0.001) 10 years later compared to women who had no risk factor during the first pregnancy. 63.5% of the women with no cardio metabolic risk factor compared to 39% of women who had ≥ 1 risk factor in first pregnancy, had neither a complicated first pregnancy nor was diagnosed with MetS 10 years postpartum (p = 0.023). CONCLUSION: Cardio metabolic risk factors at the booking visit in the first pregnancy may be useful in identifying young women at risk of future CVD.

Asymmetric dimethylarginine and gestational diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: Emerging evidence demonstrates that asymmetric dimethylarginine (ADMA) levels are elevated in patients with or at risk of cardiovascular disease (CVD). Since women with gestational diabetes mellitus (GDM) are at high risk of future CVD, we conducted a systematic review and meta-analysis to compare ADMA concentrations between women with and without GDM during pregnancy and postpartum. METHODS: PubMed, Google Scholar, EMBASE, and CINAHL databases were searched. The review protocol is registered in PROSPERO (CRD42021276796). Study selection, data extraction, and data analyses were performed in accordance with PRISMA guidelines. Random-effects model was used to quantify ADMA levels in the study groups. RESULTS: Eleven studies provided data on 1148 women. Mean plasma ADMA concentration was 0.04 µmol/L (95% confidence interval (CI) -0.06-0.15) higher in pregnant women with GDM than those without GDM, but no significant difference was observed. In contrast, our meta-analysis demonstrated a significant increase in postpartum mean ADMA concentration (Mean Difference (MD) 0.11 µmol/L; 95% CI 0.05-0.16) among women with previous GDM compared to women without previous GDM. CONCLUSION: Elevated ADMA levels in GDM may be a CVD risk factor, suggesting that ADMA may be a potential biomarker for early CVD risk prediction in women with GDM.

Gestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum.

INTRODUCTION: Gestational diabetes mellitus (GDM) is thought to be associated with cardio-metabolic risk factor development in women and their children during the early postpartum period and early childhood. We hypothesized that these women and their children would exhibit increased abnormal cardio-metabolic risk factors three years after pregnancy. METHODS: Women from the Screening Tests to Predict Poor Outcomes of Pregnancy study were invited to attend a follow-up with the child from their index pregnancy at 3 years postpartum. Women and children were assessed for anthropometric measures and haemodynamic function. Fasting blood samples were obtained from women to assess lipid and glucose status. RESULTS: A total of 281 woman-child dyads participated in the 3-year follow-up, with 40 women developing GDM during their index pregnancy. Fasting serum insulin was higher in women with GDM in index pregnancy compared to those with an uncomplicated pregnancy. However, this association was mediated by early pregnancy BMI and socioeconomic index (SEI). The rate of metabolic syndrome was higher in the GDM group than the uncomplicated pregnancy group. Maternal GDM was associated with elevated maternal fasting serum triglycerides at 3 years after adjustment for early pregnancy BMI and SEI. Children exposed to GDM in utero had higher waist circumference compared to children born after an uncomplicated pregnancy, but this is mediated the above covariates. CONCLUSION: Exposure to GDM is associated with elevated serum triglycerides in women at 3 years postpartum but other cardiometabolic outcomes in women and children appear to be mediated by early pregnancy BMI and SEI.

Pregnancy complications and cardiovascular disease risk perception: A qualitative study.

OBJECTIVES: We aimed to assess women's perceptions on the long-term risks for cardiovascular disease (CVD) after major pregnancy complications. METHODS: Women who experienced major pregnancy complications and those who experienced uncomplicated pregnancies were invited to participate in a qualitative study. Focus group discussions (FGDs) and self-administered questionnaires were used to explore: The knowledge of long-term sequelae after experiencing a major pregnancy complication; Importance of education on heart health; The practicality of referral to a clinic after pregnancy complications; Willingness for regular postpartum clinic visits after pregnancy complications. A thematic qualitative analysis was undertaken. RESULTS: 26 women participated in four FGDs. The majority of women did not know of the association between major pregnancy complications and CVD. The main views expressed were: Women who experience pregnancy complications should receive education on improving heart health; An appointment for the first CVD risk screening visit needs to be made prior to discharge from the delivery suite; Women will benefit by having the option to select between a hospital and a general-practitioner based model of follow up. CONCLUSIONS: These views are important in developing postpartum strategies to reduce CVD risk among women who experience pregnancy complications.

Effectiveness and impact of the 4CMenB vaccine against invasive serogroup B meningococcal disease and gonorrhoea in an infant, child, and adolescent programme: an observational cohort and case-control study.

BACKGROUND: A programme of vaccination with the four-component serogroup B meningococcal (4CMenB) vaccine was introduced in South Australia for infants and children aged 0-3 years on Oct 1, 2018, and for senior school students in school years 10 and 11 (aged 15-16 years) and young adults aged 17-20 years on Feb 1, 2019. We aimed to evaluate vaccine effectiveness and impact on serogroup B meningococcal disease and gonorrhoea 2 years after implementation of the programme. METHODS: We did a cohort and case-control study among those targeted by the South Australia 4CMenB vaccination programme. We obtained disease notification data from SA Health, Government of South Australia, and vaccine coverage data from the South Australian records of the Australian Immunisation Register. Vaccine effectiveness was estimated as the reduction in the odds of infection using the screening and case-control methods. Vaccine impact was estimated as incidence rate ratios (IRRs), obtained by comparing case numbers in each year following the start of the vaccination programme with cases in the equivalent age cohort during the pre-vaccination programme years. We used Poisson or negative binomial models, as appropriate, with adjustment for changes in the incidence of serogroup B meningococcal disease in age cohorts not eligible for vaccination through the state programme. FINDINGS: 4CMenB vaccine coverage 2 years after introduction of the childhood vaccination programme was 94·9% (33 357 of 35 144 eligible individuals) for one dose, 91·4% (26 443 of 28 922) for two doses, and 79·4% (15 440 of 19 436) for three doses in infants. The one-dose (77·1%, 16 422 of 21 305) and two-dose (69·0%, 14 704 of 21 305) coverage was highest in adolescents born in 2003 (approximately year 10 students). 2 years after implementation of the childhood vaccination programme, incidence of serogroup B meningococcal disease was significantly reduced compared with before programme implementation in infants aged 12 weeks to 11 months (adjusted IRR [aIRR] 0·40 [95% CI 0·23-0·69], p=0·0011), but not in those aged 1 year (0·79 [0·16-3·87], p=0·77), 2 years (0·75 [0·18-3·14], p=0·70), or 4 years (3·00 [0·47-18·79], p=0·24). aIRRs were not calculable in those aged 3 or 5 years because of no cases occurring after programme implementation. aIRR for serogroup B meningococcal disease was 0·27 (0·06-1·16, p=0·078) in adolescents aged 15-18 years 2 years after implementation of the adolescent and young adult programme, and 1·20 (0·70-2·06, p=0·51) in those aged 19-21 years in the first year. Two-dose vaccine effectiveness against serogroup B meningococcal disease was estimated to be 94·2% (95% CI 36·6-99·5) using the screening method and 94·7% (40·3-99·5) using the case-control method in children, and 100% in adolescents and young adults (no cases reported after implementation). Estimated two-dose vaccine effectiveness against gonorrhoea in adolescents and young adults was 32·7% (8·3-50·6) based on the case-control method using age-matched individuals with chlamydia infection as controls. INTERPRETATION: 4CMenB vaccine shows sustained effectiveness against serogroup B meningococcal disease 2 years after introduction in infants and adolescents, and moderate effectiveness against gonorrhoea in adolescents. The high vaccine effectiveness against serogroup B meningococcal disease is likely due to high coverage in the target age groups and close antigenic match between the 4CMenB vaccine and the disease-associated serogroup B meningococcal strains circulating in South Australia. COVID-19-related physical distancing policies might have contributed to further declines in serogroup B meningococcal disease cases during the programme's second year. FUNDING: SA Health, Government of South Australia.