Energy and nutrient intake by 11-13-year-old young adolescents attending private schools in Delhi, India.

There are no high-quality data on dietary behavior of adolescents in India. This study aimed to assess the intake of energy (E), macronutrients and selected micronutrients in a sample of 11-13-year-old schoolchildren in Delhi, India. Participants from private schools (n=10) recorded dietary intake using a 3-day food diary. Information was entered into the dietary assessment tool, Intake24, to ascertain portion size and convert data into nutrient intake through integrated food tables. Of the 514 consenting participants, 393 (76.4%) (169 girls, 224 boys) aged 11.4 (± 1.8) years completed the study. The median (interquartile range (IQR) daily E intake was 2580 (2139.3-2989.8) kcal [10.8 (9.0 -12.5) MJ] for girls, and 2941.5 (2466.7- 3599.3) kcal [12.3 (10.3- 15.2) MJ] for boys. The median (IQR) daily nutrient intakes for girls and boys respectively were: protein 64.6 (54.8-79.3) g, 74.4 (61.4; 89.4) g; carbohydrate 336.5 (285.3- 393.6) g, 379.6 (317.8-461.8) g; and saturated fat 45.6 (34.8-58.3) g, 54.6 (41.9-69.5) g. There were no significant between-gender differences in percent E from protein (10.2 (9.2 - 11.4)), or carbohydrate (52.4 (48.7- 56.7)). Girls obtained less percent E from saturated fat (16.1 (11.0-18.2) compared with boys 16.3 (14.2 - 19.1) (P<0.05). E from saturated fat was above Food and Agriculture Organization recommendations in >74% participants. The EAR for iron was achieved by < 40% of girls. In conclusion, strategies to optimize dietary intake of adolescents in India should focus on preventing excess intakes of E and saturated fat, and improving iron intake in girls.

Sources and determinants of free sugars intake by 5-year-old Australian children in the SMILE cohort.

Reducing free sugars intake is important for the prevention of dental caries and obesity in children. The study aimed to determine the amount and sources of free sugars known to contribute to dental caries, and identify sociodemographic determinants of intake by children aged 5 years in Australia. Cross-sectional analysis of dietary data from a cohort study, collected using a customized food frequency questionnaire were used to calculate free sugars intake as grams/day and percentage contribution to Estimated Energy Requirement (EER). The percent contribution of food sources to free sugars intake was derived. Sociodemographic determinants of achieving intakes within WHO thresholds (i.e., <5% and <10% Energy were explored with multinomial logistic regression. Complete data were available for 641 children (347 boys, 294 girls). Median (IQR) free sugars intake (g/day) was 31.6 (21.3-47.6) in boys and 28.1 (19.6-47.9) in girls. The median (IQR) percentage contribution to EER was 7.9 (5.4-12.7); 21% and 42% of children had intakes <5% EER and between 5% and <10%, respectively. The main sources of free sugars were: (1) Cakes, Biscuits and Cereal Bars; (2) Sweetened Milk Products (predominantly yoghurts) and (3) Desserts. Maternal university education, single-parent household, and maternal place of birth being Australia or New Zealand were associated with free sugars intake <5% EER. In conclusion, less than a quarter of 5-year-old children in the SMILE cohort achieved the WHO recommendations to limit free sugars to <5% EER. Strategies to lower free sugars intake could target priority populations such migrants, populations with lower levels of education or health literacy and identify areas for intervention in the wider food environments that children are exposed to.

Geographical distribution of invasive meningococcal disease and carriage: A spatial analysis.

Little information exists concerning the spatial relationship between invasive meningococcal disease (IMD) cases and Neisseria meningitidis (N. meningitidis) carriage. The aim of this study was to examine whether there is a relationship between IMD and asymptomatic oropharyngeal carriage of meningococci by spatial analysis to identify the distribution and patterns of cases and carriage in South Australia (SA). Carriage data geocoded to participants' residential addresses and meningococcal case notifications using Postal Area (POA) centroids were used to analyse spatial distribution by disease- and non-disease-associated genogroups, as well as overall from 2017 to 2020. The majority of IMD cases were genogroup B with the overall highest incidence of cases reported in infants, young children, and adolescents. We found no clear spatial association between N. meningitidis carriage and IMD cases. However, analyses using carriage and case genogroups showed differences in the spatial distribution between metropolitan and regional areas. Regional areas had a higher rate of IMD cases and carriage prevalence. While no clear relationship between cases and carriage was evident in the spatial analysis, the higher rates of both carriage and disease in regional areas highlight the need to maintain high vaccine coverage outside of the well-resourced metropolitan area.

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.

Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort.

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.

Intra-urban risk assessment of occupational injuries and illnesses associated with current and projected climate: Evidence from three largest Australian cities.

BACKGROUND: Increased risk of occupational injuries and illnesses (OI) is associated with ambient temperature. However, most studies have reported the average impacts within cities, states, or provinces at broader scales. METHODS: We assessed the intra-urban risk of OI associated with ambient temperature in three Australian cities at statistical area level 3 (SA3). We collected daily workers' compensation claims data and gridded meteorological data from July 1, 2005, to June 30, 2018. Heat index was used as the primary temperature metric. We performed a two-stage time series analysis: we generated location-specific estimates using Distributed Lag Non-Linear Models (DLNM) and estimated the cumulative effects with multivariate meta-analysis. The risk was estimated at moderate heat (90th percentile) and extreme heat (99th percentile). Subgroup analyses were conducted to identify vulnerable groups of workers. Further, the OI risk in the future was estimated for two projected periods: 2016-2045 and 2036-2065. RESULTS: The cumulative risk of OI was 3.4% in Greater Brisbane, 9.5% in Greater Melbourne, and 8.9% in Greater Sydney at extreme heat. The western inland regions in Greater Brisbane (17.4%) and Greater Sydney (32.3%) had higher risk of OI for younger workers, workers in outdoor and indoor industries, and workers reporting injury claims. The urbanized SA3 regions posed a higher risk (19.3%) for workers in Greater Melbourne. The regions were generally at high risk for young workers and illness-related claims. The projected risk of OI increased with time in climate change scenarios. CONCLUSIONS: This study provides a comprehensive spatial profile of OI risk associated with hot weather conditions across three cities in Australia. Risk assessment at the intra-urban level revealed strong spatial patterns in OI risk distribution due to heat exposure. These findings provide much-needed scientific evidence for work, health, and safety regulators, industries, unions, and workers to design and implement location-specific preventative measures.

A comparison of survival models for prediction of eight-year revision risk following total knee and hip arthroplasty.

BACKGROUND: There is increasing interest in the development and use of clinical prediction models, but a lack of evidence-supported guidance on the merits of different modelling approaches. This is especially true for time-to-event outcomes, where limited studies have compared the vast number of modelling approaches available. This study compares prediction accuracy and variable importance measures for four modelling approaches in prediction of time-to-revision surgery following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: The study included 321,945 TKA and 151,113 THA procedures performed between 1 January 2003 and 31 December 2017. Accuracy of the Cox model, Weibull parametric model, flexible parametric model, and random survival forest were compared, with patient age, sex, comorbidities, and prosthesis characteristics considered as predictors. Prediction accuracy was assessed using the Index of Prediction Accuracy (IPA), c-index, and smoothed calibration curves. Variable importance rankings from the Cox model and random survival forest were also compared. RESULTS: Overall, the Cox and flexible parametric survival models performed best for prediction of both TKA (integrated IPA 0.056 (95% CI [0.054, 0.057]) compared to 0.054 (95% CI [0.053, 0.056]) for the Weibull parametric model), and THA revision. (0.029 95% CI [0.027, 0.030] compared to 0.027 (95% CI [0.025, 0.028]) for the random survival forest). The c-index showed broadly similar discrimination between all modelling approaches. Models were generally well calibrated, but random survival forest underfitted the predicted risk of TKA revision compared to regression approaches. The most important predictors of revision were similar in the Cox model and random survival forest for TKA (age, opioid use, and patella resurfacing) and THA (femoral cement, depression, and opioid use). CONCLUSION: The Cox and flexible parametric models had superior overall performance, although all approaches performed similarly. Notably, this study showed no benefit of a tuned random survival forest over regression models in this setting.

The impact of non-pharmaceutical interventions on COVID-19 cases in South Australia and Victoria.

OBJECTIVE: To assess the impact of different non-pharmaceutical interventions (NPIs) on COVID-19 cases across Victoria and South Australia. METHODS: Poisson regression models were fit to examine the effect of NPIs on weekly COVID-19 case numbers. RESULTS: Mask-wearing in Victoria had a pronounced lag effect of two weeks with an incidence rate ratio (IRR) of 0.27 (95%CI 0.26-0.29). Similarly, the effect of border closure (IRR 0.18; 95%CI 0.14-0.22) in South Australia and lockdown (IRR 0.88; 95%CI 0.86-0.91) in Victoria showed a decrease in incidence two weeks after the introduction of these interventions. CONCLUSIONS: With the ongoing COVID-19 pandemic, varying levels of vaccination coverage rates and threats from variants of concern, NPIs are likely to remain in place. It is thus important to validate the effectiveness and timing of different interventions for disease control, as those that are more restrictive such as border control and lockdown can have an enormous impact on society. IMPLICATIONS FOR PUBLIC HEALTH: Low case numbers and deaths in Australia's first wave of COVID-19 are thought to be due to the timely use of interventions. The observed two-week lag effect associated with a decrease in incidence provides justification for early implementation of NPIs for COVID-19 management and future pandemics.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

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.

Effect of a multi-faceted rapid response system re-design on repeat calling of the rapid response team.

BACKGROUND: Repeat Rapid Response Team (RRT) calls are associated with increased in-hospital mortality risk and pose an organisation-level resource burden. Use of Non-Technical Skills (NTS) at calls has the potential to reduce potentially preventable repeat calling. NTS are usually improved through training, although this consumes time and financial resources. Re-designing the Rapid Response System (RRS) to promote use of NTS may provide a feasible alternative. METHODS: A pre-post observational study was undertaken to assess the effect of an RRS re-design that aimed to promote use of NTS during RRT calls. The primary outcome was the proportion of admissions each month subject to repeat RRT calling, and the average number of repeat calls per admission each month was the secondary outcome of interest. Univariate and multivariable interrupted time series analyses compared outcomes between the two study phases. RESULTS: The proportion of admissions with repeat calls each month increased across both phases of the study period, but the increase was lower in the post re-design phase (change in regression slope -0.12 (standard error 0.07) post versus pre re-design). The multivariable model predicted a 6% reduction (95% confidence interval -15.1-3.1; P = 0.19) in the proportion of admissions having repeat calls at the end of the post redesign phase study compared to the predicted proportion in the absence of the re-design. The average number of calls per admission was also predicted to decrease in the post re-design phase, with an estimated difference of -0.07 calls per admission (equivalent to one fewer repeat call per 14 patients who had RRT calls) at the end of the post re-design phase (95% confidence interval -0.23-0.08, P = 0.35). CONCLUSION: This study of an RRS re-design showed modest, but not statistically significant, reductions in the proportion of admissions with repeat calls and the mean number of repeat calls per admission. Given the economic and workforce capacity issues that all health care systems now face, even small improvements in the RRS may have lasting impact across the organisation. For the potential interest of RRS managers, this paper presents a pragmatic, low-cost initiative intended to enhance communication and cooperation at RRT calls.

An Observational Study to Assess the Effectiveness of 4CMenB against Meningococcal Disease and Carriage and Gonorrhea in Adolescents in the Northern Territory, Australia-Study Protocol.

Invasive meningococcal disease (IMD) causes significant morbidity and mortality worldwide with serogroup B being the predominant serogroup in Australia and other countries for the past few decades. The licensed 4CMenB vaccine is effective in preventing meningococcal B disease. Emerging evidence suggests that although 4CMenB impact on carriage is limited, it may be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. This study protocol describes an observational study that will assess the effect of the 4CMenB vaccine against meningococcal carriage, IMD and gonorrhoea among adolescents in the Northern Territory (NT). All 14-19-year-olds residing in the NT with no contraindication for 4CMenB vaccine will be eligible to participate in this cohort study. Following consent, two doses of 4CMenB vaccine will be administered two months apart. An oropharyngeal swab will be collected at baseline and 12 months to detect pharyngeal carriage of Neisseria meningitidis by PCR. The main methodological approaches to assess the effect of 4CMenB involve a nested case control analysis and screening method to assess vaccine effectiveness and an Interrupted Time Series regression analysis to assess vaccine impact. Research ethics approvals have been obtained from Menzies and Central Australian Human Research Ethics Committees and the Western Australian Aboriginal Health Ethics Committee. Results will be provided in culturally appropriate formats for NT remote and regional communities and published in international peer reviewed journals. ClinicalTrials.gov Identifier: NCT04398849.

Outdoor ambient temperatures and occupational injuries and illnesses: Are there risk differences in various regions within a city?

Increased risk of occupational injuries and illnesses (OI) is associated with hot ambient temperatures. However, the existing evidence of risk estimation is limited to large regions at the city or provincial scales. For effective and localized occupational health risk management, spatio-temporal analysis should be carried out at the intra-city level to identify high-risk areas within cities. This study examined the exposure-response relationship between ambient temperatures and OI at the intra-city scale in Greater Adelaide, Australia. Vulnerable groups of workers, in terms of workers' characteristics, the nature of their work, and workplace characteristics were identified. Further, the projected risk of OI was quantified in various climate change scenarios. The temperature-OI association was estimated using a time-series study design combined with Distributed Lag Non-linear Models. Daily workers' compensation claims (2005-2018) were merged with 5 km gridded meteorological data of maximum temperature (°C) at Statistical Area Level 3 in Greater Adelaide. Region-wise subgroup analyses were conducted to identify vulnerable groups of workers. Future projections (2006-2100) were conducted using downscaled climate projections and the risk was quantified using log-linear extrapolation. The analyses were performed in R 4.1.0. The overall OI risk was 16.7% (95%CI: 10.8-23.0) at moderate heat (90th percentile) and increased to 25.0% (95%CI: 16.4-34.2) at extreme heat (99th percentile). Northern Adelaide had a higher risk of OI for all types of workers at moderate heat, while western regions had a high risk for indoor industries. Southern and eastern regions had a higher OI risk for males, older workers, and outdoor industries at extreme heat. The projected risk of OI is estimated to increase from 20.8% (95%CI: -0.2-46.3) in 2010s to 22.9% (95%CI: -8.0-64.1) by 2050s. Spatio-temporal risk assessment at the intra-city scale can help us identify high-risk areas, where targeted interventions can be efficiently employed to reduce the socio-economic burden of OI.

Dispensing of clomiphene citrate to treat infertility: medication supplied and population prevalence of assisted pregnancies and multiple births.

OBJECTIVE: To determine the proportion of pregnancies resulting in birth that were conceived with the use of clomiphene citrate (CC) and the frequency of multiple pregnancy. DESIGN: Whole-of-population cohort study, constructed through data linkage. Comprehensive Australian Government records of dispensed medications were linked to state Perinatal Registry records for all births of at least 20 weeks' gestation. SETTING: The state of South Australia. PATIENT(S): Women who maintained pregnancy for at least 20 weeks and gave birth between July 2003 and December 2015, a total of 150,713 women with 241,561 pregnancies. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Ongoing pregnancy occurring in proximity to CC, defined as dispensing from 90 days before to the end of a conception window derived from newborn date of birth and gestational age. RESULT(S): Linkage to dispensed prescription records was achieved for 97.9% of women. Women who conceived with CC tended to be older and socioeconomically advantaged and more likely than other women to have a history of miscarriage. Ongoing pregnancies associated with CC comprised 1.6% of the total; 5.7% were multiple births (mostly twins, 94.6%) compared with 1.5% in the remainder (98.5% twins). CONCLUSION(S): In South Australia, 1.6% of pregnancies (1 in 60) of at least 20 weeks' gestation were conceived proximal to CC dispensing. Of these, 5.7% were multiple pregnancies. This takes the proportion of women who achieved an ongoing pregnancy with medical assistance from 4.4%, based on reports from assisted reproductive technology clinics, to 6% in total.

Body mass index and vaccine responses following influenza vaccination during pregnancy.

BACKGROUND AND AIMS: Influenza vaccination is recommended by the World Health Organisation for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza infection. Various factors can influence vaccine immunogenicity, with obesity being one factor implicated in varied responses. This study aimed to investigate the impact of body mass index (BMI) on vaccine responses following influenza vaccination during pregnancy. METHODS: Pregnant women attending the Women's and Children's Hospital in South Australia during 2014-2016 were invited to participate. Participant's clinical and demographic factors were recorded prior to administration of licensed seasonal influenza vaccination. Blood samples were collected before and one month post-vaccination to measure antibody responses by haemagglutination inhibition (HI) assay. Seroprotection was defined as a post-vaccination HI titre ≥ 1:40. Regression models assessed associations with failure to achieve seroprotective antibodies to H1, H3, and B influenza strains. RESULTS: A total of 96 women were enrolled in the study at a median gestation of 22 weeks with a BMI range of 18-49 kg/m2. Paired sera samples were available for 90/96 (94%). Most pregnant women (72/90, 80%) demonstrated seroprotective antibody titres to all three influenza vaccine antigens (A(H1N1)pdm09, A(H3N2), B/Yamagata) following vaccination. Compared with women with BMI < 30 kg/m2, those with high BMI were less likely to fail to achieve seroprotective antibodies, however this was not statistically significant (RR 0.42, 95% CI 0.11-1.68; p = 0.22). A greater proportion of women vaccinated during their second (47/53, 93%) or third trimester (18/25, 72%) demonstrated seroprotection to all three vaccine antigens following vaccination compared with women vaccinated during their first trimester (7/12, 58%). CONCLUSION: High BMI did not impair seroprotection levels following influenza vaccination in pregnant women. Gestation at vaccination may be an important consideration for optimising vaccine protection for pregnant women and their newborns. Further assessment of first trimester influenza vaccine responses is warranted.

Lessons for and from the COVID-19 pandemic response - An appraisal of guidance for the public health management of Invasive Meningococcal Disease.

BACKGROUND: COVID-19 has focussed public attention on the management of communicable disease like never before. Surveillance, contact tracing, and case management are recognised as key components of outbreak prevention. Development of guidance for COVID-19 has drawn from existing management of other communicable diseases, including Invasive Meningococcal Disease (IMD). IMD is a rare but severe outcome of Neisseria meningitidis infection that can be prevented through vaccination. Cases still occur sporadically, requiring ongoing surveillance and consistent management. To this end, national and international public health agencies have developed and published guidance for identification and management of IMD cases. AIM: To assess national and international guidelines for the public health management of IMD, with a focus on the recommendations for identification and management of "close contacts" to IMD cases. METHODS: Guidelines from six national and international public health agencies were assessed using a modified version of the Appraisal of Guidelines, Research and Evaluation (AGREE II) Instrument in four key domains: stakeholder involvement, developmental rigour, clarity, and applicability. A direct comparison of terminology and recommendations for identification and management of close contacts to IMD cases was also conducted. RESULTS: Guidelines from Europe and the United Kingdom rated most highly using the AGREE II Instrument, both presenting a clear, critical assessment of the strength of the available evidence, and the risks, costs, and benefits behind recommendations for management of close contacts. Direct comparison of guidelines identified inconsistencies in the language defining close contacts to IMD cases. CONCLUSION: Discrepancies between guidelines could be due to limited evidence concerning mechanisms behind disease transmission, along with the lack of a consistent process for development and review of guideline recommendations. COVID-19 management has demonstrated that international collaboration for development of public health guidance is possible, a practice that should be extended to management of other communicable diseases.

Extreme heat and occupational injuries in different climate zones: A systematic review and meta-analysis of epidemiological evidence.

BACKGROUND: The link between heat exposure and adverse health outcomes in workers is well documented and a growing body of epidemiological evidence from various countries suggests that extreme heat may also contribute to increased risk of occupational injuries (OI). Previously, there have been no comparative reviews assessing the risk of OI due to extreme heat within a wide range of global climate zones. The present review therefore aims to summarise the existing epidemiological evidence on the impact of extreme heat (hot temperatures and heatwaves (HW)) on OI in different climate zones and to assess the individual risk factors associated with workers and workplace that contribute to heat-associated OI risks. METHODS: A systematic review of published peer-reviewed articles that assessed the effects of extreme heat on OI among non-military workers was undertaken using three databases (PubMed, Embase and Scopus) without temporal or geographical limits from database inception until July 2020. Extreme heat exposure was assessed in terms of hot temperatures and HW periods. For hot temperatures, the effect estimates were converted to relative risks (RR) associated with 1 °C increase in temperature above reference values, while for HW, effect estimates were RR comparing heatwave with non-heatwave periods. The patterns of heat associated OI risk were investigated in different climate zones (according to Köppen Geiger classification) based on the study locations and were estimated using random-effects meta-analysis models. Subgroup analyses according to workers' characteristics (e.g. gender, age group, experience), nature of work (e.g. physical demands, location of work i.e. indoor/outdoor) and workplace characteristics (e.g. industries, business size) were also conducted. RESULTS: A total of 24 studies published between 2005 and 2020 were included in the review. Among these, 22 studies met the eligibility criteria, representing almost 22 million OI across six countries (Australia, Canada, China, Italy, Spain, and USA) and were included in the meta-analysis. The pooled results suggested that the overall risk of OI increased by 1% (RR 1.010, 95% CI: 1.009-1.011) for 1 °C increase in temperature above reference values and 17.4% (RR 1.174, 95% CI: 1.057-1.291) during HW. Among different climate zones, the highest risk of OI during hot temperatures was identified in Humid Subtropical Climates (RR 1.017, 95% CI: 1.014-1.020) followed by Oceanic (RR 1.010, 95% CI: 1.008-1.012) and Hot Mediterranean Climates (RR 1.009, 95% CI: 1.008-1.011). Similarly, Oceanic (RR 1.218, 95% CI: 1.093-1.343) and Humid Subtropical Climates (RR 1.213, 95% CI: 0.995-1.431) had the highest risk of OI during HW periods. No studies assessing the risk of OI in Tropical regions were found. The effects of hot temperatures on the risk of OI were acute with a lag effect of 1-2 days in all climate zones. Young workers (age < 35 years), male workers and workers in agriculture, forestry or fishing, construction and manufacturing industries were at high risk of OI during hot temperatures. Further young workers (age < 35 years), male workers and those working in electricity, gas and water and manufacturing industries were found to be at high risk of OI during HW. CONCLUSIONS: This review strengthens the evidence on the risk of heat-associated OI in different climate zones. The risk of OI associated with extreme heat is not evenly distributed and is dependent on underlying climatic conditions, workers' attributes, the nature of work and workplace characteristics. The differences in the risk of OI across different climate zones and worker subgroups warrant further investigation along with the development of climate and work-specific intervention strategies.

Evaluating the effectiveness of the 4CMenB vaccine against invasive meningococcal disease and gonorrhoea in an infant, child and adolescent program: protocol.

Invasive meningococcal disease causes significant morbidity and mortality worldwide, with serogroup B being one of the predominant serogroups in Australia for many years. The South Australian (SA) State Government recently funded the introduction of a 4CMenB vaccination program for infants, children and adolescents. In addition to protecting against invasive meningococcal disease, emerging evidence suggests the 4CMenB vaccine may also be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. The proposed project aims to evaluate the effectiveness of the SA 4CMenB vaccination program against invasive meningococcal disease and gonorrhoea through a combination of observational studies using routine surveillance and research data. The main methodological approaches involve an interrupted time series regression model, screening, and case-control analyses with different sets of controls to estimate vaccine impact and effectiveness. These analyses are designed to minimize potential biases inherent in all observational studies and to provide critical data on the effectiveness of the 4CMenB vaccine against two diseases of major global public health concern.

Safety of maternal pertussis vaccination on pregnancy and birth outcomes: A prospective cohort study.

OBJECTIVE: To evaluate the safety of maternal pertussis vaccination on pregnancy and birth outcomes. METHODS: The study population comprised 1272 healthy nulliparous pregnant women who participated in Screening Tests to identify poor Outcomes in Pregnancy (STOP) study at two obstetric hospitals in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination (confirmed by medical records), extensive amounts of pregnancy and birth outcome data collected by research midwives. Adjusted relative risks (aRRs) and hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and the temporal nature of each outcome. RESULTS: Of the 1272 women included in this study, 80.1% (n = 1019) received maternal pertussis vaccination. Vaccinated women had an average 0.22 weeks (95% CI 0.001, 0.44) longer gestation at delivery compared to unvaccinated women. Maternal pertussis vaccination was not associated with chorioamnionitis (aRR 0.71, 95% CI 0.27,1.82), gestational hypertension (aHR 1.24, 95% CI, 0.66, 2.30), preeclampsia (aHR 0.75, 95% CI 0.47, 1.18) nor preterm birth (aHR 0.99, 95% CI 0.47, 2.07). Neither risk of low birth weight (aHR 0.72, 95% CI 0.41, 1.27) nor small for gestational age infants (aHR 0.67,95% CI 0.29, 1.55) were increased following maternal pertussis vaccination. No associations between pertussis vaccination during pregnancy and adverse birth outcomes including admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for maternal influenza vaccination. CONCLUSION: Our study provides reassuring evidence of the safety of maternal pertussis vaccination with no increased risk of adverse pregnancy and birth outcomes. These findings support recommendations for pertussis vaccination during pregnancy to prevent morbidity and mortality associated with early-infant pertussis disease.

What Is the Effect of Using a Competing-risks Estimator when Predicting Survivorship After Joint Arthroplasty: A Comparison of Approaches to Survivorship Estimation in a Large Registry.

BACKGROUND: There is increasing interest in the development of statistical models that can be used to estimate risk of adverse patient outcomes after joint arthroplasty. Competing risk approaches have been recommended to estimate risk of longer-term revision, which is often likely to be precluded by the competing risk of death. However, a common approach is to ignore the competing risk by treating death as a censoring event and using standard survival models such as Cox regression. It is well-known that this approach can overestimate the event risk for population-level estimates, but the impact on the estimation of a patient's individualized risk after joint arthroplasty has not been explored. QUESTIONS/PURPOSES: We performed this study to (1) determine whether using a competing risk or noncompeting risk method affects the accuracy of predictive models for joint arthroplasty revision and (2) determine the magnitude of difference that using a competing risks versus noncompeting risks approach will make to predicted risks for individual patients. METHODS: The predictive performance of a standard Cox model, with competing risks treated as censoring events, was compared with the performance of two competing risks approaches, the cause-specific Cox model and Fine-Gray model. Models were trained and tested using data pertaining to 531,304 TKAs and 274,618 THAs recorded in the Australian Orthopaedic Association National Joint Replacement Registry between January 1, 2003 and December 31, 2017. The registry is a large database with near-complete capture and follow-up of all hip and knee joint arthroplasty in Australia from 2003 onwards, making it an ideal setting for this study. The performance of the three modeling approaches was compared in two different prediction settings: prediction of the 10-year risk of all-cause revision after TKA and prediction of revision for periprosthetic fracture after THA. The calibration and discrimination of each approach were compared using the concordance index, integrated Brier scores, and calibration plots. Calibration of 10-year risk estimates was further assessed within subgroups of age by comparing the observed and predicted proportion of events. Estimated 10-year risks from each model were also compared in three hypothetical patients with different risk profiles to determine whether differences in population-level performance metrics would translate into a meaningful difference for individual patient predictions. RESULTS: The standard Cox and two competing risks models showed near-identical ability to distinguish between high-risk and low-risk patients (c-index 0.64 [95% CI, 0.64 to 0.64] for all three modeling approaches for TKAs and 0.66 [95% CI 0.66 to 0.66] for THA). All models performed similarly in patients younger than 75 years, but for patients aged 75 years and older, the standard Cox model overestimated the risk of revision more than the cause-specific Cox and Fine-Gray model did. These results were echoed when predictions were made for hypothetical individual patients. For patients with a low competing risk of mortality, the 10-year predicted risks from the standard Cox, cause-specific Cox, and Fine-Gray models were similar for TKAs and THAs. However, a larger difference was observed for hypothetical 89-year-old patients with increased mortality risk. In TKAs, the revision risk for an 89-year-old patient was so low that this difference was negligible (0.83% from the cause-specific Cox model versus 1.1% from the standard Cox model). However, for THAs, where older age is a risk factor for both death and revision for periprosthetic fracture, a larger difference was observed in the 10-year predicted risks for a hypothetical 89-year-old patient (3.4% from the cause-specific Cox model versus 5.2% from the standard Cox model). CONCLUSION: When developing models to predict longer-term revision of joint arthroplasty, failing to use a competing risks modeling approach will result in overestimating the revision risk for patients with a high risk of mortality during the surveillance period. However, even in an extreme instance, where both the frequency of the event of interest and the competing risk of death are high, the largest absolute difference in predicted 10-year risk for an individual patient was just 1.8%, which may not be of consequence to an individual. Despite these findings, when developing or using risk prediction models, researchers and clinicians should be aware of how competing risks were handled in the modeling process, particularly if the model is intended for use populations where the mortality risk is high. LEVEL OF EVIDENCE: Level III, therapeutic study.