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Introduction: The purpose of this study was to describe the distribution of hospital and aged care services for older people, with a particular focus on transition care places, across Australia and to determine the relationships between the provision of these services. Methods: Aggregation of health and aged care service indicators by Aged Care Assessment Team (ACAT) region including: public and private acute and subacute (rehabilitation and geriatric evaluation and management) hospital beds, flexible and mainstream aged care places as at 30 June 2006. Results: There was marked variation in the distribution of acute and subacute hospital beds among the 79 ACAT regions. Aged care places were more evenly distributed. However, the distribution of transition care places was uneven. Rural areas had poorer provision of all beds. There was no evidence of coordination in the allocation of hospital and aged care services between the Commonwealth and state/territory governments. There was a weak relationship between the allocation of transition care places and the distribution of health and aged care services. Discussion: Overall, the distribution of services available to older persons is uneven across Australia. While the Transition Care Program is flexible and is providing rural communities with access to rehabilitation, it will not be adequate to address the increasing needs associated with the ageing of the Australian population. An integrated national plan for aged care and rehabilitation services should be considered. [ABSTRACT FROM AUTHOR]

This paper investigates the motives for (Study 1) and barriers to (Study 2) participation in physical activity by older Asian Indian immigrants to the United States. In Study 1, 100 older Asian Indians living in the United States completed the Participation Motivation Questionnaire for Older Adults. The most highly reported motives for participation were based around medical reasons and keeping healthy and active. Analyses of variance showed significant differences in reasons for participation in physical activity based on gender and age. In Study 2, 10 sedentary older Asian Indians living in the United States participated in focus group discussions. They viewed physical activity as being an integral part of everyday activity. Barriers identified included existing health problems, risk of injury, and issues associated with their new lifestyles in the United States. These culture-specific findings should be considered when developing interventions to encourage physical activity. [ABSTRACT FROM AUTHOR]

Objective: To develop a clinically relevant criterion for assessment of grip strength in older adults.Design: Longitudinal cohort study.Subjects: 1251 persons aged >/= 70 years who had grip strength measured as part of the Australian Longitudinal Study of Ageing (1992) and survived to a second interview 12 months later.Setting: Randomly selected sample of community-dwelling older adults residing in the Adelaide (South Australia) Statistical Division as defined by the Australian Bureau of Statistics.Main outcome measures: Participants were asked if they had any falls in the previous 12 months and the same question was repeated in the second interview.Statistical analyses: Logistic regression analyses were performed with faller status at 12 months as the dependent variable, grip strength >/= 25th percentile as the reference category and controlling for age, gender, faller status, BMI, exercise status and chronic disease.Results: For both genders the percentage falters was highest for those with grip strength < 25th percentile (< 28kg males, < 15.5kg females). After controlling for potential confounders, grip strength < 25th percentile independently predicted falls 12 months later (OR = 1.41, 95% CI=1.03-1.94, P = 0.034).Conclusion: In previous studies grip strength has been shown to be positively correlated with measures of nutritional health and in this study we have shown that it is an important determinant of future falls. This knowledge could be used to help prevent falls in the elderly in the future. Further research is warranted to determine whether nutritional support interventions can (1) improve or maintain grip strength among older adults and (2) aid in the prevention of subsequent accidental falls. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was conducted to identify risk factors for depressive symptomatology among older Chinese migrants. METHOD: One hundred and sixty-two Chinese migrants aged 55 years or older, living in the community and recruited via Chinese community organizations and general practitioners, were interviewed using a Chinese version of the Geriatric Depression Scale and measures of stressful life events, morbid conditions, self-rated health, acculturation, social support and service utilization. RESULT: Twenty-six percent of participants met the criteria for depressive symptomatology. No recent migrants showed symptoms of depression. Multiple logistic regression analysis showed that lower emotional support, greater number of visits to a doctor, difficulties in accessing health services and low New Zealand cultural orientation increased the risk of showing symptoms of depression. CONCLUSION: Significant numbers of older Chinese migrants appear to be depressed or at risk for depression and, while participants with depressive symptoms consulted general practitioners more than their counterparts without such symptoms, they reported greater difficulty in accessing health services. The findings point to the need for further epidemiological study of this growing sector of the population and investigation of the nature of its engagement with health services. Social support and aspects of acculturation may play a significant role in preventing depression. This also requires further investigation. [ABSTRACT FROM AUTHOR]

Negative attitudes towards aging can be a substantial obstacle to the delivery of quality health care to older adults. This study compared the attitudes towards older people and knowledge of aging held by clinical educators and students in physiotherapy and occupational therapy. Participants (n=175) completed a questionnaire that consisted of the Kogan scale concerning attitudes towards older people, Palmore's Facts of Aging Quiz version 1, and questions concerning social interaction with older people and demographic information. The clinical educators of both professional groups had significantly higher attitudinal scores than the student participants in this study. After controlling for the effect of age, clinical educators had a significantly lower negative bias on the Facts of Aging Quiz than the students. Significantly higher positive bias scores on the FAQI were reported by the occupational therapy students and clinical educators in comparison to their physiotherapy counterparts. A stronger curriculum emphasis throughout the academic programme together with increased clinical placements in settings providing care for older people may be necessary to better equip students for the workplace. [ABSTRACT FROM AUTHOR]

Aims: To assess the overall nutritional status of older adults participating in ambulatory rehabilitation and determine its association with relevant outcomes including physical function and quality of life. Design: Cross-sectional. Setting: Ambulatory rehabilitation service in the Southern region of Adelaide, Australia. Subjects: A total of 229 participants recruited as part of a RCT between June 2005 and June 2006, stroke (n=83), elective orthopedic procedure (n=44) and other medical condition (n=102). Methods: Nutritional status was measured using Mini Nutritional Assessment (MNA), Simplified Nutrition Appetite Questionnaire (SNAQ) and Body Mass Index. Functional performance was assessed using the Modified Barthel Index (MBI) and quality of life was measured using the Short Form-36 (SF-36). Results: Sixty-three percent of participants were malnourished or at risk of malnutrition according to the MNA and a third had a risk of >or= 5% weight loss in the subsequent six months, according to the SNAQ. Participants with a diagnosis other than stroke or elective orthopedic procedure were the most vulnerable, with 53% (n=74/140) classified as at risk of malnutrition or malnourished and a longer length of stay in hospital. Functional performance was no different for participants assessed as at risk of malnutrition or malnourished compared to the well nourished, but the SF-36 mental component score was significantly higher for those who were well nourished (p=0.003). Conclusion: Findings emphasise the magnitude of the malnutrition problem in ambulatory rehabilitation settings. Further research is required to evaluate the resource implications against expected benefits of providing nutrition interventions at this point. [ABSTRACT FROM AUTHOR]

Objective: Primary prevention strategies are critical to reduce the global burden of congenital heart defects (CHDs); this requires robust knowledge of causal agents. We aimed to review associations between CHDs and maternal advanced age, obesity, diabetes, hypertension, smoking and alcohol consumption and assess the causal nature of the associations., Design: Systematic review of reviews with application of a Bradford Hill criteria score-based causal assessment system., Data Sources: We searched PubMed, Embase and Episteminokos (January 1990-April 2023)., Eligibility Criteria: Systematic reviews of original epidemiological studies reporting association (relative risk) between one or more of the above maternal factors and CHDs overall (any type) in subsequent offspring., Data Extraction and Synthesis: Two independent reviewers selected eligible reviews, assessed the risk of bias and assigned the strength of evidence for causality., Results: There was strong evidence of a causal relationship between CHDs and maternal obesity (prepregnancy and early pregnancy) and pre-existing diabetes (six of seven Bradford Hill criteria met). For pre-existing hypertension (strength and biological gradient not met), and advanced age (strength, consistency and biological gradient not met), causal evidence was moderate. Evidence for the causal contribution of gestational diabetes, gestational hypertension, smoking and alcohol consumption was weak (strength, consistency, temporality and biological gradient not met)., Conclusions: CHDs can be reduced with stronger action to reduce maternal obesity and pre-existing diabetes prevalence. Investigating environmental exposures that have received limited attention, such as air pollutants and chemical exposures, is important to further inform prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infectious disease outbreaks are an ongoing public health concern, requiring extensive resources to prevent and manage. Invasive Meningococcal Disease (IMD) is a severe outcome of infection with Neisseria meningitidis bacteria, which can be carried and transmitted asymptomatically. IMD is not completely vaccine-preventable, presenting an ongoing risk of outbreak development. This review provides a retrospective assessment of public health management of IMD outbreaks., Methods: A systematic search was performed in PubMed and EMBASE. English-language studies reporting on IMD outbreaks and associated public health response were considered eligible. Reporting on key characteristics including outbreak size, duration, location, and public health response were assessed against Strengthening the Reporting of Observational studies in Epidemiology guidelines. A summary of lessons learned and author recommendations for each article were also discussed., Results: 39 eligible studies were identified, describing 35 outbreaks in seven regions. Responses to outbreaks were mostly reactive, involving whole communities over prioritising those at highest risk of transmission. Recent responses identified a need for more proactive and targeted controls. Reporting was inconsistent, with key characteristics such as outbreak size, duration, or response absent or incompletely described., Conclusion: There is a need for clear, comprehensive reporting on IMD outbreaks and their public health response to inform policy and practice for subsequent outbreaks of IMD and other infectious diseases., (© 2024. The Author(s).)

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s).)

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.

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/m 2 . 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/m 2 , 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., Competing Interests: Declaration of Competing Interest M Clarke, HS Marshall and S Evans are Investigators on clinical vaccine trials sponsored by Industry. Their institution (Women’s and Children’s Hospital) receives funding for Investigator led research and/or sponsored vaccine trials from Industry, including GSK, Pfizer, Sanofi, Novavax and Merck.  None of the authors receive any personal payments from Industry. S Lambert, LC Giles, SG Sullivan and LM Goodchild have no conflicts to declare. IG Barr has shares in an influenza vaccine producing company.  The WHO Collaborating Centre for Reference and Research on Influenza receives funds from Seqirus Limited and from the IFPMA for its influenza surveillance activities.  The WHO Collaborating Centre for Reference and Research on Influenza is funded by the Australian Government Department of Health.  The funding bodies were not involved in the collection, analysis or interpretation of data, the writing of the article, or the decision to submit the article for publication., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Each author certifies that neither he nor she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Our study aimed to assess the safety and protective effect of maternal influenza vaccination on pregnancy and birth outcomes., Methods: The study population comprised 1253 healthy nulliparous pregnant women in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination status (confirmed by medical records), pregnancy, and birth outcome data collected by midwives. Adjusted relative risks (aRRs) and adjusted hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and temporal nature of each outcome., Findings: Maternal influenza vaccination (48%, 603 of 1253) reduced the risk for pre-delivery hospitalisation with influenza like illness (aHR 0•61; 95% CI 0•39, 0•97). Maternal influenza vaccination was not associated with spontaneous abortion (aHR 0•42, 95% CI 0•12, 1•45), chorioamnionitis (aRR 0•78, 95% CI, 0•32, 1•88), gestational hypertension (aHR 0•78, 95% CI 0•47, 1•29), pre-eclampsia (aHR 0.84, 95% CI 0•54, 1•27), gestational diabetes (aHR 1•16, 95% CI 0•82, 1•66) nor preterm birth (aHR 0•94, 95% CI 0•59, 1•49). No associations between antenatal influenza vaccination and congenital anomalies, admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for pertussis vaccination. We observed a protective effect of maternal influenza vaccination on low birth weight (aHR 0•46, 95% CI 0•23, 0•94) and a marginal protective effect on small for gestational age births (aHR 0•65, 95% CI 0•40, 1•04) during periods of high influenza activity., Interpretation: These results support the safety of maternal influenza vaccination and suggest a protective effect in reducing the rates of low birthweight and small for gestational age births., Funding: There was no funding for this study., Competing Interests: HSM has been an investigator on clinical trials funded by pharmaceutical companies including Pfizer, GSK Sanofi-Pasteur, Novartis. Her institution receives funding for Investigator led research. HSM receives no personal payments from Industry. The remaining authors have no conflicts of interest to declare., (© 2020 The Author(s).)

Backgrounds: We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at-risk children with a first-degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study., Methods: Fecal elastase-1 (FE-1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty-eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody-negative children (non-progressors) followed similarly were age and gender-matched with the progressors. An adjusted linear mixed model compared FE-1 concentrations in progressors and non-progressors., Results: Baseline FE-1 did not differ between progressors and non-progressors, or by HLA DR type or proband status. FE-1 decreased over time in progressors in comparison to non-progressors (Wald statistic 5.46, P = .02); in some progressors the fall in FE-1 preceded the onset of IA., Conclusions: Pancreatic exocrine function decreases in the majority of young at-risk children who progress to IA and T1D., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Microbial exposures in utero and early life shape the infant microbiome, which can profoundly impact on health. Compared to the bacterial microbiome, very little is known about the virome. We set out to characterize longitudinal changes in the gut virome of healthy infants born to mothers with or without type 1 diabetes using comprehensive virome capture sequencing., Methods: Healthy infants were selected from Environmental Determinants of Islet Autoimmunity (ENDIA), a prospective cohort of Australian children with a first-degree relative with type 1 diabetes, followed from pregnancy. Fecal specimens were collected three-monthly in the first year of life., Results: Among 25 infants (44% born to mothers with type 1 diabetes) at least one virus was detected in 65% (65/100) of samples and 96% (24/25) of infants during the first year of life. In total, 26 genera of viruses were identified and >150 viruses were differentially abundant between the gut of infants with a mother with type 1 diabetes vs without. Positivity for any virus was associated with maternal type 1 diabetes and older infant age. Enterovirus was associated with older infant age and maternal smoking., Conclusions: We demonstrate a distinct gut virome profile in infants of mothers with type 1 diabetes, which may influence health outcomes later in life. Higher prevalence and greater number of viruses observed compared to previous studies suggests significant underrepresentation in existing virome datasets, arising most likely from less sensitive techniques used in data acquisition., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Individual susceptibility to allergic diseases is developmentally programmed by early-life exposures. Evidence from preclinical studies suggests that intrauterine growth restriction is protective against later inflammatory responses to allergens., Objective: We sought to evaluate whether prenatal growth affects susceptibility to allergy in human subjects., Methods: We systematically searched for relevant studies in 11 databases, including Web of Science, ProQuest, EMBASE, and PubMed. We included only studies that corrected for gestational age or were restricted to full-term infants to separate effects of fetal growth from those of prematurity., Results: The 42 eligible studies included prospective and retrospective cohort, cross-sectional, and case-control studies. Only 2 studies reported allergic asthma. A birth weight increase of 1 kg was associated with a 44% greater risk of food allergy in children (odds ratio [OR], 1.44; 95% CI, 1.04-1.99; P = .001), a 17% greater risk of ever allergic dermatitis in children (OR, 1.17; 95% CI, 1.04-1.32; P = .008), and a 34% greater risk of ever or current allergic dermatitis in infants up to 2 years of age (OR, 1.34; 95% CI, 1.08-1.68; P = .009). Risks of allergic rhinitis were not associated with birth weight., Conclusions: The results of these meta-analyses suggest that intrauterine growth restriction protects against allergic diseases in human subjects consistent with preclinical evidence but that effects might differ between allergic diseases. The strongest evidence is available for infancy and early childhood, and additional studies in older children and adults are needed to determine whether the effects of prenatal growth on each allergic disease persist or differ between those with severe and mild phenotypes., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aims/hypothesis: To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls., Methods: We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up., Results: Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008)., Conclusions/interpretation: Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The importance of gut bacteria in human physiology, immune regulation, and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome are largely unknown; particularly lacking are studies in pregnancy. We used comprehensive virome capture sequencing to characterize the gut virome of pregnant women with and without type 1 diabetes (T1D), longitudinally followed in the Environmental Determinants of Islet Autoimmunity study., Methods: In total, 61 pregnant women (35 with T1D and 26 without) from Australia were examined. Nucleic acid was extracted from serial fecal specimens obtained at prenatal visits, and viral genomes were sequenced by virome capture enrichment. The frequency, richness, and abundance of viruses were compared between women with and without T1D., Results: Two viruses were more prevalent in pregnant women with T1D: picobirnaviruses (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.0-17.1; P = .046) and tobamoviruses (OR, 3.2; 95% CI, 1.1-9.3; P = .037). The abundance of 77 viruses significantly differed between the 2 maternal groups (≥2-fold difference; P < .02), including 8 Enterovirus B types present at a higher abundance in women with T1D., Conclusions: These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct profile of viruses in women with T1D.

Aims/hypothesis: Beta cell function in type 1 diabetes is commonly assessed as the average plasma C-peptide concentration over 2 h following a mixed-meal test (CP AVE ). Monitoring of disease progression and response to disease-modifying therapy would benefit from a simpler, more convenient and less costly measure. Therefore, we determined whether CP AVE could be reliably estimated from routine clinical variables., Methods: Clinical and fasting biochemical data from eight randomised therapy trials involving participants with recently diagnosed type 1 diabetes were used to develop and validate linear models to estimate CP AVE and to test their accuracy in estimating loss of beta cell function and response to immune therapy., Results: A model based on disease duration, BMI, insulin dose, HbA 1c , fasting plasma C-peptide and fasting plasma glucose most accurately estimated loss of beta cell function (area under the receiver operating characteristic curve [AUROC] 0.89 [95% CI 0.87, 0.92]) and was superior to the commonly used insulin-dose-adjusted HbA 1c (IDAA1c) measure (AUROC 0.72 [95% CI 0.68, 0.76]). Model-estimated CP AVE (CP EST ) reliably identified treatment effects in randomised trials. CP EST , compared with CP AVE , required only a modest (up to 17%) increase in sample size for equivalent statistical power., Conclusions/interpretation: CP EST , approximated from six variables at a single time point, accurately identifies loss of beta cell function in type 1 diabetes and is comparable to CP AVE for identifying treatment effects. CP EST could serve as a convenient and economical measure of beta cell function in the clinic and as a primary outcome measure in trials of disease-modifying therapy in type 1 diabetes.

Background/objective: Adolescents with type 1 diabetes have early macrovascular changes (increased intima-media thickness [IMT]) and early retinal changes that predict clinical disease in adulthood. We hypothesized that early changes in the macrovascular and retinal microvascular beds develop in parallel before retinopathy develops. We therefore aimed to investigate the relationship between changes in atherosclerosis (carotid and aortic IMT) and retinal vascular geometry cross-sectionally and longitudinally in adolescents with type 1 diabetes., Methods: Ninety adolescents with type 1 diabetes (41 boys, aged 13.6 ± 3.5 years) who were enrolled in a randomized controlled trial had evaluations at baseline; 41 randomized to placebo were also investigated at 12 months for carotid and aortic IMT using ultrasound and retinal vascular geometry was measured from retinal photographs., Results: There were significant associations between thicker mean/maximum carotid IMT and wider retinal arteriolar and venular calibers; for every 0.1 mm increase in mean carotid IMT, retinal arteriolar caliber increased by 7.90 μm (95% confidence interval [CI] 4.50, 11.30, P < 0.0001) and venular caliber by 9.61 μm (95% CI 4.16, 15.06, P = 0.0008). Increased mean aortic IMT was associated with increased arteriolar tortuosity (2.61, 95% CI 0.50, 4.71, P = 0.02)., Conclusions: The early changes of atherosclerosis are associated with retinal microvascular changes in adolescents with type 1 diabetes. This supports parallel adverse changes in the macro and microvascular circulations from early adolescence in type 1 diabetes, and highlights the importance of early intervention., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One purpose of a longitudinal study is to gain insight of how characteristics at earlier points in time can impact on subsequent outcomes. Typically, the outcome variable varies over time and the data for each individual can be used to form a discrete path of measurements, that is a trajectory. Group-based trajectory modelling methods seek to identify subgroups of individuals within a population with trajectories that are more similar to each other than to trajectories in distinct groups. An approach to modelling the influence of covariates measured at earlier time points in the group-based setting is to consider models wherein these covariates affect the group membership probabilities. Models in which prior covariates impact the trajectories directly are also possible but are not considered here. In the present study, we compared six different methods for estimating the effect of covariates on the group membership probabilities, which have different approaches to account for the uncertainty in the group membership assignment. We found that when investigating the effect of one or several covariates on a group-based trajectory model, the full likelihood approach minimized the bias in the estimate of the covariate effect. In this '1-step' approach, the estimation of the effect of covariates and the trajectory model are carried out simultaneously. Of the '3-step' approaches, where the effect of the covariates is assessed subsequent to the estimation of the group-based trajectory model, only Vermunt's improved 3 step resulted in bias estimates similar in size to the full likelihood approach. The remaining methods considered resulted in considerably higher bias in the covariate effect estimates and should not be used. In addition to the bias empirically demonstrated for the probability regression approach, we have shown analytically that it is biased in general.

Background and Objective: Children with type 1 diabetes (T1D) have vascular dysfunction and frequently struggle to adhere to dietary recommendations. Limited data exist for the vascular consequences of poor diet quality in children. We aimed to evaluate the association between dietary components and vascular function in children with T1D., Methods: Cross-sectional study including 90 children (13.6 [3.5] years, 41 boys) with T1D. They had evaluation of dietary micro and macronutrients (Australian Child and Adolescent Eating Survey), vascular endothelial and smooth muscle function (flow-mediated dilatation and glyceryl trinitrate mediated dilatation [GTN], respectively), clinical and biochemical variables., Results: Children had a sodium intake of 3.013 (0.76) (mean [SD]) g/day. Vascular smooth muscle dysfunction, as measured by GTN, related to higher daily sodium intake (r = -0.31, P = .003), independent of the inverse relationships between GTN and total energy (r = -0.30, P = .005) and fat intake (r = -0.28, P = .007). Multiregression model showed that an increase in 1 g of daily sodium intake was independently associated with a deterioration of 3 percentage units in GTN (95% CI -4.3, -0.9; P = .003). There was an association between sodium intake and systolic blood pressure after adjustment for age and gender (regression coefficient 2.4; 95% CI 0.5, 4.3; P = .01)., Conclusions: High dietary sodium intake in children with T1D is common and relates to vascular dysfunction, independently of other dietary intake, blood pressure, and glycemic control., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON; n = 49), from PR pregnancies without intervention (PR; n = 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR + Methyl; n = 25). Both PR and PR + Methyl progeny were smaller than CON; supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA; P < 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR + Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR + Methyl than in PR or CON (each P < 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.

Context: Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis. Early interventions are needed to reduce cardiovascular disease., Objective: To evaluate the effect of metformin on vascular function in children with type 1 diabetes., Design: Twelve-month double-blind, randomized, placebo-controlled trial., Setting: Tertiary pediatric diabetes clinic., Participants: Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI), with type 1 diabetes., Intervention: Metformin (up to 1 g twice a day) or placebo., Main Outcome Measure: Vascular function measured by brachial artery ultrasound [flow-mediated dilatation/glyceryl trinitrate-mediated dilatation (GTN)]., Results: Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45 per group], 10 discontinued intervention, and 1 was lost to follow-up. On metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3 percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or other cardiovascular risk factors. Median (95% CI) adherence, evaluated by electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis., Conclusions: Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children. These benefits and good safety profile warrant further consideration of its use., (Copyright © 2017 Endocrine Society)

Campylobacter spp. is a commonly reported food-borne disease with major consequences for morbidity. In conjunction with predicted increases in temperature, proliferation in the survival of microorganisms in hotter environments is expected. This is likely to lead, in turn, to an increase in contamination of food and water and a rise in numbers of cases of infectious gastroenteritis. This study assessed the relationship of Campylobacter spp. with temperature and heatwaves, in Adelaide, South Australia. We estimated the effect of (i) maximum temperature and (ii) heatwaves on daily Campylobacter cases during the warm seasons (1 October to 31 March) from 1990 to 2012 using Poisson regression models. There was no evidence of a substantive effect of maximum temperature per 1 °C rise (incidence rate ratio (IRR) 0·995, 95% confidence interval (95% CI) 0·993-0·997) nor heatwaves (IRR 0·906, 95% CI 0·800-1·026) on Campylobacter cases. In relation to heatwave intensity, which is the daily maximum temperature during a heatwave, notifications decreased by 19% within a temperature range of 39-40·9 °C (IRR 0·811, 95% CI 0·692-0·952). We found little evidence of an increase in risk and lack of association between Campylobacter cases and temperature or heatwaves in the warm seasons. Heatwave intensity may play a role in that notifications decreased with higher temperatures. Further examination of the role of behavioural and environmental factors in an effort to reduce the risk of increased Campylobacter cases is warranted.