Large Australian Cohort Research Articles

Aortic dimensions in a large Australian adult cohort. New normal range?

Abstract Background There is little published data worldwide about the normal range of aortic dimensions in adults. Guidelines for dilated aortic dimensions and recommendations for surgery are based on small population cohorts and absolute values. Adjustment for BSA and height are becoming more accepted, however the normal range of aortic dimensions for a large population has not been previously published. We present the distribution of aortic dimensions in a large Australian population, with indexation for BSA and height as well as centiles of age. Methods All patients >18 years of age attending for routine echocardiography at our institution from 2007-2022 were included in the database. Measurements of aortic root, sinotubular junction and ascending aorta using ASE criteria were collated. Dimensions were adjusted for BSA and height. Data was analysed for centiles of weight and height and across decades of age. Results A total of 117,912 patients were included in the analysis, aged 62.8+17.6 years (range 18-107), 59% male, 83.7+21.1 kgs (range 32-337) and 169.8+10.3 cm (range 107-218). The aortic root and ascending aortic dimensions are presented in absolute values (average + SD), and height adjusted (cm/m) and BSA adjusted (cm/m2) values. Data was expressed per centile of height, age and weight. There was a progressive increase in aortic dimensions as expected for increasing height, however a robust relationship was identified when dimensions were indexed according to height at all centiles regardless of age and body weight. In contrast, when adjusted for BSA, the aortic dimensions were progressively and predictably under-reported in patients over 80kg for assessment for normal vs dilated. When analysed for centiles of age, there was a small progressive increase in dimensions observed with increasing age. The indexation for height was independently robust across patients of all centiles of height. Conclusion Aortic dimensions are consistently 2.0+0.5 cm/m when adjusted for patient height across all body weight and age centiles. Adjustment for BSA in patients over 80kg tends to under-represent aortic dimensions when assessing for dilatation. Dimensions tend to increase gently with increasing age. We propose a new nomogram for normal aortic dimensions in adults.

Trauma, resilience and significant relationships: Sex differences in protective factors for military mental health.

Military service is historically a male-dominated occupation, as such, the majority of research examining the development of mental disorder in Australian Defence Force members has had primarily male samples. While there have been mixed findings internationally regarding sex differences in rates of mental disorder and subthreshold symptoms among military personnel, across studies, the evidence tends to suggest that female military members are at least as likely as males to experience subthreshold mental health symptoms and have similar or higher rates of posttraumatic stress disorder despite the differences in roles during service. What is less understood is the impact of sex differences in symptom emergence over time and in predictors of clinical disorder. The sample included a longitudinal cohort of Australian Defence Force members (N = 8497) surveyed at Time 1 (2010) and followed up at Time 2 (2015) on measures of anger, self-perceived resilience, trauma exposure, deployment exposure, suicidality, help-seeking, relationship satisfaction and mental health disorder symptoms. Outcomes included Subthreshold Disorder (above the optimal screening cut-off on the 10-item Kessler distress scale or posttraumatic stress disorder checklist) and Probable Disorder (above the epidemiological cut-off on the 10-item Kessler distress scale or posttraumatic stress disorder checklist). Results found that while lifetime trauma exposure remained the strongest predictor of later probable disorder emergence among both males and females, for females specifically, self-reported resilience was also a significant protective factor. In contrast, being in a significant relationship at Time 1 was a protective factor against the development of subthreshold disorder in males. For the first time, sex differences in mental health symptom emergence over time have been explored in a large Australian cohort of military members. The capacity to adapt and bounce back after adversity emerged as a proactive factor against poor mental health for females in the military and could be addressed as part of routine skills training. Social support from significant relationship was particularly important for males' mental health, suggesting that maintaining positive relationships and supporting military spouses and partners are critical for males' mental health.

Individual Resilience and Disaster-Specific Adaptation and Resilience Following a Bushfire Event in Regional Queensland

Natural disasters such as bushfires are a test of individual and group resilience, and in extreme cases, threaten the sustainability of communities. Bushfires have long been common in Australia, although anthropogenic climate change has exacerbated their prevalence and severity. The aim of the present study was to assess the individual resilience and disaster-specific adaptation and resilience of community members in the wake of a bushfire event. Using a quantitative, cross-sectional design, an adult community sample of 165 residents of Noosa Shire in regional Queensland, Australia completed the 25-item Connor-Davidson Resilience Scale (CD-RISC©) and the 43-item Disaster Adaptation and Resilience Scale (DARS). Mean scores for the CD-RISC© indicated significantly greater resilience (p < 0.001) than reported previously for a large Australian community cohort. Similarly, the DARS scores indicated significantly greater adaptation and resilience (p < 0.001) than that of a comparable cohort in the USA. The two oldest groups of residents (66+ years and 51–65 years) reported significantly greater adaptation and resilience than the group of younger residents (≤50 years; p < 0.001). The study findings provide the Noosa Shire community with an objective baseline from which they can assess the efficacy of future resilience-building initiatives and, more broadly, offer a valuable point of reference for future disaster-related research.

Ascending Aortic Dimensions From a Large Australian Adult Cohort. Should We be Indexing by Height Not BSA?

Ascending Aortic Dimensions From a Large Australian Adult Cohort. Should We be Indexing by Height Not BSA?

Impact of bronchodilator responsiveness classification changes on a large Australian community cohort

RATIONALE Bronchodilator responsiveness (BDR) was redefined in the 2021 European Respiratory Society/American Thoracic Society (ERS-ATS) technical statement, from at least 200 mL absolute and 12% relative change in forced expiratory volume in 1 sec (FEV1) or forced vital capacity (FVC) in 2005 to more than 10% change from predicted values. OBJECTIVES The objectives of this research are to measure the impact of BDR reclassification and identify the characteristics of reclassified patients. METHODS A retrospective cohort analysis of a convenience sample of 2,065 tests. Repeat tests were excluded. MEASUREMENTS AND MAIN RESULTS A total of 1,429 tests were evaluated; 206 (14%) were BDR by one or both definitions; and 55/206 (27%) of these records were reclassified, with a close number of results newly classified as BDR (n = 27) and losing this classification (n = 28). Analyzing FEV1 only, 159 tests were BDR by one or both definitions; and 48/159 (30%) were reclassified, with 18 newly classified as BDR and 30 losing this classification. Analyzing FVC only, 101 tests were BDR by one or both definitions; and 27/101 (27%) were reclassified, with 19 newly classified as BDR and 8 losing this classification. Individuals with BDR that were reclassified were significantly heavier (81.8 vs 75.8 kg), and taller (170.6 vs 166.1 cm), although there was no significant difference in body mass index (BMI) (27.9 vs 27.3 kg/m2). They had smaller relative changes in FEV1 (12% vs 16%) and FVC (6% vs 12%), and greater baseline FEV1 (1.99 vs 1.74 L) and FVC (3.39 vs 2.97 L) and were more likely to be female (59% vs 42%). CONCLUSIONS More people were reclassified than expected. When evaluated by expiratory maneuver, there were less people classified as BDR using FEV1 in 2021 than 2005, and more using FVC. This analysis illustrates the potential clinical impact of the change in BDR definition.

Long-Term Implications of Socioeconomic Status on Major Adverse Cardiovascular, Cerebrovascular Events (MACCE), and All-Cause Mortality

Socio-economic status (SES) has a large impact on health through a complex interplay of upstream, midstream and downstream factors. However, little is known about the predictive role of SES on long-term major adverse cardiovascular, cerebrovascular events, and mortality (MACCE). To determine the long-term relationship between SES and MACCE for men and women. The secondary endpoint was to determine the relationship between SES and all-cause mortality. A total of 3,034 participants (1,494 women and 1,540 men) were assessed at baseline in the Geelong Osteoporosis Study, a large regional Australian population cohort study. Area-based SES was assessed, utilising the Index of Relative Socio-Economic Disadvantage (IRSD) and grouped into quintiles. The primary endpoint, MACCE, was defined as a composite of myocardial infarction, heart failure hospitalisation, malignant arrhythmias, stroke, and all-cause mortality. The secondary endpoint was all-cause mortality. Baseline data including age, sex, smoking status and alcohol use, and comorbidities were collected between 1993-1997 for women, and 2001-2006 for men, with follow-up over 30 and 22 years, respectively. Logistic regression was utilised to assess MACCE and all-cause mortality outcomes across the SES quintiles. Participants lost to follow-up or with incomplete data collection were excluded leaving 2,173 participants eligible for analysis. SES was associated with MACCE outcomes. Compared with Quintile I (lowest SES stratum), the odds of MACCE for each IRSD stratum were: Quintile II, odds ratio (OR) 0.85 (95% confidence interval [CI] 0.65-1.13); Quintile III, OR 0.69 (95% CI 0.51-0.91); Quintile IV, OR 0.66 (95% CI 0.50-0.88); and, Quintile V, OR 0.55 (95% CI 0.41-0.72). In the adjusted model, an inverse trend was noted, with reducing MACCE outcomes with an increasing SES status; IRSD Quintile II, OR 0.85 (95% CI 0.62-1.17); Quintile III, OR 0.70 (95% CI 0.50-0.97); Quintile IV, OR 0.73 (95% CI 0.52-1.02); and, Quintile V, OR 0.54 (95% CI 0.39-0.74). SES was inversely associated with all-cause mortality; IRSD Quintile II (OR 0.87, 95% CI 0.66-1.16) failed to achieve significance however IRSD Quintile III (OR 0.65, 95% CI 0.48-0.88), Quintile IV (OR 0.59, 95% CI 0.44-0.80) and Quintile V (OR 0.46, 95% CI 0.34-0.62) had a lower risk of mortality compared with Quintile I. In the adjusted model, an inversely proportional trend was noted between SES and all-cause mortality; IRSD Quintile II (OR 0.82, 95% CI 0.59-1.15), IRSD Quintile III (OR 0.63, 95% CI 0.49-0.95), Quintile IV (OR 0.59, 95% CI 0.45-0.90) and Quintile V (OR 0.44, 95% CI 0.31-0.61) had fewer mortality events compared with IRSD Quintile I. Our research indicates that being part of a lower socio-economic stratum is linked to a higher likelihood of experiencing negative cardiovascular and cerebrovascular events, along with an increased risk of overall mortality. SES is an important risk stratification marker for long-term prognosis of cardiovascular diseases and stroke, and warrants further investigation.

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study

BackgroundThe aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. MethodsThis was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000–2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests.Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. FindingsThe final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0·19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13·2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0·74%), with the highest rate (19·6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7·59% livebirths), with the peak incidence occurring in the <1st centile category (12·3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10–90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. InterpretationAlthough the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently “appropriately grown” (i.e., birthweight 10th - 90th centile). FundingNational Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women’s Health Foundation – Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

P084 Characteristics of sleep hypoventilation during polysomnography in a large Australian clinical sleep laboratory cohort.

Abstract BACKGROUND Sleep hypoventilation complicates a range of neurological and respiratory conditions. However, robust definitions are based mainly on expert consensus, and clinically significant thresholds remain unclear. This study thus aims to provide a descriptive analysis of capnography results in a large clinical cohort of patients referred for overnight polysomnography (PSG). METHODS Retrospective clinical audit of overnight in-lab PSGs, between Jan 2015 and June 2023, at a tertiary hospital housing the State-wide referral centre for chronic domiciliary ventilation. Diagnostic PSGs with transcutaneous CO2 (PTcCO2) monitoring and without supplemental oxygen were included. The following data will be extracted from each PSG: Patient demographics: -Primary and secondary clinical diagnoses -PTcCO2 values (e.g. Mean, Minimum and Maximum PTcCO2 in Wake, Sleep, NREM and REM) -Sleep fragmentation measures -Sleep macro-architecture measures -AHI -SpO2 values Data analysis will be performed with IBM SPSS Statistics software, version 26 (Armonk, NY: IBM Corp) PROGRESS TO DATE 525 PSGs meeting initial criteria have been identified. Currently processing PSG data files to extract parameters and complete exploratory data cleaning and analysis. INTENDED OUTCOME AND IMPACT We aim to explore and clarify: -Differences in patterns of hypoventilation between different diagnostic groups. -Relationships between awake hypoventilation, sleep hypoventilation and REM-isolated hypoventilation. -Effects of applying differing criteria for hypoventilation available in the literature. -Relationships between measures of sleep fragmentation, AHI, SpO2 and hypoventilation parameters. The results of this study will also support and inform future research into associations between severity, duration and patterns of hypoventilation and clinically significant outcomes including morbidity and mortality.

Disease-modifying therapies do not affect sleep quality or daytime sleepiness in a large Australian MS cohort.

Poor sleep is common in multiple sclerosis (MS) and may impact daily functioning. The extent to which disease-modifying therapies (DMTs) contribute to sleep outcomes is under-examined. To compare the effects of DMTs on sleep outcomes in an Australian cohort of people with MS and investigate associations between DMT use and beliefs about sleep problems and daily functioning (social functioning and activity engagement). Sleep outcomes were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. DMT use and functioning were self-reported. Of 1,715 participants, 64% used a DMT. No differences in sleep outcomes were detected between participants who did and did not use DMTs, the type of DMT used (lower vs higher efficacy, interferon-β vs other DMTs), the timing of administration, or adherence to standard administration recommendations. Beliefs that DMT use worsened sleep were associated with poorer sleep quality and perceptions that sleep problems interfered with daily functioning. The use of a DMT does not appear to affect self-reported sleep outcomes in people with MS. However, beliefs that DMT use makes sleep worse were associated with poorer sleep quality and increased interference in daily functioning, suggesting a need for education to diminish negative perceptions of DMT use.

Coronavirus disease 2019 outcomes in heart transplant recipients: A large Australian cohort

Heart transplant recipients have been reported to be at a significantly elevated risk of poor outcomes from coronavirus disease 2019 (COVID-19) infection owing to their underlying comorbidities and immunosuppression. We conducted a single-center retrospective cohort of all heart transplant recipients who were known to have contracted COVID-19 between January 2020 and September 2022. Electronic medical records were used to collect baseline demographics, vaccination status, COVID-19 treatment received, hospitalization data, and mortality. Our primary end point was mortality, and our secondary endpoint was hospitalization. Between January 2020 and September 2022, 132 heart transplant recipients at our single-center contracted COVID-19 infection. Our population had high rates of vaccination, with 124 patients (94%) having received at least 2 vaccines. We found significantly lower rates of mortality and hospitalization than had been previously reported earlier in the pandemic, with a mortality rate of 8/132 (6%) and hospitalization rate of 21/132 (16%).

Burden of disease and real-world treatment patterns of patients with systemic lupus erythematosus in the Australian OPAL dataset

ObjectiveTo describe the demographics, disease burden and real-world management of patients with systemic lupus erythematosus (SLE) in Australian community practice.MethodsPatients with a physician diagnosis of SLE and at least 1 visit between 1 January 2009 and 31 March 2021 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 112 Australian rheumatologists. Demographics, basic clinical features and prescribed medications were described, with medication combinations used as a surrogate of disease severity.ResultsOf 5133 patients with a diagnosis of lupus, 4260 (83%) had SLE. Of these SLE patients, almost 90% of patients were female, with a median age of 49 years [IQR 37–61] at first-recorded visit. Of the 2285 SLE patients whose most recent visit was between 1 January 2019 and 31 March 2021, 52.5% had mild disease, 29.9% had moderate-severe disease and 7.4% had very severe disease. Visit frequency increased with disease severity. Most patients (85.8%) were treated with hydroxychloroquine, typically prescribed as first line-of-therapy.ConclusionIn this large real-world Australian cohort of patients with SLE, a substantial burden of disease was identified, with a significant proportion (almost one-third of patients) considered to have moderate to severe disease based on medication use. This study provides a greater understanding of the path from symptom onset to treatment and the heterogeneous presentation of patients with SLE who are treated in community practice in Australia.Key messages• Most published studies describing patients with SLE are derived from specialist lupus centres, typically in the hospital setting, therefore little is known about the characteristics of patients with SLE who are receiving routine care in community clinics.• The OPAL dataset is a large collection of clinical data from the electronic medical records of rheumatologists predominantly practising in private community clinics, which is where the majority (73–80%) of adult rheumatology services are conducted in Australia [1–3] . Since data from community care has not been widely available for SLE research, this study contributes important insight into this large and under-reported patient population.• To improve access to care and effective treatments, and reduce the burden of SLE in Australia, a greater understanding of the characteristics and unmet needs of patients with SLE managed in the community setting is required.

Does OSA Increase Risk for Cancer?: A Large Historical Sleep Clinic Cohort Study

The relationship between OSA and cancer is unclear. What is the association between OSA and cancer prevalence and incidence in a large Western Australian sleep clinic cohort (N= 20,289)? OSA severity was defined by apnea-hypopnea index (AHI) and nocturnal hypoxemia (duration and percentage at oxygen saturation< 90%) measured by in-laboratory polysomnogram. Measures of potential confounding included age, sex, BMI, smoking, socioeconomic status, and BP. Outcomes were determined from the Western Australian cancer and death registries. Analyses were confined within periods using consistent AHI scoring criteria: January 1, 1989, to July 31, 2002 (American Sleep Disorders Association [ASDA] criteria), and August 1, 2002, to June 30, 2013 (Chicago criteria). We examined associations of AHI and nocturnal hypoxemia with cancer prevalence using logistic regression and cancer incidence using Cox regression analyses. Cancer prevalence at baseline was 329 of 10,561 in the ASDA period and 633 of 9,728 in the Chicago period. Nocturnal hypoxemia but not AHI was independently associated with prevalent cancer following adjustment for participant age, sex, BMI, smoking, socioeconomic status, and BP. Of those without prevalent cancer, cancer was diagnosed in 1,950 of 10,232 (ASDA) and 623 of 9,095 (Chicago) participants over a median follow-up of 11.2 years. Compared with the reference category (no OSA, AHI< 5 events per hour), univariable models estimated higher hazard ratios for cancer incidence for mild (AHI 5-15 events per hour), moderate (AHI 15.1-30 events per hour), and severe (AHI > 30 events per hour) OSA. Multivariable analyses consistently revealed associations between age and, in some cases, sex, BMI, and smoking status, with cancer incidence. After adjusting for confounders, multivariable models showed no independent association between OSA severity and increased cancer incidence. Nocturnal hypoxemia is independently associated with prevalent cancer. OSA severity is associated with incident cancer, although this association seems secondary to other risk factors for cancer development. OSA is not an independent risk factor for cancer incidence.

Male infants are at higher risk of neonatal mortality and severe morbidity.

While a male infant is usually born with a higher birthweight than his female counterpart, he is more at risk of variety of adverse perinatal outcomes. Indeed, throughout life, females exhibit a marked survival advantage compared to males. The aetiology for such pertinent sex disparity remains unclear and is likely multifactorial. The aim of this study was to investigate obstetric and perinatal outcomes by infant sex from 28 weeks in a contemporary, large Australian birth cohort. A 14-year retrospective cohort study of 130 133 births over 28 weeks gestation from a single tertiary centre. Male infants had overall higher rates of neonatal mortality (0.12% vs 0.06%, P < 0.001) and severe neonatal morbidity (12% vs 9.1%, P < 0.001) (adjusted odds ratio (aOR) 1.41, 95% CI 1.35-1.47). The odds of overall perinatal mortality (stillbirth and neonatal death) were higher for male infants (aOR 1.30, 95% CI 1.08-1.56). The difference in severe neonatal morbidity when stratified by gestational age at birth only remained significant from >35 weeks gestation. Regardless of infant sex, rates of neonatal mortality and morbidity were lowest at 39 weeks gestation. Rates of preterm birth and operative birth were also higher for male infants. Our study demonstrates significant disparities in clinical outcomes by infant sex with males at a disadvantage to female infants.

Alcohol consumption and socioeconomic status associated with the risk of kidney cancer in a large Australian cohort study

PurposeStudies have shown an inverse association between alcohol consumption and kidney cancer risk. We postulate that this inverse association may be further influenced by other risk factors. MethodsWe used an Australian cohort, the 45 and Up Study, recruited between 2005 and 2009 to investigate the association between alcohol consumption, and other potential risk factors and kidney cancer incidence. The median follow-up was 5.4 years. ResultsOf the 267,357 participants aged ≤45 years living in New South Wales, 497 were diagnosed with kidney cancer. There was a significant inverse association between alcohol consumption and risk of kidney cancer (P = .027), and a significant inverse dose–response relationship (P = .011). There was a significant interaction between alcohol consumption and socioeconomic status (P interaction = .001). Participants residing in higher socioeconomic areas (the two most advantaged quintiles) who consumed 8–10 drinks or greater than 10 drinks per week, respectively, had a lower risk of kidney cancer compared to the group who consumed 1–4 drinks per week (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15–0.76, HR 0.51, 95% CI 0.31–0.83) with a dose–response trend of HR 0.62 (95% CI 0.42–0.93) per 7 drink increase in weekly alcohol consumption. ConclusionsThere could be an inverse association between alcohol consumption and risk in those residents in higher socioeconomic areas.

Fracture risk and impact in boys with Duchenne muscular dystrophy: A retrospective cohort study.

Boys with Duchenne muscular dystrophy (DMD) are at increased risk of fracture. This study investigated the incidence of fractures, factors contributing to risk of first fracture with emphasis on body mass index (BMI), and the impact of fractures on functional capacity in an Australian cohort of boys with DMD. A retrospective cohort study included boys with DMD who attended a pediatric neuromuscular clinic from 2011 to 2018. Information regarding fractures, anthropometry measurements, body composition and functional assessment was collected. Factors associated with first fracture risk were analyzed with Cox-proportional hazards. Longitudinal analysis of function post-fracture was also conducted. This study included 155 boys with DMD. At least one fracture occurred in 71 (45%) boys; overall incidence of fractures was 399-per-10,000 persons-years. The first fracture was vertebral in 55%; 41% had non-vertebral fractures and 4% had both. Vertebral fractures occurred in significantly older (12.28 vs 9.28 y) boys with longer exposure to glucocorticoids (5.45 vs 2.50 y) compared to non-vertebral fractures. Boys with a history of fracture(s) had a steeper rate of functional decline (measured by Northstar Ambulatory Assessment score) than those with no recorded fractures. A high fracture burden was observed in a large Australian cohort of boys with DMD. Further investigation is required to understand preventative strategies and modifiable risk factors to reduce the incidence of fractures in DMD. The impact on fractures on ambulatory capacity should be closely monitored.

Dairy Product Consumption and Incident Prediabetes in the Australian Diabetes, Obesity, and Lifestyle Study With 12 Years of Follow-Up

BackgroundInvestigating modifiable risk factors for the early stages of the development of type 2 diabetes is essential for effective prevention. Some studies show protective associations between dairy and prediabetes; however, associations are heterogeneous by the type and fat content of dairy foods. ObjectiveTo examine the relationship between the consumption of dairy, including different types of dairy products and risk of prediabetes. MethodsThe study included 4891 participants with normal glucose tolerance (aged 49.0 ± 12.3 y, 57% female) of the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study, a longitudinal population-based study. Dairy intake was measured at baseline using a food frequency questionnaire. Prediabetes at the 5-y and 12-y follow-ups was defined according to the WHO criteria as fasting plasma glucose levels of 110–125 mg/dL or 2-h plasma glucose levels of 140–199 mg/dL. Associations were analyzed using Poisson regression, adjusted for social demographics, lifestyle behaviors, a family history of diabetes, and food group intake. ResultsIn total, 765 (15.6%) incident cases of prediabetes were observed. The mean intake of dairy foods was 2.4 ± 1.2 servings/d, mostly consisting of low-fat milk (0.70 ± 0.78 servings/d) and high-fat milk (0.47 ± 0.72 servings/d). A higher intake of high-fat dairy (RRservings/d: 0.92; 95% CI: 0.85, 1.00), high-fat milk (0.89; 95% CI: 0.80, 0.99), and total cheese (0.74; 95% CI: 0.56, 0.96) was associated with a lower risk of prediabetes. Low-fat milk intake was associated nonlinearly with prediabetes risk. Low-fat dairy foods, total milk, yogurt, low-fat cheese, and ice cream were not associated with prediabetes risk. ConclusionIn this large Australian cohort, protective associations were found for high-fat dairy types, whereas neutral associations were seen for low-fat dairy types. Studies with more detail on sugar content of types of dairy foods and products eaten with dairy foods (e.g., cereals or jam), and studies into potential causal mechanisms of the health effects of dairy intake are required.

Discretionary food intake and willingness to change in a large Australian cohort: findings from the CSIRO Junk Food Analyser

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Pathways from developmental vulnerabilities in early childhood to schizotypy in middle childhood.

Childhood disturbances in social, emotional, language, motor and cognitive functioning, and schizotypy have each been implicated as precursors of schizophrenia-spectrum disorders. We investigated whether relationships between early childhood developmental vulnerabilities and childhood schizotypy are mediated by educational underachievement in middle childhood. Participants were members of a large Australian (n=19,216) population cohort followed longitudinally. Path analyses were used to model relationships between developmental vulnerabilities at age ~5 years, educational underachievement from ages ~8 to 10 years and three distinct profiles of schizotypy at age ~11 years (true, introverted and affective schizotypy). Early childhood developmental vulnerabilities on five broad domains (related to physical, emotional, social, cognitive and communication development) were associated with schizotypy profiles in middle childhood. Educational underachievement in middle childhood was associated with all schizotypy profiles, but most strongly with the true schizotypy profile (OR=3.92, 95% CI=3.12, 4.91). The relationships between schizotypy profiles and early childhood developmental vulnerabilities in 'language and cognitive skills (school-based)' and 'communication skills and general knowledge' domains were fully mediated by educational underachievement in middle childhood, and the relationships with early childhood 'physical health and well-being' and 'emotional maturity' domains were partially mediated. Developmental continuity from early childhood developmental vulnerabilities to schizotypy in middle childhood is mediated by educational underachievement in middle childhood. While some domains of early developmental functioning showed differential relationships with distinct schizotypy profiles, these findings support a developmental pathway to schizotypy in which cognitive vulnerability operates from early childhood through to middle childhood.

Assessment of immunological anti‐platelet factor 4 antibodies for vaccine‐induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: A multicenter study comprising 1284 patients

BackgroundVaccine‐induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus‐based vaccines aimed to prevent and minimize COVID‐19 and related pathophysiology. ObjectivesTo describe patterns of testing for anti‐platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset. Patients/MethodsAsserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78–179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate; n = 476), and rapid immunological chemiluminescence anti‐PF4 assay (n = 460), in a multicenter study. ResultsFor first episode presentations, 190/1284 (14.8%) ELISA tests were positive. Conversely, most (445/460; 96.7%) chemiluminescence anti‐PF4 test results were negative. All functional assays showed associations of higher median ELISA optical density with functional positivity and with high rates of ELISA positivity (64.0% to 85.2%). Data also identified functional positivity in 14.8%–36.0% of ELISA negative samples, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases. ConclusionTo our knowledge, this is the largest multicenter evaluation of anti‐PF4 testing for investigation of VITT. Discrepancies in test results (ELISA vs. ELISA or ELISA vs. functional assay) in some patients highlighted limitations in relying on single methods (ELISA and functional) for PF4 antibody detection in VITT, and also highlights the variability in phenotypic test presentation and pathomechanism of VITT.

A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years.

Oral medicinal cannabis (MC) has been increasingly prescribed for a wide range of clinical conditions since 2016. Despite an exponential rise in prescriptions and publications, high quality clinical efficacy and safety studies are lacking. The outcomes of a large Australian clinical electronic registry cohort are presented. A prospective cannabis-naïve patient cohort prescribed oral MC participated in an ongoing longitudinal registry at a network of specialised clinics. Patient MC dose, safety and validated outcome data were collected regularly over two years and analysed. 3,961 patients (mean age 56.07 years [SD 19.08], 51.0% female) with multimorbidity (mean diagnoses 5.14 [SD 4.08]) and polypharmacy (mean 6.26 medications [SD 4.61]) were included in this analysis. Clinical indications were for: chronic pain (71.9%), psychiatric (15.4%), neurological (2.1%), and other diagnoses (10.7%). Median total oral daily dose was 10mg for Δ9-tetrahydrocannabinol (THC) and 22.5mg for cannabidiol (CBD). A stable dose was observed for over two years. 37.3% experienced treatment related adverse events. These were graded mild (67%), moderate (31%), severe (<2%, n = 23) and two (0.1%) serious adverse events. Statistically significant improvements at a p value of <0.001 across all outcomes were sustained for over two years, including: clinical global impression (CGI-E, +39%: CGI-I, +52%; p<0.001), pain interference and severity (BPI, 26.1% and 22.2%; p<0.001), mental health (DASS-21, depression 24.5%, anxiety 25.5%, stress 27.7%; p<0.001), insomnia (ISI, 35.0%; p<0.001), and health status (RAND SF36: physical function, 34.4%: emotional well-being, 37.3%; p<0.001). Mean number of concomitant medications did not significantly change over 2 years (p = 0.481). Oral MC was demonstrated to be safe and well-tolerated for a sustained period in a large complex cohort of cannabis-naïve, multimorbid patients with polypharmacy. There was significant improvement (p<0.001) across all measured clinical outcomes over two years. Results are subject to limitations of Real World Data (RWD) for causation and generalisability. Future high quality randomised controlled trials are awaited.