Trends in risk factors for vascular disease in Australia

Data from the National Heart Foundation Risk Factor Prevalence Surveys of 1980 and 1983 were analysed to detect national trends in risk factors for vascular disease in Australia. After statistical adjustment for differences in the demographic characteristics of the two populations of survey participants, our results show trends in smoking and blood pressure that are likely to result in a continuing fall in the incidence of vascular disease. There was a fall in the prevalence of current smoking from 32% to 29% but little change in the average daily consumption of cigarettes by current smokers. The prevalence of previously-undetected hypertension fell significantly from 10% to 7%. A small increase occurred in the proportion of all hypertensive patients who were treated and whose blood pressure was controlled, and a decline of 2.0 mmHg (P less than 0.0001) in mean diastolic blood pressures, but no significant change in mean systolic pressures. Mean total plasma cholesterol levels did not change; average levels of plasma triglycerides fell by 0.11 mmol/L (P less than 0.0001); and mean high-density lipoprotein cholesterol levels increased by 0.03 mol/L (P less than 0.0001). All indices of relative body weight increased between 1980 and 1983; mean body mass index rose by 0.23 with associated rises in the prevalence of obesity and of overweight status. The changes in other factors such as use of added salt, the consumption of alcohol, the level of physical activity and adherence to a special diet, all were in the desirable direction, although minor changes in the survey questionnaire might have served to exaggerate the apparent trends.     

Dandy-Walker malformation (variant), cystic dysplastic kidneys, and hepatic fibrosis: a distinct entity or Meckel syndrome?

Dandy-Walker malformation is an unusual finding in Meckel syndrome, which characteristically presents with encephalocele, polydactyly, and cystic renal disease. We report on a family in which three nonviable brothers had Dandy-Walker malformations (variant) with associated enlarged cystic dysplastic kidneys and hepatic fibrosis. The consistent segregation of these abnormalities in all three sibs in the absence of polydactyly and encephalocele suggested the possibility of a distinct syndrome. The clinicopathological findings of the disorder are described and discussed in the context of the phenotypic spectrum of Meckel syndrome.     

Analysis of myocilin mutations in 1703 glaucoma patients from five different populations

A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.     

Intravenous immunoglobulin significantly reduces exposure of concomitantly administered anti‐C5 monoclonal antibody tesidolumab

Awareness of drug‐drug interactions is critical in organ transplant recipient management. However, biologic agents interfering with monoclonal antibodies is not widely considered. We report the effect of high‐dose intravenous immunoglobulin (IVIg) on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the human anti‐C5 monoclonal antibody tesidolumab (LFG316) in end‐stage renal disease patients awaiting kidney transplant. In this single‐center, phase 1, open‐label, parallel‐group study, 8 patients were assigned to receive either single‐dose tesidolumab + IVIg or tesidolumab alone, with 56‐day follow‐up. Within‐group PK parameters were consistent. Mean tesidolumab exposure decreased 34%, clearance increased 63%, and half‐life decreased 41% comparing tesidolumab + IVIg to tesidolumab alone. IVIg influence on tesidolumab elimination was most evident in the first 3 weeks. Complete suppression of both total and alternative complement activities was maintained for 4 weeks in the tesidolumab alone group and for 2 weeks in the tesidolumab + IVIg group. Tesidolumab was well tolerated. IVIg infused before tesidolumab affected tesidolumab PK and PD, resulting in a shortened period of full complement activity inhibition. These findings suggest a clinically relevant impact of IVIg on monoclonal antibody clearance and indirectly hint at an IVIg mechanism of action in treating autoimmune diseases and allosensitization by accelerating pathogenic IgG antibody degradation. Trial registration number: NCT02878616.     

A comparison of SF-36 summary measures of physical and mental health for women across the life course

Background

Physical and mental component summary scores (PCS and MCS, respectively) are often used to summarise SF-36 quality of life subscales. This paper investigates PCS and MCS across the life course and compares the trajectories obtained from two different methods of calculation.

Methods

The Australian Longitudinal Study on Women’s Health is a population-based study with three cohorts of women and SF-36 surveys taken at multiple time points. Scoring coefficients for each component score were determined using factor analysis with uncorrelated (orthogonal) and correlated (oblique) rotation at the baseline survey, which were then used to compute correlated and uncorrelated PCS and MCS scores at each survey (scaled to have mean of 50 and standard deviation of 10 at baseline).

Results

For both methods, PCS declined progressively across the lifespan, while MCS rose in young and mid-age women to a peak and subsequently declined in later life. Differences were apparent between correlated and uncorrelated scores, most notably for MCS in the older cohort, where correlated MCS reached 54.6 but still less than uncorrelated MCS, with a random effects model indicating 1.63 (95 % confidence intervals 1.58–1.67) units difference; it then declined to a score of 51.2 by the last survey and the difference widened to 3.44 (3.38–3.50) units compared with the uncorrelated MCS.

Conclusions

PCS and MCS have distinct trajectories through life, with differences in results from correlated and uncorrelated component summary scores. The divergence is most notable with MCS, especially for older women, suggesting that correlated MCS and PCS should be used when examining change in health over time in this age group.     

Recruitment via the Internet and Social Networking Sites: The 1989-1995 Cohort of the Australian Longitudinal Study on Women’s Health

BackgroundFaced with the challenge of recruiting young adults for health studies, researchers have increasingly turned to the Internet and social networking sites, such as Facebook, as part of their recruitment strategy. As yet, few large-scale studies are available that report on the characteristics and representativeness of the sample obtained from such recruitment methods.ObjectiveThe intent of the study was to describe the sociodemographic and health characteristics of a national sample of young Australian women recruited mainly through the Internet and social networking sites and to discuss the representativeness of their sociodemographic, health, and lifestyle characteristics relative to the population.MethodsA cohort of 17,069 women (born between 1989 and 1995) was recruited in 2012-13 for the Australian Longitudinal Study on Women’s Health. Sociodemographic characteristics (percentages, means, and 95% confidence intervals) from the online survey data were compared with women aged 18-23 years from the 2011 Australian Census. Sample data were compared by age and education level with data from the 2011-13 Australian Health Survey (AHS).ResultsCompared to the Australian Census data, study participants were broadly representative in terms of geographical distribution across Australia, marital status (95.62%, 16,321/17,069) were never married), and age distribution. A higher percentage had attained university (22.52%, 3844/17,069) and trade/certificate/diploma qualifications (25.94%, 4428/17,069) compared with this age group of women in the national population (9.4% and 21.7% respectively). Among study participants, 22.05% (3721/16,877) were not in paid employment with 35.18% (5931/16,857) studying 16 or more hours a week. A higher percentage of study participants rated their health in the online survey as fair or poor (rather than good, very good, or excellent) compared with those participating in face-to-face interviews in the AHS (18.77%, 3203/17,069 vs 10.1%). A higher percentage of study participants were current smokers (21.78%, 3718/17,069 vs 16.4%) and physically active (59.30%, 10,089/17,014 were classified as sufficiently active vs 48.3%) but alcohol consumption was lower (59.58%, 9865/16,558 reported drinking alcohol at least once per month vs 65.9% in the AHS). Using self-reported height and weight to determine body mass index (BMI, kg/m²), 34.80% (5901/16,956) of the cohort were classified as overweight or obese (BMI of 25 or more), compared with 33.6% respectively using measured height and weight in the AHS.ConclusionsFindings indicated that using the Internet and social networking sites for an online survey represent a feasible recruitment strategy for a national cohort of young women and result in a broadly representative sample of the Australian population.