Evaluation of the reach and impact of a UK campaign highlighting obesity as a cause of cancer among the general public and Members of Parliament.

OBJECTIVES: 'Overweight and obesity' is the second biggest preventable cause of cancer after smoking. In 2018, Cancer Research UK launched an awareness raising campaign about the link between overweight and obesity and cancer risk. This study aimed to evaluate the reach and impact of the campaign. STUDY DESIGN: This study was a repeated cross-sectional online survey. METHODS: The campaign consisted of six elements including the main message that 'Obesity is a cause of cancer'. UK adults and Members of Parliament (MPs) were surveyed before the campaign (W1; n = 2124 and n = 151), 1 month (W2; n = 2050 and n = 151) and 3 months after the campaign (W3; n = 2059 and MPs not surveyed). Outcome measures were campaign reach, awareness of overweight and obesity as risk factors for cancer, attitudes towards individuals who are overweight or obese, support for policies to reduce obesity and reactions to the campaign. RESULTS: Overall, 76.2% of MPs and just under half of the public (47.5% in W2 and 36.8% in W3) reported having seen the campaign. Unprompted awareness of obesity as a risk factor increased among the public from 17.1% at W1 to 43.3% in W2 (odds ratio 3.71, 95% confidence interval 3.18-4.33) and 30.3% in W3 (odds ratio 2.11, 95% confidence interval 1.80-2.47). A similar pattern was seen for prompted awareness and among MPs. There were no consistent changes in attitudes towards overweight individuals or support for policies to reduce obesity. CONCLUSIONS: This evaluation suggests that the campaign achieved the primary objective of increasing awareness of the link between obesity and cancer without increasing negative attitudes towards individuals who are overweight or obese.

A comparison of longitudinal modelling approaches: Alcohol and cannabis use from adolescence to young adulthood.

BACKGROUND: Modelling trajectories of substance use over time is complex and requires judicious choices from a number of modelling approaches. In this study we examine the relative strengths and weakness of latent curve models (LCM), growth mixture modelling (GMM), and latent class growth analysis (LCGA). DESIGN: Data were drawn from the Australian Temperament Project, a 36-year-old community-based longitudinal study that has followed a sample of young Australians from infancy to adulthood across 16 waves of follow-up since 1983. Models were fitted on past month alcohol use (n = 1468) and cannabis use (n = 549) across six waves of data collected from age 13-14 to 27-28 years. FINDINGS: Of the three model types, GMMs were the best fit. However, these models were limited given the variance of numerous growth parameters had to be constrained to zero. Additionally, both the GMM and LCGA solutions had low entropy. The negative binomial LCMs provided a relatively well-fitting solution with fewer drawbacks in terms of growth parameter estimation and entropy issues. In all cases, model fit was enhanced when using a negative binomial distribution. CONCLUSIONS: Substance use researchers would benefit from adopting a complimentary framework by exploring both LCMs and mixture approaches, in light of the relative strengths and weaknesses as identified. Additionally, the distribution of data should inform modelling decisions.

Predicting common maternal postpartum complications: leveraging health administrative data and machine learning.

OBJECTIVE: We aimed to predict the risk of common maternal postpartum complications requiring an inpatient episode of care. DESIGN AND SETTING: Maternal data from the beginning of gestation up to and including the delivery, and neonatal data recorded at delivery, were used to predict postpartum complications. SAMPLE: Administrative health data of all inpatient live births (n = 422 509) in the Australian state of Queensland between January 2009 and October 2015. METHOD: Gradient boosted trees were used with five-fold cross-validation to compare model performance. The best performing models for each outcome were then assessed in the independent validation data using the area under the receiver operating curve (AUC-ROC). MAIN OUTCOME MEASURE: Postpartum complications occurring in the first 12 weeks after delivery requiring hospital admission. RESULTS: Postpartum hypertensive disorders obtained good discrimination in the independent validation data (AUC = 0.879, 95% CI 0.846-0.912), as did obstetric surgical wound infection (AUC = 0.856, 95% CI 0.838-0.873), whereas postpartum sepsis and haemorrhage obtained poor discrimination. CONCLUSIONS: Our study suggests that routinely collected health data have the potential to play an important role in helping determine women's risk of common postpartum complications leading to hospital admission. This information can be presented to clinical staff after delivery to help guide immediate postpartum care, delayed discharge, and post-discharge patient follow up. For such a system to be effective and valued, it must produce accurate predictions, and our findings suggest areas where routine data collection could be strengthened to this end. TWEETABLE ABSTRACT: Improved prediction of maternal postnatal hypertensive disorders and wound infection via machine learning.

The natural history of risky drinking and associated harms from adolescence to young adulthood: findings from the Australian Temperament Project.

BACKGROUND: We aimed to describe the natural history of heavy episodic drinking (HED) and associated harms from adolescence to young adulthood in a large Australian population cohort study. METHOD: The Australian Temperament Project consists of mothers and babies (4-8 months) recruited from Infant Welfare Centres and followed every 2 to 4 years until age 28 years. Analyses were based on data from 1156 young people (497 male; 659 female) surveyed repeatedly at ages 16, 18, 20, 24 and 28 years. We used dual processes latent class growth analysis to estimate trajectories of HED and associated harms, employing a piecewise approach to model the hypothesized rise and subsequent fall across adolescence and the late twenties, respectively. RESULTS: We identified four sex-specific trajectories and observed little evidence of maturing-out across the twenties. In males, a normative pattern of increasing HED across the twenties with little related harm was observed (40% of the male sample). Early and late starter groups that peaked in harms at age 20 years with only minor attenuation in binging thereafter were also observed (6.1% and 35%, respectively). In females, a normative pattern of increasing, but moderate, HED with little related harm was observed (44% of the female sample). Early and late starter groups were also identified (18% and 17%, respectively); however, unlike males, the female late starter group showed a pattern of increasing HED and related harms. CONCLUSIONS: Continued patterns of risky alcohol use and related harms are apparent for both males and females across the twenties.

Real-world costs of ischemic stroke by discharge status.

OBJECTIVE: The objective of this study was to estimate the acute healthcare costs of ischemic stroke during hospitalization and the quarterly all-cause healthcare costs for the first year after discharge by discharge status. METHODS: Adult patients with a hospitalization with a diagnosis of ischemic stroke (ICD-9-CM: 434.xx or 436.xx) between 1 January 2006 and 31 March 2015 were identified from a large US commercial claims database. Patients were classified into three cohorts based on their discharge status from the first stroke hospitalization, i.e. dead at discharge, discharged with disability, or discharged without disability. Third-party (medical and pharmacy) and out-of-pocket costs were adjusted to 2015 USD. RESULTS: A total of 7919 patients dead at discharge, 45,695 patients discharged with disability, and 153,778 patients discharged without disability were included in this analysis. The overall average age was 59.7 years and 52.3% were male. During hospitalization, mean total costs (third-party and out-of-pocket) were $68,370 for patients dead at discharge, $73,903 for patients discharged with disability, and $24,448 for patients discharged without disability (p < .001 for each pairwise comparison); mean third-party costs were $63,605 for patients dead at discharge, $67,861 for patients discharged with disability and $19,267 for patients discharged without disability (p < .001 for each pairwise comparison). During the first year after discharge, mean total costs for patients discharged with disability vs. without disability were $46,850 vs. $30,132 (p < .001). Mean third-party costs for patients discharged with disability vs. without disability were $19,116 vs. $10,976 during the first quarter after discharge, $10,236 vs. $6926 during the second quarter, $8241 vs. $5810 during the third quarter, and $6875 vs. $5292 during the fourth quarter (p < .001 for each quarter). CONCLUSION: The results demonstrated the high economic burden of ischemic stroke, especially among patients discharged with disability with the highest costs incurred during the inpatient stays.

The natural history of internalizing behaviours from adolescence to emerging adulthood: findings from the Australian Temperament Project.

BACKGROUND: The aims of the study were to describe the patterning and persistence of anxiety and depressive symptoms from adolescence to young adulthood and to examine long-term developmental relationships with earlier patterns of internalizing behaviours in childhood. METHOD: We used parallel processes latent growth curve modelling to build trajectories of internalizing from adolescence to adulthood, using seven waves of follow-ups (ages 11-27 years) from 1406 participants of the Australian Temperament Project. We then used latent factors to capture the stability of maternal reported child internalizing symptoms across three waves of early childhood follow-ups (ages 5, 7 and 9 years), and examined relationships among these patterns of symptoms across the three developmental periods, adjusting for gender and socio-economic status. RESULTS: We observed strong continuity in depressive symptoms from adolescence to young adulthood. In contrast, adolescent anxiety was not persistent across the same period, nor was it related to later depressive symptoms. Anxiety was, however, related to non-specific stress in young adulthood, but only moderately so. Although childhood internalizing was related to adolescent and adult profiles, the associations were weak and indirect by adulthood, suggesting that other factors are important in the development of internalizing symptoms. CONCLUSIONS: Once established, adolescent depressive symptoms are not only strongly persistent, but also have the potential to differentiate into anxiety in young adulthood. Relationships with childhood internalizing symptoms are weak, suggesting that early adolescence may be an important period for targeted intervention, but also that further research into the childhood origins of internalizing behaviours is needed.

Generational increase in obesity among young women: a prospective analysis of mother-daughter dyads.

BACKGROUND/OBJECTIVES: Increases in obesity in young adults over recent decades are shown by national survey data but have yet to be replicated using prospective data. We aim to quantify the increase in obesity and overweight over two generations of young adult women using prospective measures of body mass index (BMI). SUBJECTS/METHODS: Data are from the Mater University Study of Pregnancy (MUSP), a prospective pre-birth cohort study started in 1981 in Brisbane, Australia. Analyses were restricted to 992 mother-daughter dyads who were at similar ages at the time they were assessed and for whom measures of BMI were available. We also conducted an additional analysis to test whether there was a similar increase amongst father-son dyads. We used multinomial logistic regression for clustered data to compare the same prospective measures of BMI categories between mother and daughters. RESULTS: Controlling for a number of sociodemographic and lifestyle factors in the female sample, daughters had 5.04 (3.03, 8.85) times the odds of being obese and 2.54 (1.86, 3.54) times the odds of being overweight compared with their mothers. A large increase in obesity was also observed in the male sample. CONCLUSIONS: Using a longitudinal design to partly account for familial confounding of obesity risk factors, this study confirms a large and concerning increases in obesity rates over two generations of young adults and suggests increases in obesity over the past 20 years may be greater than previously anticipated.

A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - a case of virally induced periodontitis?

We present a 17-year old girl with DOCK-8 deficiency, severe untreated oral HSV-1 infection and associated aggressive periodontitis. DOCK-8 deficiency is a primary immunodeficiency, caused by biallelicloss-of-function mutations in the DOCK8 gene, often leading to severe viral and fungal mucocutaneous infections. Nevertheless, to date DOCK8 has not been associated with severe periodontitis and inflammatory bone loss around teeth. Understanding whether DOCK8 deficiency or severe HSV-1 infection underlies susceptibility to periodontitis is central to this case and may provide insights into susceptibility factors for periodontitis in the general population. Our clinical and microbiological data suggest that severe HSV-1 infection is the driver of periodontal inflammation in this case.

Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response.

BACKGROUND: Multiple biological therapies are approved for the treatment of moderate-to-severe psoriasis. OBJECTIVES: To assess the short-term efficacy of biological treatments for moderate-to-severe psoriasis via a network meta-analysis that adjusts for reference arm response rates. METHODS: Fifteen randomized trials of biological treatments for moderate-to-severe psoriasis were identified. Rates of response, assessed as 50%, 75% and 90% reductions in the Psoriasis Area and Severity Index (PASI), were compared using a network meta-analysis. To account for variation across trials, the model was adjusted for placebo responses, the relevance of which was assessed by testing its statistical significance, impact on model fit, and extent to which lack of adjustment confounded the efficacy estimates for biologics. RESULTS: Psoriasis Area and Severity Index 75 response rates for placebo arms ranged from 1·8% to 18·9%. The probability of achieving a PASI 75 response was 80·5% [95% credible interval (CrI) 74·8-85·7] with infliximab 5 mg kg(-1) ; 72·5% (95% CI 66·1-78·3) with ustekinumab 90 mg; 67·5% (95% CI 60·7-73·9) with ustekinumab 45 mg; 66·2% (95% CI 57·3-73·3) with adalimumab 40 mg; 51·9% (95% CI 45·7-58·4) with etanercept 50 mg; and 38·0% (95% CI 31·6-45·1) with etanercept 25 mg. Infliximab had the highest PASI 75 response. Adalimumab and both ustekinumab doses had significantly higher PASI 75 responses than both etanercept doses. There were no significant differences among adalimumab and ustekinumab doses. CONCLUSIONS: A model adjusted for reference arm response rates was found to fit clinical trial data significantly better than unadjusted models.

The role of parental alcohol use, parental discipline and antisocial behaviour on adolescent drinking trajectories.

BACKGROUNDS: Parental drinking, harsh parental discipline and adolescent antisocial behaviour have been independently implicated in adolescent alcohol use. Robust prospective studies are required to examine developmental relationships between these factors and their effect on trajectories of alcohol use across adolescence. METHODS: Data were ascertained at three consecutive adolescent waves (13.5, 15.5 and 17.5 years) from the Australian Temperament Project, a 15-wave (30 year) general population birth cohort in Victoria, Australia. Adolescent alcohol trajectories, adjusted for time-varying measures of parenting and antisocial behaviour, were regressed on time-stable measures of parental alcohol use. The full case analysis comprised 751 individuals with complete data. RESULTS: Two distinct alcohol trajectories were identified across the three adolescent waves after adjusting for time-varying factors: a higher and lower drinking group. Both trajectories increased linearly over the study period. Antisocial behaviour was positively associated with both trajectories while harsh parental discipline was positively associated with alcohol use in the lower-use group only. Increased maternal and paternal drinking at 13.5 years placed teenagers at a greater risk of being included in the high-risk trajectory. CONCLUSION: Parental drinking was the strongest predictor of different drinking trajectories in adolescence. This finding underscores the importance of comprehensive public heath approaches that target both parental and adolescent drinking attitudes and behaviour.

[Possible role of alkylphosphocholines in retinal reattachment surgery]. / Mögliche rolle von alkylphosphocholinen bei der ablatio-chirurgie.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a major complication after retinal detachment surgery, but there is no established pharmacotherapy available to control the cell biology of the disease. The aim of this study was to investigate the role of alkylphosphocholines [APCs; erucylphosphocholine (ErPC) was used in this study], novel pharmacologic substances with antiproliferative properties, on intraretinal proliferation initiated by experimental retinal detachment in a well-established in vivo model. METHODS: Retinal detachments were created in adult pigmented rabbits. ErPC was injected intravitreally on either day 1 or day 2 after detachment. Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) was injected on day 3. Following fixation, retinas were triple-labelled with anti-BrdU (proliferation marker), Isolectin B4 (retinal microglia marker), and anti-vimentin (retinal Mueller glia cell marker). The number of anti-BrdU-labelled cells per millimeter of retina was determined from sections imaged by laser scanning confocal microscopy. Toxicity was assessed by light and electron microscopy. RESULTS: A single intravitreal injection of ErPC had a significant effect on reducing the number of proliferating non-neural retinal cells on day 3 after experimental retinal detachment in the rabbit. Injection of ErPC on day 1 was more effective than when given on day 2. No evidence of toxicity was observed in the retina on day 3 for any of the conditions. CONCLUSIONS: APCs are novel pharmacologic substances that significantly inhibited intraretinal proliferation after experimental retinal detachment in this in vivo model. They could be considered as an adjunct therapy at the time of retinal reattachment surgery to potentially prevent proliferative vitreoretinal diseases such as PVR. However, long-term toxicity studies must be performed before APCs can be considered for clinical application.

Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.

Polymorphisms in the complement factor H gene (CFH) are associated with a significantly increased risk for, or protection against, the development of age-related macular degeneration (AMD). The most documented risk-conferring single-nucleotide polymorphism results in a tyrosine-to-histidine substitution at position 402 (Y402H) of the CFH protein. In this work, we examined the ocular distributions and relative abundance of CFH, several CFH-binding proteins, and abundant serum proteins in the retinal pigmented epithelium (RPE), Bruch's membrane, and choroid (RPE-choroid) in CFH homozygotes possessing either the "at-risk" 402HH or "normal" 402YY variants. Although CFH immunoreactivity is high in the choroid and in drusen, no differences in CFH-labeling patterns between genotypes are apparent. In contrast, at-risk individuals have significantly higher levels of the CFH-binding protein, C-reactive protein (CRP), in the choroidal stroma. Immunoblots confirm that at-risk individuals have approximately 2.5-fold higher levels of CRP in the RPE-choroid; no significant differences in the levels of CFH or other serum proteins are detected. Similarly, we find no differences in CFH transcription levels in the RPE-choroid nor evidence for local ocular CRP transcription. Increased levels of CRP in the choroid may reflect a state of chronic inflammation that is a by-product of attenuated CFH complement-inhibitory activity in those who possess the CFH at-risk allele. Because the CRP-binding site in CFH lies within the domain containing the Y402H polymorphism, it is also possible that the AMD risk-conferring allele alters the binding properties of CFH, thereby leading to choroidal CRP deposition, contributing to AMD pathogenesis.