bluuebunny/crossref_metadata_2025_split huggingface dataset:
1212Examining the relationship between childhood adversity and mental health in older adults
Authors: Lian James , Kiely Kim M. , Anstey Kaarin J. 
Published: September 2021

Abstract

Background
There is a need to understand how early adversity is linked with mental health in older adults. The aim of this study was to 1) explore the optimal way to operationalise a scale of adverse childhood experiences (ACEs) and 2) examine the association between ACEs with depression and anxiety in older adulthood.

Methods
Data were from Wave 1 of the Personality and Total Health (PATH) Through Life Project (N = 7485, 51% women). Older adults aged 60-65 reported their childhood experiences of domestic adversity on a 17-item scale (e.g., physical abuse, neglect, poverty). Depression and anxiety were assessed using four validated screening instruments (GDS, GAS, MCS-12, PHQ-9). Three approaches to scoring the ACE scale were compared: i) cumulative risk, ii) factor analysis, and iii) latent class analysis (LCA). Linear regression models estimated associations between ACEs and mental health, adjusting for age, race, education, and gender.

Results
Childhood adversity was associated with late life depression and anxiety using the cumulative risk approach. Factor analysis produced latent factors of threat and deprivation, which were highly correlated, leading to problems with multicollinearity when estimating associations. Finally, LCA revealed three classes of ACEs: high adversity, low adversity, and parental maladjustment. High adversity and parental maladjustment were associated with higher levels of depression and anxiety symptoms compared to low adversity.

Conclusion
Different approaches to operationalising childhood adversity reveal that ACE exposure is associated with depression and anxiety in older adults. Future studies will utilise these methods to investigate links with cognitive decline and dementia.
198Prevalence of illicit substances in personal vaporisers on online cryptomarkets
Authors: Lim Miss Carmen , Leung Janni , Connor Jason , Hall Wayne , Cheng Brandon , Gartner Coral , Scheurer Roman , Chan Gary 
Published: September 2021

Abstract

Background
Personal vaporisers or e-cigarettes are gaining popularity as an alternative route of administration for illicit substances. Data from the Centers for Disease Control and Prevention on the recent epidemic of vaping related lung injuries has confirmed that victims had vaped blackmarket tetrahydracannabidiol, including some sourced from online cryptomarkets. We examined the diversity and prevalence of illicit substances in vaping products available from these marketplaces.

Methods
Vaping related listings were extracted from three online cryptomarkets (‘Agartha’, ‘Cryptonia’, and ‘Tochka’) using The Onion Router browser. Data collection occurred between October and November 2019.

Results
We identified 1929 listings from 201 unique sellers. The top product across the three markets were vape cartridges (range = 39.4% to 70.4%). The most common substance in these products was cannabis oil (range = 82.1% to 96.1%), followed by synthetic cannabinoids (range = 3.7% to 9.8%) and psychedelic substances (range = 0.2% to 6.4%). Vendors were primarily from the USA. Many products offered worldwide shipping (range = 42.4% to 96.3%).

Conclusions
Our study fills knowledge gaps by providing information on what vaping products are being sold through online cryptomarkets. Future studies should continue to monitor cryptomarkets to identify emerging trends of substances used in personal vaporisers.

Key messages
Online cryptomarkets provide a new way of monitoring emerging vaping trends and identify factors that contributes to the current vaping epidemic.
1467Interaction effects of multimorbidity and frailty on adverse health outcomes in elderly hospitalised patients
Authors: Lujic Sanja , Randall Deborah , Simpson Judy , Falster Michael , Jorm Louisa 
Published: September 2021

Abstract

Background
Multimorbidity and frailty are each known to be drivers of adverse outcomes, but their joint effects are less well known.

Methods
We used state-wide hospital and mortality data for persons aged ≥75 years, admitted during 2010-2012 in New South Wales, Australia, to ascertain multimorbidity, frailty risk and outcomes: prolonged length of stay (LOS), 30-day mortality and 30-day emergency readmission. We estimated the relative risk (RR) of each outcome using Poisson models with random intercept for hospital. Interactions on both additive and multiplicative scales were examined.

Results
Among 257,535 elderly inpatients, 33.6% had multimorbidity and elevated frailty risk, 14.7% had multimorbidity only, 19.9% had elevated frailty risk only and 31.8% had neither. Additive interactions were present for all outcomes, with a further multiplicative interaction for mortality and LOS. Mortality risk was 4.2 (95% CI 4.1 – 4.4), prolonged LOS 3.3 (95% CI 3.3 – 3.4) and readmission 1.8 (95% CI 1.7 – 1.9) times higher in patients with both factors present compared with patients with neither.

Conclusions
Multimorbidity and frailty coexist in older hospitalized patients and interact to increase the risk of adverse outcomes beyond the sum of their individual effects. Their joint effect should be considered in health outcomes research and when administering hospital resources.

Key messages
Multimorbidity and frailty coexist and interact to increase the risk of adverse outcomes in hospitalised patients. Research and health planners should consider their joint effects to ensure patients at the highest risk of adverse outcomes are identified.
801Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK biobank
Authors: Lumsden Amanda , Mulugeta Anwar , Zhou Ang , Hyppönen Elina 
Published: September 2021

Abstract

Background
The APOE gene has three main alleles; APOE-E2, E3 and E4 (global frequencies: 8%, 78%, 14%) carrying differential risk for conditions such as dementia and cardiovascular disease. Due to the clinical significance of variation at this locus, we explored disease associations of APOE genotypes using a hypothesis-free, phenome-wide association study (PheWAS) approach.

Methods
Utilising medical and genetic data available from the UK Biobank for 337,484 white British participants aged 37–73 years, we screened for associations between APOE genotypes (E4E4, E3E4, E2E4, E2E3 and E2E2) and ≥825 disease outcomes, using E3E3 as a reference.

Results
Case-control PheWAS analyses revealed associations with 37 disease outcomes from 17 distinct conditions after multiple test correction. As expected, E4E4 and E3E4 associated with risk of Alzheimer’s disease (p &lt; 10-46 for both), hypercholesterolemia (p &lt; 10-17), and cardiovascular diseases (p &lt; 10-4). Novel findings included E4-associated increased risk of chondrocalcinosis (E4E4), and protection against obesity (E4E4), type 2 diabetes (E4E4, E4E3), and chronic airway obstruction (E4E4; all p ≤ 3.2 × 10-4). Notably, E2E2 homozygosity augmented risks of peripheral vascular diseases, and cervical disorders (p ≤ 1·9 × 10-5).

Conclusions
PheWAS assessment of APOE-associated risk for a wide spectrum of diseases amongst this large, white British population, detected well-established, and novel APOE-disease associations warranting further validation.

Key messages
While APOE-E4 is risky for Alzheimer’s, and cardiovascular diseases, it may be protective against some metabolic conditions. While the E2 allele is often considered beneficial, homozygosity-associated risks may contribute to its relatively low prevalence.
692Association of drinking habits with TXNIP DNA methylation levels in leukocytes among general Japanese population
Authors: Maeda Keisuke , Yamada Hiroya , Munetsuna Eiji , Fujii Ryosuke , Yamazaki Mirai , Ando Yoshitaka , Mizuno Genki , Ishikawa Hiroaki , Ohashi Koji , Tsuboi Yoshiki , Hashimoto Shuji , Hamajima Nobuyuki , Suzuki Koji 
Published: September 2021

Abstract

Background
Thioredoxin-interacting protein (TXNIP) inhibits the activity of thioredoxin (TXN), leading to increased oxidative stress. Expression of the TXNIP gene is regulated by DNA methylation. However, no study has reported the influence of lifestyle factors on TXNIP DNA methylation. Our goal was to determine the association between drinking habits and TXNIP DNA methylation levels in the general Japanese population.

Methods
We conducted a cross-sectional study of 404 subjects (176 males and 228 females) participating in a health examination. Subjects were divided into non-, moderate (male: 1-39g; female: 1-19g ethanol/day) and heavy (male: ≥40g; female: ≥20g ethanol/day) drinkers based on self-reported drinking habits. We used a pyrosequencing assay to determine TXNIP DNA methylation levels in leukocytes.

Results
Among men, the mean TXNIP DNA methylation level in heavy drinkers (73.2%) was significantly lower than that in non- and moderate drinkers (non: 76.7%, p&lt;0.001; moderate: 75.8%, p=0.024). In multiple linear regression analysis adjusted for confounding factors, TXNIP DNA methylation levels showed significant negative association with alcohol consumption per day and cumulative alcohol consumption in male current drinkers.

Conclusions
We found that heavy drinkers had TXNIP DNA hypomethylation compared to non- and moderate drinkers in men. Moreover, alcohol consumptions were also negatively associated with TXNIP DNA methylation levels in male current drinkers.

Key messages
Heavy drinkers had decreased levels of TXNIP DNA methylation compared to non- and moderate drinkers in men.
680NSAID use and ovarian cancer survival
Authors: Majidi Azam , Na Renhua , Jordan Susan , Obermair Andreas , Webb Penelope M 
Published: September 2021

Abstract

Background
Observational studies have reported survival benefits associated with non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and non-aspirin NSAIDs (NA-NSAIDs), especially new use post-diagnosis, in women with ovarian cancer (OC).

Methods
Participants were women aged 18-79 diagnosed with OC in Australia, 2012-2015. Information was gathered through self-completed 3-monthly questionnaires and prescription records. Exposure was defined as any use (NA-NSAIDs/regular-dose aspirin □1/week or daily low-dose aspirin) during the year pre-diagnosis and first year post-diagnosis. We measured overall survival from start of primary treatment (surgery/neoadjuvant chemotherapy) (pre-diagnosis use) or from 12 months after the start of therapy (post-diagnosis) until the earliest of date of death/last follow-up/5 years. Cox proportional hazards regression was used to estimate survival. We also applied inverse-probability of treatment weighting (IPTW), which balances comparison groups regarding potential confounders.

Results
We observed improved survival associated with pre-diagnosis use of aspirin/NA-NSAIDs ≥4 days/week (frequent-users) compared to &lt; 1/week (hazard ratio [HR] =0.72, 95% confidence interval [CI]=0.54-0.97). The association was close to null for those who used medications 1-3 days/week. Similarly, we saw a 30-40% improvement in survival associated with post-diagnosis aspirin/NA-NSAID use, again driven by frequent users (HR = 0.61, 95%CI=0.42-0.88). Results were similar when we excluded pre-diagnosis users, restricted to women who received chemotherapy, or assessed cancer-specific and progression-free survival. Results from IPTW models were similar to adjusted models.

Conclusions
Our findings suggest aspirin/NA-NSAID use might improve survival in women with OC. Larger cohorts or, preferably, a randomised controlled trial could clarify these findings.

Key messages
Use of aspirin/NA-NSAIDs may improve OC survival.
889Association of maternal smoking during pregnancy and early-childhood with adult insomnia symptoms
Authors: Melaku Yohannes Adama , Appleton Sarah , Reynolds Amy , Gill Tiffany , Sweetman Alexander M , Micic Gorica , Stevens David J , Lack Leon , Adams Robert 
Published: September 2021

Abstract

Background
Evidence regarding the association between perinatal smoking and insomnia symptoms in adulthood is limited. Using the UK 1970 Birth Cohort Study, we determined the association of maternal smoking during pregnancy and early-childhood with insomnia symptoms at 42 years.

Methods
Participants were followed from birth (1970; N = 9020; male, 48%) and age 5 (1975; N = 8050; male, 47.9%) to 42 years (2012). Data on maternal smoking was collected at birth and age 5; difficulties initiating or maintaining sleep (DIMS) and DIMS plus daytime symptoms (tiredness, irritability, depression and nervousness) [DIMS plus] at age 42. We used a direct acyclic graph to select confounders. A log-binomial logistic regression, adjusted for confounders, was used to estimate the association. Missing data were imputed via multiple imputation.

Results
The prevalence of DIMS and DIMS plus was 32% and 25%, respectively. There was a 25% [odds ratio (OR)=1.25; 95% confidence interval (CI): 1.12-1.38)] and 23% [OR = 1.23; 95% CI: 1.09-1.38] increase in odds of DIMS and DIMS plus among participants whose mothers smoked during pregnancy compared to those whose mother did not. A 24% [OR = 1.24; 95% CI: 1.12-1.37] and 18% [OR = 1.18; 95% CI: 1.05-1.33] increase in odds of DIMS and DIMS plus respectively, was observed among participants who had smoking mothers at age 5. Intensity and duration of smoking had a dose-response relationship with insomnia symptoms.

Conclusions
Maternal smoking during pregnancy and early-childhood is associated with increased risk of adult insomnia symptoms.

Key messages
This study suggests that reducing maternal smoking may reduce the risk of adult insomnia.
68Maternal exposure to PM2.5 from a severe smoke event and birth outcomes in Victoria, Australia
Authors: Melody Shannon , Wills Karen , Ford Jane , Venn Alison , Johnston Fay 
Published: September 2021

Abstract

Background
The 2014 Hazelwood coal mine fire was an unprecedented six-week severe smoke event in the Latrobe Valley, southeastern Australia. We aimed to determine whether maternal exposure to fine particulate matter (PM2.5) attributable to the event was associated with adverse fetal growth or maturity, including birthweight, small for gestational age, term low birthweight or preterm birth.

Methods
A cohort of babies born within the affected region was defined used administrative perinatal data. Maternal average and peak PM2.5 was assigned to residential address at time of delivery using a chemical transport model. Maternal, infant, meteorological and temporal variables were included in final linear and log-binomial regression models.

Results
3,591 singleton livebirths were included; 763 were exposed in utero. Average PM2.5 exposure was 4.4 µg/m3 (IQR 2.1 µg/m3); average peak was 45.0 µg/m3 (IQR 35.1 µg/m3). No association between PM2.5 and fetal growth or maturity was observed. Gestational diabetes mellitus was an effect modifier in the relationship; babies of exposed gestational diabetic mothers were 97 grams heavier per 10 µg/m3 increase in average PM2.5 exposure (95%CI 74, 120 grams), compared to mothers without gestational diabetes.

Conclusions
Maternal PM2.5 exposure from a smoke event was not associated with adverse fetal growth or maturity. There was a trophic response amongst babies of mothers with gestational diabetes.

Key messages
Babies born to mothers with gestational diabetes may be more susceptible to the effects of smoke events on birthweight.
531Investigating systemic autoimmune diseases as a group of causes of death: mortality burden and comorbidities
Authors: Mitratza Marianna , Klijs Bart , Hak A Elisabeth , Kardaun Jan WPF , Kunst Anton E 
Published: September 2021

Abstract

Background
Systemic autoimmune diseases (SAIDs) have chronic trajectories and share characteristics of self-directed inflammation and aspects of clinical expression. Nonetheless, burden-of-disease studies rarely investigate them as a distinct category. This study aims to assess the mortality rate of SAIDs as a group and to evaluate co-occurring causes of death.

Methods
We used death certificate data in the Netherlands, 2013-2017, (N = 711,247) and constructed a SAIDs list (4-position ICD-10). The mortality rate of SAIDs as underlying Cause of Death (CoD), non-underlying CoD, and any-mention CoD was calculated. We estimated age-sex-standardized observed/expected ratios to assess comorbidities in deaths with SAID relative to the general deceased population.

Results
We observed 3,335 deaths with SAID on their death certificate (0.47% of all deaths). The mortality rate of SAID was 14.6 per million population as underlying CoD, 28.0 as non-underlying CoD, and 39.7 as any-mention CoD. The mortality rate was higher for females and increased exponentially with age. SAID-related deaths were positively associated with all comorbidities except for solid neoplasms and mental conditions. Particularly strong was the association with musculoskeletal (O/E=3.38,95% CI[2.98,3.82]), other genitourinary (O/E=2.73,95% CI[2.18,3.38]), blood (O/E=2.02,95% CI[1.70,2.39]), skin and subcutaneous tissue (O/E=1.95,95% CI[1.54,2.45]), and infectious diseases (O/E=1.85,95% CI[1.70,2.01]), as well as influenza (O/E=2.71,95% CI[1.74,4.03]).

Conclusions
Systemic autoimmune diseases constitute a rare group of causes of death, but contribute to mortality through multiple comorbidities. Classification systems could be adapted to better encompass these diseases as a category.

Key messages
Reclassification of readily available data provides useful estimates for the mortality burden of systemic autoimmune diseases in the population.
985Sex differences in the incidence of renal cell carcinoma: results from the EPIC cohort study
Authors: Muller David , Scelo Ghislaine , Riboli Elio 
Published: September 2021

Abstract

Background
Incidence of renal cell carcinoma (RCC) is two-fold higher in men compared with women. This ratio has been remarkably stable, both geographically and over time. We investigated whether established risk factors for RCC can explain the higher incidence in men.

Methods
230,399 participants in the EPIC cohort study with complete data for BMI, history of hypertension, and smoking variables were included. Cox regression models with age as the time-scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for sex.

Results
We identified 690 incident RCC cases. The marginal HR [95% CI] for men versus women was 2.30 [1.98, 2.69]. There was no strong evidence for interactions between hypertension, BMI, or smoking status and sex. Adjusting for BMI, hypertension and smoking variables did not materially affect the estimate (HR: 2.18 [1.85, 2.56]), accounting for only 10% of the observed excess risk. In contrast, smoking factors alone could account for 88% of the observed excess risk of lung cancer for men (marginal HR: 2.19 [2.02, 2.38]; adjusted HR: 1.14 [1.04, 1.25])

Conclusions
The two-fold higher incidence of RCC in men compared with women cannot be explained by established risk factors.

Key messages
Whilst obesity, hypertension, and smoking are established risk factors for RCC, they cannot account for the greater incidence among men compared with women. This indicates the presence of as yet unknown factors to which men are more susceptible than women.
990Seaweed intake and risk of cardiovascular disease: the Japan Public Health Center–based Prospective (JPHC) Study
Authors: Murai Utako , Yamagishi Kazumasa , Sata Mizuki , Kokubo Yoshihiro , Saito Isao , Yatsuya Hiroshi , Ishihara Junko , Inoue Manami , Sawada Norie , Iso Hiroyasu , Tsugane Shoichiro 
Published: September 2021

Abstract

Background
The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease (IHD) risk among a Japanese study population.

Methods
We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake in the study subjects was estimated from the food frequency questionnaire at baseline (1990–1994). Stroke and IHD events were identified until the end of 2009 (Cohort I) or 2012 (Cohort II). The hazard ratios (HRs) (95% confidence intervals [CIs]) for incident cardiovascular disease (CVD) and its subtype were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors by sex.

Results
During 1,493,232 person-years of follow-up, 4,777 strokes and 1,204 IHD cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption were seen in IHD (0.76 [0.58-0.99]; P-trend=0.04) compared to almost no seaweed consumption. Among women, such inverse associations were observed in incident IHD (0.56 [0.36-0.85]; P-trend=0.006). No significant associations were observed between seaweed intake and risk of stroke nor stroke subtypes among either men or women.

Conclusions
Seaweed intake has been shown to contribute to the prevention of IHD in a large Japanese cohort.

Key messages
Seaweed intake could be beneficial for prevention of IHD.
242Exploring health in the UK Biobank: cross-sectional analyses of sociodemographic, psychosocial, lifestyle and environmental factors
Authors: Mutz Julian , Roscoe Charlotte J , Lewis Cathryn M 
Published: September 2021

Abstract

Background
Our aim was to examine sociodemographic characteristics, psychosocial factors, lifestyle and environmental exposures associated with health.

Methods
The UK Biobank recruited &gt;500,000 participants, aged 37-73, between 2006-2010. Data on 81 cancer and 443 non-cancer illnesses were used to classify participants by insurance health status (non-standard risk/standard risk). Long-standing illness (yes/no) and self-rated health (poor/fair/good/excellent) constituted secondary outcomes. Logistic and ordinal regression models were fit to estimate associations between explanatory variables and health.

Results
307,378 participants (mean age=56.1; 51.9% female) were selected for cross-sectional analyses. Low household income, high levels of neighbourhood deprivation, being male, loneliness and social isolation were associated with poor health. Walking frequency and engaging in vigorous-intensity physical activity were associated with positive health, whereas long sleep duration, high body mass index and smoking were associated with poor health. Alcohol intake less frequent than 1-2 times per week was associated with poor health. There was some evidence that high levels of airborne pollutants (PM2.5, PM10 and NO2) and noise (Lden) were associated with poor health, although findings were inconsistent once other factors had been adjusted for. Neighbourhood greenspace was associated with positive self-rated health.

Conclusions
Public health could put greater focus on non-medical factors such as loneliness, further encourage healthy lifestyle behaviours and weight management, and examine efforts to improve health outcomes of individuals in the lowest income groups.

Key message
Multiple sociodemographic, psychosocial, lifestyle and environmental factors are associated with health.