bluuebunny/crossref_metadata_2025_split huggingface dataset:
146Mendelian randomisation for mediation analysis: current methods and challenges for implementation
Authors: Carter Alice , Sanderson Eleanor , Hammerton Gemma , Richmond Rebecca , Smith George Davey , Heron Jon , Taylor Amy , Davies Neil , Howe Laura 
Published: September 2021

Abstract

Background
Mendelian randomisation uses genetic variants randomly allocated at conception as instrumental variables for an exposure. Methodological advances allow for mediation analysis to be carried out using Mendelian randomisation using either multivariable Mendelian randomisation or two-step Mendelian randomisation.

Methods
We use simulations and an applied example to demonstrate when multivariable Mendelian randomisation and two-step Mendelian randomisation methods are valid and how they relate to traditional phenotypic regression-based approaches to mediation. We demonstrate how Mendelian randomisation methods can relax assumptions required for causal inference in phenotypic mediation, as well as which Mendelian randomisation specific assumptions are required. We illustrate our methods in data from UK Biobank, estimating the role of body mass index mediating the association between education and cardiovascular outcomes.

Results
Both multivariable Mendelian randomization and two-step Mendelian randomization are unbiased when estimating the total effect, direct effect, indirect effect and proportion mediated when both confounding, and measurement error are present. Multivariable Mendelian Randomization can be used when multiple mediators are to be investigated in a single model.

Conclusions
Mendelian randomisation provides an opportunity to improve causal inference in mediation analysis. Although Mendelian randomisation specific assumptions apply, such as no weak instrument bias and no pleiotropic pathways, strong phenotypic assumptions of no confounding and no measurement error can be relaxed.

Key messages
Mendelian randomisation offers an opportunity to address bias by unmeasured confounding, measurement error and reverse causality in mediation analysis.
1243Quantitative risk-benefit assessment of fish and seafood consumption scenarios to support recommendations
Authors: Carvalho Catarina , Correia Daniela , Severo Milton , Afonso Cláudia , Bandarra Narcisa M. , Gonçalves Susana , Lourenço Helena M. , Graça Dias M. , Oliveira Luísa , Nabais Pedro , Carmona Paulo , Monteiro Sarogini , Borges Marta , Lopes Carla , Torres Duarte 
Published: September 2021

Abstract

Background
Fish/seafood consumption has health benefits, namely due to its omega-3 fatty acids levels and risks due to methylmercury contamination. This study aims to quantify the health impact of hypothetical scenarios of fish/seafood consumption through a risk-benefit assessment and provide support for recommendations, using Portuguese food consumption data.

Methods
We used data from the National Food, Nutrition and Physical Activity Survey 2015-2016 (n = 5811) to estimate the mean exposure to methylmercury and EPA+DHA in the current and alternative scenarios. Alternative scenarios were modelled using probabilistic approaches to reflect substitutions from the current consumption in the type of fish/seafood (predatory vs low-mercury species) or its frequency (1-7x/week). The overall scenarios’ impact was quantified using Disability-Adjusted Life Years (DALYs).

Results
About 14% of the Portuguese population exceeds the methylmercury tolerable weekly intake, and this prevalence is higher among small children (36.6%). Nevertheless, if the fish/seafood consumption increased to once a day, ≈11450 DALYs could be prevented each year. However, such a scenario would result in higher risk for pregnant women (1398 extra DALYs). Moreover, excluding predatory species consumption resulted in small but significant health gains (-1078 DALYs).

Conclusions
For the general population, the maximum health gains are obtained by consuming fish/seafood up to 7x/week, but among children and pregnant women, the frequency should be limited to 3-5x/week. All population should preferably choose non-predatory species.

Key messages
Daily fish consumption results in the highest overall populational health gain, but children and pregnant women need to limit it to 3-5x/week, due to methylmercury exposure.
1375Age-standardization to world population and under-estimation of oral cancer burden
Authors: Chaudhry Kishore , Bollu Prashanti 
Published: September 2021

Abstract

Background
Age-standardization is common for adjustment of unequal population in different ages as it can influence cancer incidence. However, for planning healthcare services (including screening), one needs absolute magnitude since everyone needs intervention. This study assessed the effect of age-standardization on understanding the global differentials in magnitude of oral cancer.

Methods
Data on cancer incidence rates of oral cancers for 2008-2012, was obtained from the website of international agency for research on cancer for all 334 population-based cancer registries. Scatter plots were prepared between age-standardized and crude incidence rates to assess the ratio between them according to proportion of old people for all countries. Areas with high occurrence of oral cancer were identified.

Results
The ratio between age-standardized and crude incidence rate was &gt;1 in countries with high proportion of older population (high-development-index countries), indicating an artificial widening of gap between incidence rates between countries due to age-standardization. Six areas had higher crude incidence rate among men than India. Based on the published estimates, the per-unit-population burden in Europe was 6.3% higher than India, while in USA it was merely 12.5% lower than India.

Conclusions
The perception of low burden of oral cancer in high-economy countries is artificial, brought about by common practice of age-standardization.

Key messages
Organization of oral cancer screening activities by countries with resources and expertise will provide much needed knowledge on its natural history and efficacy of control strategies.
1386Ethnic differences in lifestyle interventions for diabetes prevention: a systematic review and meta-analysis
Authors: Chen Mingling , Ukke Gebresilasea , Sood Surbhi , Bennett Christie , Khomami Mahnaz , Moran Lisa , Harrison Cheryce , Absetz Pilvikki , Teede Helena , Lim Siew 
Published: September 2021

Abstract

Background
The risk of type 2 diabetes varies by ethnicity, but ethnic differences in response to lifestyle interventions for diabetes prevention remain unclear. This systematic review and meta-analysis aimed to assess differences in the effects of lifestyle interventions on diabetes incidence, glycemic outcomes and anthropometric measures between ethnic groups.

Methods
MEDLINE, EMBASE, Pubmed, CINAHL, PsycInfo and EBM Reviews were searched (to June 2020) with no language restriction for randomized and non-randomized controlled trials on lifestyle interventions involving diet and/or physical activity in adults at risk of type 2 diabetes. Ethnicity was categorized into European, South Asian, Other Asian, Middle Eastern, Latin American and African groups based on the World Bank regions. Risk ratios for diabetes incidence and mean differences for glycemic outcomes (fasting glucose, 2-h glucose, HbA1c) and anthropometric measures (weight, BMI, waist circumference) were pooled using random-effects meta-analysis.

Results
Sixty articles representing 43 studies (18,691 participants) were included in meta-analyses. Overall, lifestyle interventions resulted in significant improvement in diabetes incidence, glycemic outcomes and anthropometric measures compared with controls (all P&lt;0.01). Significant subgroup differences by ethnicity were found for 2-h glucose, weight, BMI and waist circumference (all P&lt;0.05) but not for diabetes incidence, fasting glucose and HbA1c (all P&gt;0.05).

Conclusions
Lifestyle interventions are similarly effective in reducing diabetes incidence, fasting glucose and HbA1c for all ethnic groups, however, 2-h glucose and anthropometric outcomes should be optimized in certain ethnic groups.

Key messages
Lifestyle intervention is likely effective in preventing the progression to type 2 diabetes equally across all ethnic groups.
1235Household air pollution and lung cancer mortality among never-smokers: findings from the China Kadoorie Biobank
Authors: Cheng Elvin , Chan Ka Hung , Weber Marianne , Steinberg Julia , Canfell Karen , Yu Xue Qin 
Published: September 2021

Abstract

Background
Household air pollution (HAP) has been classified as a major risk factor for lung cancer (LC) among never-smokers, however, evidence is largely from case-control studies. Using the prospective cohort China Kadoorie Biobank (CKB), we investigated the association of HAP with LC death among never-smokers.

Methods
The CKB, a large-scale cohort study, recruited 512,715 adults aged 30–79 years from ten regions in China during 2004-2008. Self-reported never-smoking participants were followed up to 31/12/2016 with linkage to mortality data. Total duration of HAP exposure was calculated from self-reported solid fuel use in domestic cooking and slow-burning stoves in participants’ three most recent residences, and self-reported coal-smoky home in winter during their lifetime. Hazard ratios (HR) and 95% confidence intervals (CI) of LC death associated with HAP exposure were estimated using Cox regression, adjusting for key confounders including several demographic, environmental and lifestyle factors.

Results
There were 979 LC deaths among 323,794 never-smokers without prior cancer during a median follow-up of 10.2 years. There was a log-linear positive association between HAP exposure and LC death (p-trend=0.0034), with 4% increased risk per 5-year longer exposure (HR = 1.04; 95% CI 1.01-1.06); and participants with 40.1-50.0 years of exposure had the highest risk compared to the never-exposed (HR = 1.53; 95% CI 1.13-2.07).

Conclusions
This study provides new prospective evidence that HAP exposure is associated with LC death among Chinese never-smokers, and strengthens the previous evidence largely based on case-control studies.

Key messages
This study supports HAP as an important risk factor for LC development among never-smokers.
260Smoking, body mass index, and risk of vasomotor symptoms: a pooled analysis of eight studies
Authors: Chung Hsin-Fang , Anderson Debra , Mishra Gita 
Published: September 2021

Abstract

Background
Vasomotor symptoms (VMS), including hot flushes and night sweats, are linked with adverse health outcomes. This study investigated the associations between smoking, body mass index (BMI), and their joint effects with the risk of VMS.

Methods
We pooled individual-level data on 21,460 midlife women from eight cohort studies in the InterLACE consortium. Frequency or severity of VMS were self-reported and categorised into four levels (from none to frequent/severe). Multinomial logistic regression models were used to estimate relative risk ratios (RRRs) and 95%CIs adjusted for within-study correlation and covariates.

Results
Nearly 60% of the women experienced some degree of VMS; 30% were overweight, 21% obese, and 17% current smokers. We found that smoking more cigarettes with longer duration and earlier initiation and being overweight or obese were all associated with more frequent/severe VMS. Never smokers who were obese had a 1.5-fold increased risk of frequent/severe VMS (RRR 1.52, 95%CI 1.35-1.73), compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of frequent/severe VMS was much greater among smokers who were obese (RRR 3.02, 95%CI 2.41-3.78). However, women who quit smoking before age 40 years had a similar level of risk as never smokers.

Conclusions
Cigarette smoking and overweight/obesity substantially increased women’s risk of frequent or severe VMS in a dose-response manner, and smoking intensified the effect of obesity.

Key messages
Quitting smoking before age 40 years and maintaining a normal weight before the menopausal transition may mitigate the excess risk of VMS in midlife.
1517The effect of pregnancy on cardiovascular health in early adulthood: a difference in difference analysis
Authors: Clayton Gemma , Howe Laura , Parks Chloe , Leyland Kirsten , Hughes Alun , Fraser Abigail 
Published: September 2021

Abstract

Background
Pregnancy causes extreme cardiometabolic changes, yet evidence of its long-term cardiovascular effects is limited. Our aim was to estimate the causal effect of pregnancy on cardiovascular health.

Methods
We used a difference-in-difference (DiD) model to estimate the causal effect of pregnancy on multiple cardiovascular health measures (N = 445–1822 for cardiac echocardiography, blood based markers, blood pressure (BP) and anthropometry) in female participants in the Avon Longitudinal Study of Parents and Children with a pregnancy between 18-25 years. We differentiated between live birth and miscarriage/termination. Briefly, DiD assumes baseline differences in the outcome reflect confounding, that the rate of change in the outcome is similar in exposed and unexposed prior to the exposure, and that no new confounding was introduced after baseline. Any DiD at follow up is then attributed to the exposure.

Results
289 women had a pregnancy between ages 18-25 (15%). We found no effect of pregnancy on various echocardiography measures including left ventricular mass index. When accounting for changes in BMI, HDL-c and systolic BP at age 25 was -0.22mmol/L (95%CI:-0.28, -0.15) and -1.37mmHg (95%CI:-3.25, 0.52) lower, respectively, in women who had a live birth compared to no pregnancy. BMI, fat mass, and lean mass were higher in women who had a live birth versus no pregnancy.

Conclusions
Findings are consistent with limited existing evidence of BP lowering and lipid increasing effects of pregnancy. Future studies should investigate underlying mechanisms.

Key messages
Pregnancy results in a reduction in systolic BP and an adverse effect on HDL-c levels.
899Stepping up: identifying small-area variation in diabetes-related lower limb amputations
Authors: Cramb Doctor Susanna , Lazzarini Doctor Peter , Barnett Adrian , Daniel Mark 
Published: September 2021

Abstract

Background
Diabetes-related foot disease is the leading cause of lower limb amputations in Queensland. Amputations can be either minor (below the ankle joint) or major (above the ankle joint). Minor amputations may be performed to prevent major amputations prophylactically, but how these forms of amputations interrelate, and where their interrelationships are weakest and strongest, is unknown. Knowledge of small-area variation in interrelations between minor and major amputations is relevant to prevention and improved management of foot disease.

Methods
Data on lower limb amputations performed between 2014 and 2018 on patients aged 20+ years with diabetes were obtained from the Queensland Hospital Admitted Patient Data Collection. Rates were calculated using the number of people, rather than the number of amputation procedures. A Bayesian hierarchical spatial multivariate model was used to examine patterns over 516 populated statistical areas 2 in Queensland.

Results
During 2014 to 2018, 3,548 Queenslanders had at least one minor amputation, and 1,114 had at least one major amputation. Modelled amputation rates varied markedly across the State (standardised morbidity ratio (SMR) IQR: 0.67 to 1.22), with areas in far north Queensland having extremely high rates. There was consistently high area-level correlation between minor and major amputation rates. The highest SMRs for both minor and major amputations were in the Northern Peninsula.

Conclusions
Elevated rates of minor and major amputations in areas in Queensland, most noticeably the far north, indicate an urgent need for greater support for people with diabetes-related foot disease.

Key messages
Text: Large differences in minor and major amputation rates across Queensland indicate that certain regions require greater assistance in managing diabetes-related foot disease.
1489Hearing loss before and after COVID-19 pandemic
Authors: Daimaru Graduate student Kaori , Wagatsuma Yukiko 
Published: September 2021

Abstract

Background
Hearing loss is a major issue in public health. It is caused by infections, loud sounds, chronic diseases, and aging. COVID-19 pandemic occurred in 2020 dramatically changed people’s lifestyle. People stay at home, more frequently use online materials and communication, thus may use an earphone continuously. This study aimed to examine whether COVID-19 pandemic has an impact on hearing ability in Japan.

Methods
The persons who attended annual health check-ups in a regional examination center in 2019 were compared to those attended in 2020. The study participants were taken an informed written consent. Hearing loss was defined as hearing threshold of &gt; 30 dB at 1 kHz and 4 kHz in either ear with pure-tone air-conduction audiometry. The rates of hearing loss were compared with the adjustment of age and sex. Two-sided p value &lt;0.05 was considered statistically significant.

Results
Among 3351 participants in 2019, and 3762 participants in 2020, males were 57.5% and 56.2%, median age was 48.0 and 48.5 years, respectively. Overall rate of hearing loss was 13.7% and 16.2% in 2019 and 2020, respectively. After controlling with age and sex, the rate of hearing loss showed significant increase in 2020 (p &lt; 0.05). The increase was observed in both age groups of 18-49 and 50-70 years (p&lt;0.05).

Conclusions
This study showed the prevalence of hearing loss was increased across ages after COVID-19 pandemic.

Key messages
Hearing ability may have been affected by lifestyle changes due to COVID-19 pandemic.
1540Mental health of Australian women before and during the COVID-19 pandemic
Authors: Dawadi Shrinkhala , Meehan Edward , Boyle Jacqueline , Enticott Joanne , Lim Siew 
Published: September 2021

Abstract

Background
The COVID-19 pandemic is associated with increased psychological distress in Australia and globally. Few studies have examined distress in women, a group vulnerable to experiencing increased financial and child-care stressors during the pandemic. Such epidemiological benchmark data is essential for population monitoring, and can inform policy by highlighting groups at increased risk of mental health burdens.

Methods
Analysis of women aged 18-50 from a nationally representative survey collected in October 2020 (n = 1005) and the 2017-18 National Health Survey (n = 4267). Trends in the prevalence of very high scores on the Kessler-10, a measure of psychological distress capturing symptoms of affective and anxiety disorders, were compared across the surveys and by sociodemographic characteristics (age, education, socioeconomic status, income, family type and employment change).

Results
Rates of very high psychological distress were 4.6% in 2017-18 (95% CI = 3.8%-5.4%) to 19.3% in 2020 (95% CI = 16.9%-21.8%), and were greater in 2020 across all sociodemographic subgroups. In 2020, rates were highest in women who experienced employment change (29.8%, 95% CI = 24.1%-35.6%), earned $0-$49,000 annually (25.7, 95% CI = 18.5%-32.9%), and were single with children (24.8%, 95% CI = 16.3%-33.2%).

Conclusions
Psychological distress has increased in Australian women during the pandemic, especially for those experiencing employment change, with lower incomes, or who are single parents. Findings will be discussed in the conjunction with extant social policies and access to mental health support.

Key messages
The rate of very high psychological distress has increased fourfold in Australian women during the pandemic.
1265Association between fruit and vegetable intake and depressive symptoms over 15 years in young women
Authors: Dharmayani Putu Novi Arfirsta , Mihrshahi Seema , Mishra Gita 
Published: September 2021

Abstract

Background
The role of higher intake of fruit and vegetables has been of particular interest as a novel approach to reduce the risk of depressive symptoms. This study examined the association between fruit and vegetable intake and depressive symptoms in the 1973-78 cohort in the Australian Longitudinal Study on Women’s Health.

Methods
A total of 4241 women with a mean age of 27.6 (SD 1.5) years were followed up at five surveys over 15 years starting from 2003. The Center for Epidemiologic Studies Depression-10 scale with a cut off &gt; 10 indicated depressive symptoms. Fruit and vegetable intake was assessed using short questions. Multiple imputations with generalised estimating equations models were performed to estimate odds ratio of depressive symptoms according to fruit and vegetable intake.

Results
Fruit and vegetables were cross-sectionally associated with reduced odds of depressive symptoms. In longitudinal analysis, higher intake of fruit (&gt; 4 servings) and vegetable (&gt; 5 servings) was consistently associated with a reduced odds of depressive symptoms, with a 25% reduced odds (OR 0.75; 95% CI 0.57, 0.98, p = 0.032) and a 19% reduced odds (OR 0.81; 95% CI 0.70, 0.94, p = 0.008) respectively.

Conclusions
These findings suggest that a higher intake of fruit and vegetables was associated with a lower risk of depression symptoms over 15 years from a population-based prospective study of Australian women.

Key messages
Increasing intake of fruit and vegetables in the younger population may be a promising approach to reducing the risk of depressive symptoms in the long run.
489Trends in method-specific suicide among Japanese adolescents in the past four decades
Authors: Dhungel Bibha , Thapa Anushka , Martinez-rives Noelia Lucia , Martin Pilar , Wada Koji , Gilmour Stuart 
Published: September 2021

Abstract

Background
In 2018 the overall suicide rate increased by 33% among students, as a part of a continued trend of rising suicide among adolescents. In 2015, the government of Japan aimed to reduce the overall suicide rate to 13 per 100,000 or less by 2025, but deaths among adolescents have been rising. This study analysed the trends in method-specific suicide among Japanese adolescents from 1979 to 2016 and compared suicide mortality rate in Japan with other OECD countries.

Methods
We obtained vital statistics data from the Japanese Ministry of Health, Labour and Welfare as well as the global health observatory of the WHO. Poisson regression analysis was performed separately by sex with year, age category, suicide method and a 1998 step variable as covariates.

Results
We found that hanging suicide rates among high school level boys are 12.15 times and girls are 6.17 times the rate of elementary school-aged children. The year 1998 saw a peak in suicide rates by hanging, which increased by more than 60% among both boys and girls. Japan is near the median of OECD suicide rates, with crude suicide mortality rates of 7.8 per 100,000 among 15–19-year-olds in 2016.

Conclusions
Suicide among adolescents has been rising during the last decades. Several factors related to the school and family environment, and mental health problems may have affected the adolescent suicide rate in Japan

Key messages
An urgent need is evident to address suicide among high school and university-aged adolescents.