bluuebunny/crossref_metadata_2025_split huggingface dataset:
521Performance of doubly-robust, machine learning effect estimators in realistic epidemiologic data settings and practical recommendations
Authors: Huang Jonathan , Meng Xiang 
Published: September 2021

Abstract

Background
Flexible, data-adaptive algorithms (machine learning; ML) for nuisance parameter estimation in epidemiologic causal inference have promising asymptotic properties for complex, high-dimensional data. However, recently proposed applications (e.g. targeted maximum likelihood estimation; TMLE) may produce biases parameter and standard error estimates in common real-world cohort settings. The relative performance of these novel estimators over simpler approaches in such settings is unclear.

Methods
We apply double-crossfit TMLE, augmented inverse probability weighting (AIPW), and standard IPW to simple simulations (5 covariates) and “real-world” data using covariate-structure-preserving (“plasmode”) simulations of 1,178 subjects and 331 covariates from a longitudinal birth cohort. We evaluate various data generating and estimation scenarios including: under- and over- (e.g. excess orthogonal covariates) identification, poor data support, near-instruments, and mis-specified biological interactions. We also track representative computation times.

Results
We replicate optimal performance of cross-fit, doubly robust estimators in simple data generating processes. However, in nearly every real world-based scenario, estimators fit with parametric learners outperform those that include non-parametric learners in terms of mean bias and confidence interval coverage. Even when correctly specified, estimators fit with non-parametric algorithms (xgboost, random forest) performed poorly (e.g. 24% bias, 57% coverage vs. 10% bias, 79% coverage for parametric fit), at times underperforming simple IPW.

Conclusions
In typical epidemiologic data sets, double-crossfit estimators fit with simple smooth, parametric learners may be the optimal solution, taking 2-5 times less computation time than flexible non-parametric models, while having equal or better performance. No approaches are optimal, and estimators should be compared on simulations close to the source data.

Key messages
In epidemiologic studies, use of flexible non-parametric algorithms for effect estimation should be strongly justified (i.e. high-dimensional covariates) and performed with care. Parametric learners may be a safer option with few drawbacks.
1455Leveraging multi-omic negative controls for effect estimation in molecular epidemiologic studies: A simulation study
Authors: Huang Jonathan 
Published: September 2021

Abstract

Background
Exploratory null-hypothesis significance testing (e.g. GWAS, EWAS) form the backbone of molecular epidemiology, however methods to identify true causal signals are underdeveloped. Via plasmode simulation, I evaluate two approaches to quantitatively control for shared unmeasured confounding and recover unbiased effects using complementary epigenomes and biologically-informed structural assumptions.

Methods
I adapt proposed negative control-based estimators, the control outcome calibration approach (COCA) and proximal g-computation (PG) to case studies in perinatal molecular epidemiology. COCA may be employed when maternal epigenome has no direct effects on phenotype and proxy shared unmeasured confounders and PG further with suitable genetic instruments (e.g. mQTLs). Baseline covariates were extracted from 777 mother-child pairs in a birth cohort with maternal blood and fetal cord DNA methylation array data. Treatment and outcome values were simulated in 2000 bootstraps. Bootstrapped, ordinary (COCA) and 2-stage (PG) least squares were fitted to estimate treatment effects and standard errors under various common settings of missing confounders (e.g. paternal data). Doubly-robust, machine learning estimators were explored.

Results
COCA and PG performed well in simplistic data generating processes. However, in real-world cohort simulations, COCA performed acceptably only in settings with strong proxy confounders, but otherwise poorly (median bias 610%; coverage 29%). PG performed slightly better. Alternatively, simple covariate adjustment for maternal methylation outperformed (median bias 22%; 71% coverage) COCA, PG, and machine learning estimators.

Discussion
Molecular epidemiology provides key opportunity to leverage biological knowledge against unmeasured confounding. Negative control calibration or adjustments may help under limited scenarios where assumptions are fulfilled, but should be tested with suitable simulations.

Key messages
Quantitative approaches for unmeasured confounding in molecular epidemiology are a critical gap. Negative control calibration or adjustment may help under limiting scenarios. Proposed estimators should be tested in simulation settings that closely mimic target data.
496Higher predicted 10-year risk for cardiovascular disease in primary care consulters for osteoarthritis
Authors: Huang Miss Xiaoyang , Yu Dahai , Wilkie Ross , Mamas Mamas 
Published: September 2021

Abstract

Background
Osteoarthritis (OA) has a major impact on the global burden of disease and is associated with poorer cardiovascular disease (CVD) outcomes. However it’s unclear whether people with OA have higher long-term (10-year) CVD risk compared to people without OA. This study uses electronic health record (EHR) data from a national representative database to calculate the Framingham-score (a gender-specific risk algorithm) to test the hypothesis that OA consulters have higher long-term CVD risk than non-OA consulters.

Methods
205,368 incident OA consulters with 1:1 age, gender, and practice-matched non-OA controls extracted from Clinical Practice Research Datalink (CPRD) were included. All predictors extracted from EHRs within three years prior to the index consultation were used to fit the Framingham-score. Absolute difference (AR) and relative rate ratio (RR) in the proportion of high-risk (predicted-risk ≥20%) individuals between OA and controls were estimated using Poisson regression.

Results
The proportion of high-risk individuals was higher in consulters for OA (5.69 (95% confidence interval (CI): 5.59-5.79)%) cf. 4.37 (4.28-4.46)%). The adjusted AR and RR was (1.94 (95%CI: 1.78-2.10) %) and (1.30 (1.27-1.34)), respectively.

Conclusions
This study confirms the expected higher predicted 10-year CVD risk in OA consulters compared to controls. This suggests that OA consulters could be a target group for more proactive interventions to prevent CVD events.

Key messages
OA consulters have a higher CVD risk predicted by Framingham-score calculated using EHRs than controls; OA consulters are a high risk group that can be considered as a target group for proactive prevention interventions for CVD.
910Maternal adversity and cardiovascular health of the offspring
Authors: Hyde Natalie , Scovelle Anna , Dowty James , Olive Lisa , O'Neil Adrienne 
Published: September 2021

Abstract

Background
We investigated the respective and cumulative impact of mothers’ exposure(s) to adversity over time on cardiovascular (CV) outcomes of her offspring.

Methods
Participants were part of the Avon Longitudinal Study of Parents and Children. Offspring CV measures were collected at seven and 17 years of age. Maternal adversity was self-reported from the onset of pregnancy to 8-weeks postnatal. Linear mixed models were used to analyse associations between adversity and log-transformed longitudinal CV outcomes.

Results
There was no association between cumulative or perceived impact of maternal adversity with CV outcomes in either sex. Specific adversities were associated with CV outcomes. For example, at age seven in girls, “Argued with partner” (β:0.9764 95%CI:0.9608-0.9922) was associated with decreased heart rate, and at age 17 “Partner rejected pregnancy” (β:1.0716 95% CI:1.0191-1.1269) with increased heart rate. In boys, at age seven “Partner was ill” (β:0.9713 95%CI:0.9511-0.9920) was associated with decreased systolic blood pressure, and at age 17 “Very ill” (β:1.0323 95%CI:1.0091-1.0561) with increased systolic blood pressure.

Conclusions
There were no associations evident with the primary exposure measure of maternal adversity and offspring CV outcomes. Specific adversities were associated with favourable changes in offspring CV outcomes at age seven, however the association reversed at age 17. This could be due to a protective adaptive response to maternal adversity present in childhood that may reverse trajectory by age 17.

Key messages
There was no association between cumulative maternal adversity and offspring cardiovascular outcomes, however specific events may be associated with cardiovascular outcomes in an age-dependent manner.
618Is mode of first birth a risk factor for subsequent preterm birth?
Authors: Gugusheff Jessica , Patterson Jillian , Torvaldsen Siranda , Ibiebele Ibinabo , Nippita Tanya 
Published: September 2021

Abstract

Background
Previous preterm birth is a strong predictor of subsequent preterm birth but less is known about the causes of preterm birth following a full-term pregnancy. Recent research highlighted previous caesarean as a potential risk factor and we aimed to further explore this risk.

Methods
This population-based record linkage study included all women in NSW, Australia who had a live singleton first birth at ≥ 37 weeks gestation, followed by a singleton second birth between 2005–2017. Relative risk (RR) and 95%CI of having a subsequent preterm birth, spontaneous preterm birth or preterm pre-labour caesarean was calculated using individual modified Poisson regression models, with mode of first birth as the exposure.

Results
Women who had an intrapartum (RR:1.26, 95%CI 1.19–1.32) or prelabour caesarean (RR:1.26,95%CI 1.18–1.35) first birth had a higher risk of subsequent preterm birth, than those who birthed vaginally. Those who had a pre-labour caesarean (RR:0.74, 95%CI 0.67–0.82) had a lower risk of subsequent spontaneous preterm birth. However, prior pre-labour caesarean also greatly increased the risk of subsequent preterm prelabour caesarean (RR:5.25, 95%CI 4.65–5.93).

Conclusions
Pre-labour and intrapartum caesareans have differing effects on the risk of subsequent spontaneous preterm birth and preterm pre-labour caesarean.

Key messages
The risk of subsequent preterm birth following a first birth caesarean depends on whether the caesarean occurred before or after the onset of labour and whether the subsequent preterm birth is spontaneous or a pre-labour caesarean.
1332Endometriosis, assisted reproductive technology and adverse pregnancy outcomes: a population based data linkage study
Authors: Ibiebele Ibinabo , Nippita Tanya , Baber Rodney , Torvaldsen Siranda 
Published: September 2021

Abstract

Background
Endometriosis is a chronic inflammatory disease characterised by endometrial tissue outside the uterus – pain and infertility are common symptoms. There is a paucity of data on the association between endometriosis and adverse pregnancy outcomes where the contribution of assisted reproductive technology (ART) use is also considered. This study will examine the association between endometriosis, with and without ART use, on adverse pregnancy outcomes.

Methods
Population data linkage study of all female NSW residents aged 15-45 years with a singleton birth in 2006-2015. Pregnancies were classified into 4 groups based on endometriosis diagnosis (yes/no) and ART use (yes/no). Multinomial logistic regression was used to estimate the odds of adverse pregnancy outcomes with 99% confidence intervals, adjusting for maternal and pregnancy factors. Outcomes assessed included placenta praevia, antepartum haemorrhage, planned birth (induction of labour or caesarean section) and preterm birth.

Results
Of 889,101 eligible pregnancies, women with endometriosis were more likely to be older while women who used ART were more likely to be nulliparous, birth in a private hospital and less likely to smoke. Adjusted odds ratios for selected study outcomes are outlined below.

Conclusions
Endometriosis is associated with increased odds of preterm birth, placenta praevia, antepartum haemorrhage and planned birth. In general, the odds of adverse pregnancy outcomes associated with endometriosis were further increased with ART use.

Key messages
These findings suggest that women with endometriosis, especially those who achieved pregnancy via ART use, represent a high risk obstetric population requiring appropriate surveillance and management.
552The lung function and airway inflammation markers associated with short-term pollen exposure- A systematic review
Authors: Idrose N. Sabrina , Lodge Caroline , Koplin Jennifer , Vicendese Don , Douglass Jo , Dharmage Shyamali 
Published: September 2021

Abstract

Background
Experimental challenge studies have shown that pollen can affect the lungs and airways. Here, we systematically reviewed community-based studies investigating outdoor pollen exposure, lung function and/or airway inflammation.

Methods
Four online databases were searched. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were studies published in English that were representative of the community. We only considered cross-sectional or short-term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was conducted using random-effects models.

Results
We included 27 of 6,551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type-2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta-analysis confirmed a positive relationship between pollen season and eosinophilic airway inflammation in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age.

Conclusion
Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type-2 airway inflammation rather than a non-specific or innate inflammation.

Key messages
This review indicates pollen exposure influences predominantly type-2 airway inflammation, but little evidence on lung function.
213Traditional Japanese Diet Score and healthy life expectancy - a longitudinal global study
Authors: Imai Tomoko , Sezaki Ayako , Miyamoto Keiko , Abe Chisato , Kawase Fumiya , Shirai Yoshiro , Inden Ayaka , Kato Takumi , Sanada Masako , Shimokata Hiroshi 
Published: September 2021

Abstract

Background
Traditional Japanese diets are considered to be health and longevity. We created a Traditional Japanese Diet Score (TJDS) and investigated the relationship between the TJDS and healthy life expectancy (HALE) longitudinally using global database.

Methods
Average food (g/day/capita) and energy supply (kcal/day/capita) by countries were identified by the Food and Agriculture Organization of the United Nations Statistics Division database. The sum of characterizing traditional Japanese foods supply (beneficial food components in Japanese diet; rice, fish, soybeans, vegetables, eggs, seaweeds, food components not use so much in Japanese diet; wheat, milk, and red meat) were divided as tertile (beneficial food components;-1, 0, 1, not use so much food components; 1, 0, -1). HALE values by country were derived from the Global Burden of Disease 2017 database. The longitudinal effects of TJDS on the rate of change in HALE from 1990 to 2013 were evaluated using a generalized mixed-effect model (GLMM), which takes into account the dependence of repeated observations within countries. The interaction between TJDS and survey year was applied to access the effects on HALE. This study covered 137 countries with populations of 1 million or greater.

Results
Longitudinal analysis controlled for covariates showed that smooth term of the interaction between TJDS and survey year was significant (p &lt; 0.001). The TJDS was negative associated with HALE in 1990, and in 1991, but positive associated after 2002.

Conclusions
The relationship between the TJDS as a healthy eating style and HALE is getting stronger since the 21st century.

Key messages
Well-balanced eating habits of traditional Japanese diets is supports healthy life expectancy.
1299Association between environmental cadmium exposure and plasma and urinary metabolite profiles in Japanese cohort study
Authors: Ishibashi Yoshiki , Harada Sei , Eitaki Yoko , Iida Miho , Kurihara Ayako , Hirata Aya , Shibuki Takuma , Okamura Tomonori , Hirayama Akiyoshi , Sugimoto Masahiro , Soga Tomoyoshi , Tomita Masaru , Takebayashi Toru 
Published: September 2021

Abstract

Background
The purpose of this study was to identify plasma and urinary metabolites that can be used to better identify the effects of cadmium exposure than N-acetyl-β-D-glucosaminidase (NAG) using capillary electrophoresis - mass spectrometry (CE-MS).

Methods
Urinary cadmium (U-Cd) was measured as an indicator of cadmium exposure. Fasting plasma and urine samples were collected from 1,412 men and 2,022 women in Tsuruoka Metabolomics Cohort Study. Charged 94 plasma and 123 urinary metabolites were detected and determined. Regression analysis was performed for urinary NAG, plasma, and urinary metabolites as dependent variables and U-Cd in quartiles as an independent variable. Multivariate regression model included age, SBP, smoke, rice intake, BMI, HbA1c, LDLc, alcohol consumption, physical activity, educational history, dietary energy intake, urinary Na/K ratio, and uric acid.

Results
The mean U-Cd of the population was 2.65 μg/g creatinine (SD: 1.63). NAG was positively associated with U-Cd, but the association was not significant with lower U-Cd quartiles. In the plasma metabolites, 10 metabolites had significantly negative association with U-Cd in all models and Cd quartiles. Among urinary metabolites, 27 metabolites had significantly positive association with U-Cd. Alanine was negatively associated with U-Cd in urinary metabolites. The trend test also showed significant dose-response trends for 9 plasma and all 28 urinary metabolites (p &lt; 0.05).

Conclusions
We found that the levels of Cd exposure, which did not cause an increase in NAG, caused changes in plasma and urinary metabolites.

Key messages
This study indicated that metabolomics might be promising and useful as markers of Cd exposure.
258Change in population mean BMI accounts for the majority of change in underweight and obesity
Authors: Iurilli Maria Laura Caminia 
Published: September 2021

Abstract

Background
Prevalence of underweight has decreased and that of obesity increased in most countries. A shift of the whole BMI distribution in the population would simultaneously change the mean BMI and the prevalence of underweight and obesity, whereas a change only at the tails would have limited impact on the mean.

Methods
Generalised linear regression of prevalence of underweight and obesity with mean BMI using worldwide data from 2,765 surveys with objectively measured height and weight on 143.5 million men and women aged 20 to 79 years from 1985 to 2016.

Results
Trends in the prevalence of underweight and obesity are largely driven by shifts in the distribution of mean BMI, with smaller contributions from changes in the shape of the distribution. There was a smaller than expected change in the decline of underweight in east and southeast Asia and sub-Saharan Africa and in the rise of obesity in Oceania.

Conclusions
The worldwide rise in obesity and decline in underweight are largely population phenomena. There is also evidence of excess obesity and persistent underweight beyond the distributional shift in some regions, which may be related to growing social inequalities that restrict access to healthy foods for those at highest risk of poor nutrition.

Key messages
Rise in obesity and decline of underweight are largely driven by increase in mean BMI. Effective response must include restrictions on unhealthy foods while making healthy options more accessible.
1536Antimicrobial resistance in the emerging COVID-19 pandemic
Authors: Jaiswal Abhishek , Jaiswal Ankita , Puri Surabhi , Pal Adarsh 
Published: September 2021

Abstract

Background
Inappropriate usage of antibiotics among COVID-19 patients can raise disastrous effects on antimicrobial resistance management and antibiotic stewardship programs. A study from USA reported 71% of COVID-19 patients received antibiotics while only 4% had bacterial co-infection. Similar findings were reported from a review of data from COVID-19 cases in Asia, which reported more than 70% of the patient receiving antibiotics however less than 10% on average had bacterial coinfection. The World Health Organisation discourages the use of antibiotics for mild cases of COVID-19, however they recommend it for severe cases at increased risk of secondary bacterial infection and death. This review aims to discuss the usage of antibiotics in COVID-19 patients pointing the role of bacterial coinfections, types of antibiotics used, and antibiotic resistance.

Methods
We systematically searched Medline, Cochrane library, Google Scholar for eligible studies published from 1st January 2020 till 29th May 2021. We included English language articles. We included patients of all age groups, in all settings. Primary outcome variable was bacterial coinfection and antimicrobial usage among COVID-19 patients.

Results
Less than 10% of the hospitalised COVID-19 patients had bacterial Co-infection. Antibiotics used among COVID-19 positives were moxifloxacin, ceftriaxone, azithromycin, piperacillin-tazobactam, levofloxacin, meropenem, etc.

Conclusions
Low proportion of COVID-19 patients had bacterial co-infection. Routine usage of antibiotics among COVID-19 positives should be discouraged.

Key messages
Bacterial co-infection among COVID-19 patients is low and therefore misuse of antibiotics among them should be discouraged.
1537Fighting against the pandemic or threatening the environment? Unforeseen challenges during COVID-19 pandemic
Authors: Jaiswal Abhishek , Shukla Nidhi , Singh Shashi Shekhar , Shrivastava Richa , Santra Archismita , Jaiswal Ankita , Salve Harshal 
Published: September 2021

Abstract

Background
In the current scenario of COVID-19 outbreak whereby the virus spreads through fomites and aerosols, there has been a huge increase in the use of soaps, sanitizers and personal protective equipment’s (PPEs) which in turn is causing huge amount of liquid and solid waste generation. We briefly describe here as how this pandemic is causing an impact on global environment. We also provide a rationale of using a modelled treatment framework using a reverse logistic network as temporary waste management measure during this pandemic.

Methods
We systematically searched Medline, Cochrane library, Google Scholar, Embase for articles published in English language describing the increased Biomedical waste generation in the current COVID-19 pandemic.

Results
As of July 2020, the volume of the COVID biomedical waste generated across India was 101 metric tons per day where Maharashtra was the largest producer of biomedical waste with about 17.5 metric tons per day.

Conclusions
Rationale use of personal protective equipment according to the exposure level of the biological hazard should be ensured by health workers and communities. Awareness regarding the proper disposal of the personal protective equipment and other biomedical wastes generated should be created. Also, proper segregation of biomedical wastes from the point of generation to the point of disposal and treatment should be done.

Key messages
Inappropriate usage and disposal of PPEs in the current COVID-19 pandemic is a huge hazard to the environment.