bluuebunny/crossref_metadata_2025 huggingface dataset:
1036Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
Authors: Steinberg Julia , Lee Jin Yee , Wang Harry , Law Matthew , Smit Amelia , Nguyen-Dumont Tu , Giles Graham , Southey Melissa , Milne Roger , Mann Graham , MacInnis Robert , Cust Anne
Published: September 2021

Background

To improve melanoma early detection, tools to predict personal risk based on genetic information (polygenic risk scores, PRS) have been developed, but require external validation.

Methods

We analysed invasive melanoma incidence in UK Biobank (UKB; n = 395,647; 1,651 cases) and the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4,765; 303 cases). Three PRS were evaluated: 68 genetic variants (SNPs) at 54 loci from a 2020 meta-analysis (PRS68); 50 SNPs significant in the 2020 meta-analysis excluding UKB (PRS50); 45 SNPs at 21 loci known pre-2020 (PRS45). 10-year melanoma risks were calculated from population-level cancer registry data by age group and sex, with and without PRS adjustment.

Results

All PRS were strongly associated with melanoma incidence, including after adjustment for age, sex, ethnicity, and ease of tanning. Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in UKB (ratio expected/observed cases E/O=0.65, 95% confidence interval 0.62-0.68) and MCCS (E/O=0.65, 0.57-0.73). For UKB, this was reduced by PRS-adjustment, e.g. PRS50-adjusted risks E/O=0.91 (0.87-0.95). Discriminative ability for PRS68- and PRS50-adjusted absolute risks was higher than for risks based on age and sex alone (deltaAUC 0.07-0.1, p < 0.0001), and higher than for PRS45-adjusted risks (deltaAUC 0.02-0.04, p < 0.001).

Conclusions

A PRS derived from a larger, more diverse meta-analysis improves melanoma risk prediction compared to an earlier PRS. Re-calibration of absolute risks may be necessary for application to specific populations.

Key messages

A genetic score can improve prediction of melanoma risk and might help tailor melanoma prevention and early detection strategies to different risk levels.
674The incidence and risk factors of acute infectious diarrhea at Japanese geriatric intermediate care facilities
Authors: Suita Asae , Ohfuji Satoko , Fukushima Wakaba , Ito Kazuya , Kase Tetsuo , Kondo Kyoko , Ishibashi Motoki , Kumashiro Hiroko , Deguchi Akifumi , Nakata Hiroyuki , Kawai Shuji , Iba Kazuko , Kita Tetsuya , Kinugawa Kazuhiko , Sowa Etsuji , Nakazawa Hideo , Hamada Kazutaka , Fujimoto Mikio , Furukawa Yoshio , Hirota Yoshio
Published: September 2021

Background

Norovirus infection and Clostridioides difficile infection (CDI) are major causes of acute infectious diarrhea at medical facilities. “Geriatric intermediate care facilities” are a type of medical facility that tend to the daily life needs of elderly Japanese people. However, there is no research about norovirus- or CDI-related diarrhea at Japanese geriatric intermediate care facilities.

Methods

This prospective cohort study included 1445 residents at 10 geriatric intermediate care facilities in Osaka between November 2018 and October 2019. The study subjects were followed regarding the occurrence of acute infectious diarrhea and the results of rapid diagnostic tests for norovirus and CDI. We calculated incidence rates and hazard ratios (HR) with 95% confidential intervals (CI) to identify the risk factors of infectious diarrhea.

Results

Thirty-seven residents developed diarrhea during the observation period, although none of them was positive for norovirus or CDI. The total incidence rate was 1.21/10,000 person-days (95%CI: 0.82-1.60). Compared with residents aged 87-91 years, those aged ≤ 80 years had a significantly higher risk of diarrhea (HR = 3.85, 95%CI: 1.27-11.66). Moreover, residents with thyroid diseases had a significantly higher risk of diarrhea than those without thyroid disease (HR = 5.33, 95%CI: 2.32-12.25).

Conclusions

The incidence of acute infectious diarrhea is relatively low. However, residents who are < 80 years old and those with thyroid diseases are more likely to develop diarrhea.

Key messages

We describe the situation of acute infectious diarrhea at Japanese geriatric intermediate care facilities
925Ethnic differences and determinants of vitamin D deficiency in the UK Biobank
Authors: Sutherland Joshua , Zhou Ang , Leach Matthew , Hyppönen Elina
Published: September 2021

Background

While controversy remains regarding optimal vitamin D status, the public health relevance of true vitamin D deficiency is undisputed. There are few contemporary cross-ethnic studies investigating the prevalence and determinants of very low 25-hydroxyvitamin D [25(OH)D] concentrations.

Methods

We used data from 440,581 UK Biobank participants, of which 415,903 identified as white European, 7,880 Asian, 7,602 black African, 1,383 Chinese, and 6,473 of mixed ancestry. 25(OH)D concentrations were measured by DiaSorin Liaison XL and deficiency defined as ≤ 25 nmol/L 25(OH)D.

Results

The prevalence of 25(OH)D deficiency was highest among participants of Asian ancestry (57.2% in winter/spring and 50.8% in summer/autumn; followed by black African [38.47%/30.78%], mixed ancestry [36.53%/22.48%], Chinese [33.12%/20.68%] and white European [17.45%/5.90%], P < 1.0E-300). Participants with higher socioeconomic deprivation were more likely to have 25(OH)D deficiency compared to less deprived (P < 1.0E-300 for all comparisons), with the pattern being more apparent among those of white European ancestry and in summer (Pinteraction<6.4E-5 for both). In fully-adjusted analyses, regular consumption of oily fish was effective in mitigating ≤25 nmol/L 25(OH)D deficiency across all ethnicities, whilst outdoor-summer time was less effective for black Africans than white Europeans (OR: 0.89; 95% CI: 0.70, 1.12 and OR: 0.40; 95% CI: 0.38, 0.42, respectively).

Conclusions

Vitamin D deficiency remains an issue throughout the UK, particularly in lower socioeconomic areas and the UK Asian population, half of whom have vitamin D deficiency across seasons.

Key messages

The prevalence of 25(OH)D deficiency in the UK is alarming, with certain ethnic and socioeconomic groups considered particularly vulnerable.
1379Has the reporting quality of published randomised controlled trial protocols improved since the SPIRIT statement?
Authors: Tan Aidan , Tan Zet , Li Tom , Harris Ian , Naylor Justine , Siebelt Michiel , Tiel Jasper van , Pinheiro Marina , Harris Laura , Chamberlain Kira , Adie Sam
Published: September 2021

Background

The impact of the SPIRIT statement on the reporting quality of RCT protocols in health research is unknown. This methodological study aimed to determine the reporting quality of published randomised controlled trial (RCT) protocols before and after the SPIRIT statement, and any association with author, trial or journal factors.

Methods

RCT protocols were identified by searching MEDLINE, Embase and CENTRAL, included if published in full-text, English language and a peer-reviewed journal, and assessed with the SPIRIT statement checklist items.

Results

300 RCT protocols were retrieved; 150 from the period immediately before the SPIRIT statement and 150 from a recent period after the SPIRIT statement. 47.9% (95% CI, 46.5% to 49.3%) of checklist items were adequately reported in RCT protocols before the SPIRIT statement and 56.7% (95% CI, 54.9% to 58.5%) after the SPIRIT statement. This represents an 8.8% (95% CI, 6.6% to 11.1%; p < 0.0001) mean improvement in the overall proportion of checklist items adequately reported since the SPIRIT statement. The factors associated with higher reporting quality of RCT protocols in multiple regression analysis were author expertise or experience in epidemiology or statistics, multicentre trials, longer protocol word length and publicly reported journal policy of compliance with the SPIRIT statement.

Conclusions

The overall reporting quality of RCT protocols has significantly improved since the SPIRIT statement, although a substantial proportion of individual checklist items remain poorly reported.

Key messages

Continued, concerted and coordinated efforts are required by journals, editors, reviewers and investigators to improve the completeness and transparency of RCT protocols.
920Stakeholder analysis to develop a national outbreak response plan for Q fever in Australia
Authors: Tan Tabita , Heller Jane
Published: September 2021

Background

Q fever is a zoonotic disease that can cause prolonged and debilitating illness in humans. Australia has the highest number of cases reported in the world and animal-human outbreaks would require a coordinated response from both animal and public health authorities.

Methods

Expert opinion workshops are conducted across several states in Australia. Discussions were audio recorded and transcribed for thematic analysis to elicit sources and routes of transmission that would lead to a large human outbreak, risk factors for outbreaks and variations between states.

Results

Sources of Q fever for human infection differ between jurisdictions, influenced by disease occurrence and case infection source. Risk factors include aggregation of animals, environmental effects and naïve human contact. Community acquired infection is perceived as a greater outbreak risk than occupationally acquired due to lack of awareness, absence of vaccination and increased exposure of the public.

Conclusions

Disease occurrence and sources of infection are variable across jurisdictions and a generalised outbreak plan is not the solution. The framework for action must reflect differences identified between jurisdictions.

Key messages

Expert opinion regarding sources and routes of transmission for a large human Q fever outbreak highlights prevailing differences between jurisdictions, for which a one size fits all outbreak response plan will not be effective.
1453Mapping the prevalence of chronic noncommunicable diseases in Ethiopia: a systematic review and meta-analysis of evidence
Authors: Tesfay Fisaha , Zorbas Christina , Alston Laura , Backholer Kathryn , Bowe Steven J. , Bennett Catherine M
Published: September 2021

Background

Noncommunicable diseases (NCDs) are a growing global health challenge disproportionately impacting low- and middle-income settings, including Ethiopia. Currently, the body of evidence describing the burden of NCDs is fragmented, inconsistent, health facility- or institution-based, and out-dated in Ethiopia. We conducted a systematic review of the literature and meta-analysis of the prevalence of NCDs in community settings in Ethiopia.

Review methodology

Community-based quantitative studies published in English between 2012 and July 2020 that reported the prevalence of NCDs in Ethiopia were included. A systematic search of Medline, Embase, Scopus, CINHAL, and Global Health using pretested search terms related to NCDs was conducted, and data were extracted using a piloted data extraction proforma adapted from the Joanna Briggs Institute tool. Meta-analysis was performed using Stata 16. We measured the overall NCD prevalence using pooled odds ratios with 95% CIs. Pooled NCD prevalence was also computed and presented using forest plots. I2 was used to assess heterogeneity. Studies that did not fulfil the criteria for meta-analysis were narratively synthesised.

Results

Nineteen studies met the inclusion criteria. Four studies measured the prevalence of NCDs (all NCDs together), ranging from 29% to 35% (prevalence estimates not pooled). The pooled prevalence of Diabetes Mellites (DM) across ten studies was 5% (95% CI:4%−7%). Three studies each reported on the prevalence of undiagnosed DM (pooled prevalence 8%, 95% CI: 2%−14%) and pre-DM (pooled prevalence 12%, 95% CI:3%−21%). In a narrative analysis the prevalence of cardiovascular conditions ranged from 13.4% to 32.2% (n = 3 studies), cancer mortality ranged from 4% to 18% (n = 3 studies) and respiratory conditions ranged from 1% to 18% (n = 3 studies).

Conclusion and recommendations

Our analysis found that approximately one-third of Ethiopians have an NCD, with cardiovascular diseases the most common of all NCDs. The prevalence of respiratory conditions also appears high, but there are insufficient data for a pooled estimate. Whilst the prevalence of DM appears relatively low, there is evidence that the magnitude is increasing. Public health actions to address the high burden of cardiovascular and respiratory diseases, as well as the increasing magnitude of DM in Ethiopia, must be prioritised.

Keywords: NCD, noncommunicable diseases, Ethiopia.
325The incidence of primary postpartum haemorrhage following in-hospital birth: a systematic review and meta-analysis
Authors: Tiruneh Bewket Tadesse , McLelland Gayle , Plummer Virginia
Published: September 2021

Background

Although primary postpartum haemorrhage is a leading cause of maternal mortality, in the wider literature, there is inconsistent results in studies about its incidence. This study was designed to determine the pooled incidence of primary postpartum haemorrhage among women following in-hospital births.

Methods

This review used a systematic review and meta-analysis approach. We systematically searched electronic databases of Ovid MEDLINE, Ovid Emcare, Embase, PsycINFO, and CINAHL. Studies reporting the incidence of primary postpartum haemorrhage following in-hospital births were included. The pooled incidence of primary postpartum haemorrhage with a 95% confidence interval was calculated using random-effects model. Heterogeneity test between studies, and publication bias were assessed with I-square statistics and Egger’s test respectively.

Results

Ten of the 1548 studies were found to be eligible and were included in this systematic review and meta-analysis. The pooled incidence of primary postpartum haemorrhage following in-hospital births was nearly 12% (95% CI: 7.74- 17.61), with no evidence of between studies heterogeneity.

Conclusions

The incidence of primary postpartum haemorrhage following in-hospital births was high, and suggest that preventive strategies implemented to reduce its occurrence needs further strengthening using training.

Key messages

The result of this review suggests that globally at least one in ten women experience a primary postpartum haemorrhage following in-hospital births. This is higher than anticipated. The application of the recommended strategies for the prevention of primary postpartum haemorrhage should be re-emphasized.
1221Baseline Global DNA Hypermethylation Increase the Risk of Cerebrovascular Disease Mortality in Japanese Population
Authors: Tsuboi Yoshiki , Yamada Hiroya , Munetsuna Eiji , Fujii Ryosuke , Yamazaki Mirai , Ando Yoshitaka , Mizuno Genki , Ishikawa Hiroaki , Ohashi Koji , Maeda Keisuke , Hashimoto Shuji , Hamajima Nobuyuki , Suzuki Koji
Published: September 2021

Background

DNA methylation plays an important role in progression of cardiovascular disease (CVD). The methylation status of long interspersed nuclear element-1 (LINE-1) reflects the global DNA methylation level and is associated with lipid profiles and glycemia. We conducted a longitudinal study to examine the association between LINE-1 DNA methylation and CVD mortality in a Japanese elderly population.

Methods

We targeted for 357 subjects (143 men and 214 women) who were more than 60 years, participated in the health checkup in 1990, and had no clinical history of cancer, stroke, or ischemic heart disease. During 29 years of follow-up period, total 69 subjects were died from CVD, and died of cerebrovascular disease (CBD) and ischemic heart disease (IHD) were 25 and 13, respectively. LINE-1 DNA methylation was measured using PBMCs. We defined the hypermethylation group as greater than median of the LINE-1 DNA methylation levels and hypomethylation group as others. Multivariable Hazard ratios (HRs) for each disease mortality were calculated by the Cox proportional hazard model. We adjusted for age, sex, smoking habits, and alcohol consumption.

Results

Significantly higher HRs for CVD and CBD mortality were observed in the hypermethylation group compared to the hypomethylation group (CVD: HR 1.67 [95%CI 1.02-2.73], CBD: HR 3.29 [95%CI 1.29-8.40]). However, IHD mortality did not associated with LINE-1 DNA methylation.

Conclusions

We found that LINE-1 DNA hypermethylation in PBMCs was associated with high CVD mortality, especially CBD mortality.

Key messages

Higher levels of LINE-1 methylation in PBMCs can be a predictive marker for CBD risk
1471Metadata on calprotectin, an emerging biomarker of interest in COVID-19
Authors: Udeh Raphael
Published: September 2021

Background

COVID-19 has been shown to present with a varied clinical course, hence the need for more specific diagnostic tools that could identify severe cases and predict outcomes during COVID-19 infection. Recent evidence has shown an expanded potential role for calprotectin, both as a diagnostic tool and as a stratifying tool in COVID-19 patients in terms of severity. Therefore, this systematic review and meta-analysis aims to evaluate the levels of calprotectin in severe and non-severe COVID-19 and also identify the implication of raised calprotectin levels.

Methods

Databases searched include MEDLINE, EMBASE, the Cochrane Library, Web of Science, and MedRxiv. Stata was employed in meta-analysis to compare the serum/faecal levels of calprotectin between severe and non-severe COVID-19 infections.

Results

A pooled analysis of data in the 8 quantitative studies from 613 patients who were RT-PCR positive for COVID-19 (average age = 55 years; 52% males) showed an overall estimate as 1.34 (95%CI: 0.77, 1.91). Stata was further employed to carry out an in-depth investigation of the in-between study heterogeneity.

Conclusion

In conclusion, calprotectin levels have been demonstrated to be significantly elevated in COVID-19 patients who develop the severe form of the disease, and it also has prognostic significance.

Key message

This is the first comprehensive metadata on calprotectin in COVID-19. And as a druggable target for tasquinimod, calprotectin potentially remains a key therapeutic intervention strategy in COVID-19 management.
518Trajectories of offending in people with psychotic illness and other mental disorders: a population study
Authors: Valuri Giulietta , Morgan Adjunct Frank , Ferrante Anna , Jablensky Emeritus Assen , Morgan Winthrop Vera
Published: September 2021

Background

Trajectory analysis has been used to study long-term patterns of offending and identify offending groups. Only few studies have explored patterns in people with psychotic illness and these were restricted to adult offenders. This study examines offending trajectories, and identifies risk factors, for people aged 10-26 with psychotic illness (PI) and other mental disorders (OMD) compared to those with no mental disorders (NMD).

Methods

This is a whole-population record-linkage study of 184,147 people born in Western Australia (WA) 1983-1991 using data from WA psychiatric case register, WA corrective services and other state-wide registers. Group-based trajectory modelling was used to identify offending trajectories.

Results

Four offender groups were identified for each mental health status (MHS) group:

MHS groups had similar offending patterns, however PI had a lower proportion of individuals in the G1 group and later offending onset in the G3 group. Gender, indigenous status, substance use, childhood victimisation and parental offending were risk factors associated with group membership; for PI, childhood victimisation and parental offending were only significant in the G4 group.

Conclusions

Overall offending patterns and risk factors were similar for all MHS groups, however, some differences were observed for PI.

Key messages

To reduce offending in this population, interventions need to occur at an early age.
1343A systematic review and meta-analysis of tobacco smoking behaviour changes during the COVID-19 pandemic
Authors: Vaneckova Pavla , Sarich Peter , Cabasag Citadel Jungco , Liebermann Erica , Carle Chelsea , Hughes Suzanne , Egger Sam , O'Connell Dianne , Weber Marianne , da Costa Allini Mafra , Caruana Michael , Gouda Hebe , Canfell Karen , Ginsburg Ophira , Steinberg Julia , Soerjomataram Isabelle
Published: September 2021

Background

Globally, tobacco smoking remains the largest cause of premature death. The COVID-19 pandemic has forced nations to take unprecedented measures including ‘lockdowns’ that might impact tobacco smoking behaviour. We performed a systematic review and meta-analyses to assess smoking behaviour changes during the early phases of the COVID-19 pandemic.

Methods

We searched Medline/Embase/PsycINFO/BioRxiv/MedRxiv/SSRN databases (January-November 2020) for published and pre-print articles that reported specific smoking behaviour changes or intentions after the onset of the COVID-19 pandemic. We used random-effects models to pool prevalence ratios comparing the prevalence of smokers during and before the pandemic, and the prevalence of smoking behaviour changes.

Results

33 studies were included in meta-analyses, with smoking data for ∼230,000 participants across 24 countries. The proportions of smokers during and before the pandemic were similar, with a pooled prevalence ratio 0.85 (95%CI:0.76-0.95). In studies limited to smokers, 27% (95%CI:21-32%) smoked more, 17% (95%CI:13-21%) smoked less, 54% (95%CI:47-61%) smoked the same and 5% (95%CI:2-9%) reported quitting smoking. Among all participants, 1% (95%CI:0-2%) started smoking during the pandemic. All studies were at high risk of bias due to use of non-representative samples, likely non-response bias, and utilisation of non-validated questions.

Conclusions

Smoking behaviour changes during the early phases of the COVID-19 pandemic were highly mixed. Meta-analyses indicated slightly lower overall smoking prevalence during the pandemic, but higher intensity among smokers.

Key messages

More recent and higher quality studies of smoking behaviour changes are required to measure the longer term impact of the COVID-19 pandemic.
999Impact of Heatwaves on use of health services (GP and Emergency department visits)
Authors: Varghese Blesson , Beaty Matt , Bi Peng , Nairn John
Published: September 2021

Background

Heatwaves are associated with increases in mortality and morbidity (mostly hospitalisations). However, evidence regarding heatwave impacts on the use of frontline health-services such as general practitioner (GP) consultations and emergency department (ED) services is limited. This study quantified the impact of heatwaves on the use of GP and ED services in Adelaide.

Methods

Data on GP services (2011-2016) from the Medicare Benefits Schedule and ED visits (2013-2018) were obtained from the Australian Bureau of Statistics and the Department of Health, respectively. Heatwaves were defined using Excess Heat Factor. Using time-stratified case-crossover models, we modelled heatwave-severity (low, severe/extreme) against the use of GP and ED services in the warm-season (October-March). Effect estimates are reported as relative risks (RRs).

Results

Total GP visits decreased during low-intensity heatwaves and increased during severe/extreme heatwaves (RR 1.14; 95%CI: 1.13-1.15). The highest increases during severe/extreme heatwaves were observed for respiratory (RR 1.36; 95%CI: 1.27-1.45) and psychiatric services. While ED visits decreased overall during low-intensity and severe/extreme heatwaves, those due to heat-light disorders (RR 4.23; 95%CI: 2.98-6.00), volume depletion, and respiratory diseases increased during severe/extreme heatwaves.

Conclusions

There were significant increases in the use of GP and specific ED services during heatwaves in Adelaide. Further research is needed to identify the intrinsic and extrinsic vulnerability factors contributing to these increases in Adelaide and other Australian cities.

Key messages

Impacts of heatwaves extend beyond mortality to include frontline health-services (GP/EDs) that are already challenged. Evidence presented may assist policymakers for resource allocation and healthcare workforce capacity building.
1387Effect of yoga therapy on health of women with polycystic ovary syndrome: systematic-review and meta-analysis
Authors: Verma Anita , Upadhyay Vikas , Saxena Vartika
Published: September 2021

Background

The purpose of this study was to assess the effect of yoga therapy (YT) on health outcomes of women suffering from polycystic ovary syndrome (PCOS). Interventional studies, with postmenarchal and premenopausal females with PCOS who received YT, with any health outcome reported, were included.

Methods

Scopus, Cochrane, PubMed, EMBASE and, MEDLINE databases were electronically searched. Systematic review included 11 experimental studies, representing 515 participants with PCOS, out of which 2 randomized controlled trials (RCT’s) were included for meta-analysis. Random effects model was applied using Review Manager Software Version 5.4.1 and strength of evidence was assessed using GRADEpro Guideline Development Tool, 2020. This systematic review and meta-analysis was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42021229619.

Results

Meta-analysis showed that YT may significantly decrease menstrual irregularity (MD -0.41, 95% CI -0.74 to -0.08), clinical hyperandrogenism (MD -0.70, 95% CI -1.15 to -0.26), fasting blood glucose (FBG) (MD -0.22 mmol/L, 95% CI -0.44 to -0.01), fasting insulin (FI) (MD -28.21 pmol/L, 95% CI -43.79 to -12.63) and HOMA-IR value (MD -0.86, 95% CI -1.29 to -0.43). Strength of evidence was low.

Conclusions

YT may have beneficial effects on health outcomes in women suffering from PCOS. However, low strength of evidence suggests need of conducting well-designed RCT’s to assess the efficacy of YT for PCOS.

Key messages

This systematic review and meta-analysis adds to the knowledge about effects of YT on health outcomes of women with PCOS.
1304Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the EPIC study
Authors: Breeur Marie , Ferrari Pietro , Schmidt Julie , Travis Ruth , Key Tim , Johansson Mattias , Dossus Laure , Jenab Mazda , Rinaldi Sabina , Gunter Marc , Viallon Vivian
Published: September 2021

Background

Metabolomics studies in cancer epidemiology have mostly focused on single metabolite-cancer site associations. Pan-cancer analyses may have larger statistical power when identifying metabolites showing consistent associations across cancer sites, while allowing the identification of site-specific associations.

Methods

Data from seven cancer-specific case-control studies nested within the European Prospective Investigation into Cancer and Nutrition Cohort (EPIC) were pooled, resulting in a total sample of 7,957 case-control pairs from eight cancer types (breast, colorectal, endometrial, gallbladder, kidney, localized prostate and advanced prostate cancer, and hepatocellular carcinoma). A total of 117 pre-diagnostic blood metabolites were measured. After clustering the most highly correlated ones together, we studied the association between 50 features (metabolites or clusters of metabolites) and cancer risk in multivariate penalized conditional logistic regression models controlled for body mass index using the data shared lasso.

Results

We identified: (i) 8 features with consistent associations across cancer sites: e.g., glutamine and C4-acylcarnitine, one cluster of lysophosphatidylcholines and one of phosphatidylcholines were inversely associated with cancer, while C10-acylcarnitine, valine and proline showed positive associations; (ii) 11 features with heterogeneous associations across cancer sites: e.g., arginine was positively associated with colorectal cancer only, while one cluster of sphingomyelins was associated inversely with hepatocellular carcinoma and positively with endometrial cancer.

Conclusions

Our pan-cancer analysis notably identified metabolites showing consistent associations with cancer risk across different cancer-types.

Key messages

Our results could lead to the identification of common pathways shared across different cancer types.
20Forest loss shapes the landscape suitability of Kyasanur Forest disease in the Western Ghats, India
Authors: Walsh Michael , Mor Siobhan , Maity Hindol , Hossain Shah
Published: September 2021

Background

Anthropogenic pressure in biodiversity hotspots is increasingly recognised as a major driver of the spillover and expansion of zoonotic disease. In the Western Ghats region of India, a devastating tick-borne zoonosis, Kyasanur Forest disease (KFD), has been expanding rapidly beyond its endemic range in recent decades. While it has been suggested that anthropogenic pressure in the form of land use changes that lead to the loss of native forest may be directly contributing to the expanding range of KFD, clear evidence has not yet established the association between forest loss and KFD risk.

Methods

The current study sought to investigate the relationship between KFD landscape suitability and both forest loss and mammalian species richness to inform its epidemiology and infection ecology. Forty-seven outbreaks of KFD between 1 January, 2012 and 30 June, 2019 were modelled as an inhomogeneous Poisson process.

Results

Both forest loss (relative risk (RR) = 1.83; 95% C.I. 1.33 – 2.51) and mammalian species richness (RR = 1.29; 95% C.I. 1.16 – 1.42) were strongly associated with increased risk of KFD.

Conclusions

These results provide the first evidence of a clear association between increasing forest loss and risk for KFD. Moreover, the findings also highlight the importance of forest loss in areas of high biodiversity. This evidence supports integrative approaches to public health that incorporate conservation strategies simultaneously protective of humans, animals, and the environment.

Key messages

The association between deforestation and KFD risk suggest potential benefit in leveraging conservation efforts in the service of public health.
1402Thyroid stimulating hormone (TSH) is associated with general and abdominal obesity in girls during puberty
Authors: Wang Yingying
Published: September 2021

Background

Childhood is an important public health issue. Although both thyroid hormone and menarche are known to play a role in body metabolism and energy expenditure, no population-based study has been conducted to investigate the impact of TSH on adipogenesis among population-based girls around puberty.

Methods

A multi-stage cluster sampling method was used to select one junior middle school from each of 4 study areas: Minhang District in Shanghai, Haimen City in Jiangsu Province, Yuhuan City and Deqing County in Zhejiang Province. A total of 474 girls aged 11 to 14 years from 4 schools were enrolled. Information on demographic factors and puberty stage were collected, and anthropometric measurements and thyroid hormones were determined. Multivariate logistic regression models were used to assess the associations of Thyroid stimulating hormone (TSH) with the risk of obesity measured by body mess index (BMI) and waist circumference (WC).

Results

Of the 474 girls, the prevalences of BMI-based general obesity and WC-based abdominal obesity were 19.8% (94/474) and 21.7% (103/474), respectively. Compared with normal weight girls, the mean serum TSH concentration was significantly higher in BMI-based general overweight or obese girls (P = 0.037), but not in WC-based central overweight or obese girls (P = 0.173). In the multiple logistic regression models, for girls with highest tertile of serum TSH concentration relative to those in the lowest tertile, the odds ratios were 2.58 (95% CI 1.32 to 5.04) and 2.50 (95% CI 1.30 to 4.81) for overweight or obesity based on BMI and WC after adjustment for puberty stage and other covariates.

Conclusions

Serum TSH concentration was positively associated with both general and abdominal obesity in school-age girls and the association was independent of puberty.

Key messages

thyroid stimulating hormone; general obesity; central obesity; school-aged girls; puberty
1334Appetitive behaviors in school-age and their genetic and environmental predisposition
Authors: Warkentin Sarah , Severo Milton , Fildes Alison , Oliveira Andreia
Published: September 2021

Background

Given the great variability in adiposity and the exposure to obesogenic food environments, it has been suggested that individuals respond in divergent ways to the environment they live in. Our aim was to explore the genetic and environmental contribution of variations on appetitive behaviors in 10-year-old Portuguese children.

Methods

Participants were twins from the Generation XXI cohort (n = 86 pairs). Appetitive behaviors at 10 years was assessed through the Children Eating Behavior Questionnaire. Intra-class correlations for appetitive behaviors were calculated for monozygotic and dizygotic twins, and structural equation modelling was conducted to estimate genetic (A), shared (C) and non-shared (E) environmental variances.

Results

Twins were mainly dizygotic (65%), and a third was classified as having excess weight (30.2%). For all appetitive behaviors, with exception to Emotional Undereating, moderate to strong heritability were found and non-shared environmental effects contributed to appetite variability. For Emotional Undereating, environmental effects seem to be more important than genetic effects (C: 0.81; 95%CI 0.71;0.88 and E: 0.19; 95%CI 0.12;0.29).

Conclusions

There is a significant genetic contribution, followed by non-shared environmental effects, on appetitive behaviors in school-age years. Results indicate that Emotional Undereating was not heritable, being explained by shared and non-shared environmental factors.

Key messages

Appetitive behaviors among 10-year-olds seem to be genetically determined, with exception to Emotional Undereating, which showed to be explained by environmental factors. Understanding which genes are associated with child appetitive behaviors would give an insight in biological and behavioral influences on child eating and obesity risk.
1070An online searchable database of example causal diagrams to make them easier to construct
Authors: Watkins Tim
Published: September 2021

Focus of Presentation

Most researchers do not use causal diagrams, in this case meaning directed acyclic graphs (DAGs), despite being widely recommended in epidemiology. They can help to identify the biases that might lead to faulty conclusions or suggest variables for which data should be collected and included in a model. Seeking to understand this reluctance and develop alternative strategies that might increase the use of causal diagrams, we searched the cognitive science literature for potential reasons and suggestions.

Findings

Insights from cognitive psychology led to a better understanding of the barriers that might underlie the reluctance to use causal diagrams. This includes our built-in desire for cognitive ease and suggests that strategies which lower the effort required to create a diagram may help. We explain these findings using example projects from neuropsychiatry big data research and describe how an online resource we have created has helped.

Conclusions/Implications

A causal diagram website has been created that aims to lower the effort needed to create a diagram for a study. It contains tutorials and a terminology guide, as well as links to other tutorials; a guide to software and other resources that might be used; and a searchable database of example causal diagrams with links to published articles that include them.

Key messages

A website has been developed to help overcome barriers to the use of causal diagrams. With contributions welcome.
1478Extreme daily numbers of general practice encounters of asthma and allergic rhinitis in Australia
Authors: Waudby Charlotte , Osborne Nicholas , Muscatello David
Published: September 2021

Background

Asthma affects approximately 11% of Australia’s population and allergic rhinitis 19%. Grass pollen is associated with asthma and allergic rhinitis exacerbations. This study tested the hypothesis that days with extreme numbers of general practice (GP) encounters for asthma and allergic rhinitis aligned with grass pollen season.

Methods

The MedicineInsight GP database contains longitudinal data on persons attending a sample of Australian GPs. We created time series of daily counts of asthma and allergic rhinitis encounters by state and territory to identify extreme encounter days; days with counts above the 99th percentile.

Results

Of 3,036,678 attendances during the study period, 2.4% were for asthma. There were 83 extreme encounter days during April to December, across Australia. Victoria and South Australia had the highest increase in attendances on extreme days.

Allergic rhinitis encounters represented 0.9% of attendances. Of the 69 extreme allergic rhinitis encounter days across Australia, Victoria and Australian Capital Territory had the highest increase in attendances.

Allergic rhinitis extreme days were clustered between mid-October and early December (72%), compared to 22% of the asthma extreme days.

Conclusions

Extreme asthma GP encounters were not as strongly associated with grass pollen season compared to allergic rhinitis encounters. Victoria had a high number of encounters on asthma and allergic rhinitis extreme days, many associated with thunderstorm asthma.

Key messages

Extreme asthma encounter days can be associated with cooler months, grass pollen season and school holidays. Extremes allergic rhinitis presentation days were aligned with grass pollen season.
760Multi-stage models of cancer and disease
Authors: Webster Anthony
Published: September 2021

Background

Since Armitage and Doll's publication of “a multi-stage theory of carcinogenesis” in 1954, the multi-stage model has underpinned our conceptual understanding of cancer. In the last few years the model has been applied to other diseases, such as Amyotrophic Lateral Sclerosis (Motor Neurone Disease), providing new insight into how the disease can arise and progress.

Methods

The multi-stage model is simplified and generalised. The result is a simple mathematical toolkit to describe carcinogenesis or other multi-stage models of disease, with simple formulae corresponding to pictorial diagrams of the multi-stage process. Important practical issues are described regarding the fitting of data and the use of multi-stage models to interpret results.

Results

Relationships between established cancer models are clarified, and derivations are simplified. We provide examples and highlight pitfalls of fitting multistage models to data. It is explained how genetic markers and the multi-stage paradigm can provide new insights into mechanisms of disease. Limitations of the model are discussed in the context of recent cancer research.

Conclusions

A simple mathematical recipe can convert biologically-motivated models for each step in a disease’s progression, into a mathematical model. The framework provides a mathematical toolkit to study the failure of complex systems, biological or otherwise, simplifying the formulation and interpretation of multi-stage models.

Key messages

Multi-stage models are increasingly easy to use and understand. When combined with big data and genetic markers for stratification, they offer a new tool for epidemiological studies.
323Breast and cervical cancer screening and outcomes in NSW mental health service consumers
Authors: Wilson Elizabeth , Tervonen Hanna , Currow David , Sara Grant
Published: September 2021

Focus of Presentation

This presentation describes methods and findings from the NSW Mental Health Living Longer (MHLL) Program. MHLL involves population-wide data linkage that combines records from nine NSW data collections. Our collection includes over 120 million records for more than nine million people. This presentation focuses on the use of linked data to develop indicators to support reporting on premature cancer mortality for people living with mental illness. We will use these indicators to identify variation in care, assess areas for targeted intervention, and evaluate the effectiveness of research translation into safer and more effective care.

Findings

This work will be finalised by August 2020. We will use regression techniques to examine predictors of participation in breast and cervical cancer screening for women who use mental health services in NSW. These results will be used to assess geographical variation in risk-adjusted screening participation rates. We will also present methods and results for measuring incidence and stage at presentation, as well as 12 month and 5 year survival for women who use mental health services compared to other women in NSW.

Conclusions/Implications

If cancer survival is a key measure of the effectiveness of healthcare systems, then reduced survival in people with mental health problems reflects less effective health care. Improving screening and treatment services is likely to be the most important strategy for reducing the cancer mortality gap for people with mental illness.

Key messages

Health systems must move from recognition to action if we are to reduce premature cancer mortality in people living with mental illness.
381In-hospital mortality for infants with HIE who received therapeutic hypothermia: a propensity score-matched cohort study
Authors: Wollny Krista , Mohammad Khorshid , Wood Stephen , Hicks Matthew , Skiffington Janice , Cherak Stephana J. , Metcalfe Amy
Published: September 2021

Background

In 2016, the Academic Medical Center Neonatal Encephalopathy Task Force recommended therapeutic hypothermia (TH) as the standard-of-care for hypoxic ischemic encephalopathy (HIE). However, not all infants who meet the criteria for TH receive this treatment. The purpose of this study was to compare the risk of mortality for infants with HIE who did and did not receive TH, after accounting for confounders associated with receipt of TH.

Methods

A retrospective cohort study was conducted using the 2016 National Inpatient Sample (NIS), which contains 20% of all hospital discharges in the United States. Infants were included if they were diagnosed with HIE and were eligible for TH. Nearest-neighbor propensity score-matching (1:1) without replacement was performed prior to logistic regression analysis. The average treatment effect of TH was calculated to estimate the odds of mortality.

Results

There were 211 infants with HIE who received TH, which is an estimated proportion of 24.8% (95% CI: 20.9-29.1%). Infants who received TH were more likely to have a seizure (p < 0.05), be transferred from another hospital (p < 0.001), and have the highest Risk of Mortality scores (p < 0.05). The odds of mortality were 0.91 (95% CI: 0.85-0.97) for infants that received TH, compared to those who did not.

Conclusions

Receipt of TH varied across patient groups and was associated with clinical risk factors. The odds of in-hospital mortality were lower in infants who received TH.

Key messages

Infants who received TH had a decreased risk of in-hospital mortality compared to infants who did not receive TH.
485Prospective associations between sex hormone-binding globulin and risk of type 2 diabetes
Authors: Woo Hye Won , Shin Min-Ho , Choi Bo Youl , Kim Mi Kyung
Published: September 2021

Background

Circulating sex hormone–binding globulin levels are inversely associated with insulin resistance. However, epidemiologic evidence on the association of sex hormone-binding globulin (SHBG) and the risk of developing diabetes is limited. This study aimed to evaluate the prospective associations between serum SHBG level and risk of type 2 diabetes (T2D) among adults ≥ 40 years old in the Yangpyeong and Namwon cohort.

Methods

A total of 4,383 (1,651 men and 2,732 women) participants who did not have T2D were enrolled. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (27,146 person-years), 284 T2D cases were newly diagnosed.

Results

Significant dose-response inverse associations were observed between serum SHBG (tertiles) and T2D in women, even after controlling for baseline fasting glucose (incidence rate ratio, IRR=0.42, 95% CI = 0.26–0.68, P for trend = <.001 in the highest tertile). Similar significant linear trends were found among menopausal women, and the inverse associations persisted across participant subgroups with diabetes risk profiles. However, there were no significant associations with serum SHBG in men. When we examined the association, except for men with higher levels of hs-CRP (≥ 3 mg/L) and HOMA-IR (≥ 2.5) at baseline, the non-significant associations did not change (IRR=1.45, 95% CI = 0.78–2.70, P for trend=0.167 in the highest tertile). The sex-specific differences in associations between serum SHBG and T2D risk were statistically significant (P for interaction=0.005).

Conclusions

Serum SHBG may be inversely associated with T2D in women, but not in men.

Key messages

Circulating SHBG may play different roles in the development of T2D in men and women.
165Ethnic differences in type 2 diabetes mortality and hospitalisation rates in a New Zealand population1994-2018
Authors: Yu Dahai , Osuagwu Levi , Pickering Karen , Baker John , Cutfield Richard , Orr-Walke Brandon , CaI Yamei , Zhao Zhanzheng , Simmons David
Published: September 2021

Background

Type 2 Diabetes (T2DM) affects different populations disproportionately including in New Zealand (NZ), where long-term temporal trends in cause-specific clinical outcomes between Māori, European and Pacific people remain unclear.

Methods

Data from patients with T2DM, aged 35-84 years enrolled 1994-2018 in a NZ primary care audit programme (the Diabetes Care Support Service) were linked with national death registration, hospitalisation, pharmaceutical claims and primary care databases. Cause-specific death and hospitalisation rates were adjusted for gender, age, smoking, obesity, social-economic status and time periods by age-period-cohort models.

Results

Overall, 79,912 (50.6% female, mean-age 56±15 years, median follow-up 9.7 years) patients with T2DM were enrolled. For Europeans vs Māori, adjusted incidence rates ratio (IRR) and absolute risk difference /1000 person-years were 1.96 (95% CI: 1.80- 2.14) and 22.85 (19.93-25.77) for all-cause mortality, 1.93 (1.63-2.29) and 6.97 (5.14-8.80) for cardiovascular (CVD) mortality, 1.64 (1.40-1.93) and 3.08 (2.25-3.92) for cancer mortality, 1.26 (1.25-1.28) and 42.70 (41.32-44.08) for CVD hospitalisation, 1.31 (1.28-1.34) and 44.76 (42.37-47.15) for cancer hospitalisation, 2.05 (1.96-2.14) and 31.44 (29.67-33.21) for end-stage renal disease (ESRD) hospitalisation. Pacific rates were significantly less than Māori, but higher than Europeans for ESRD (IRR:1.59 (1.52-1.67)) and CVD (1.09 (1.07-1.10)) hospitalisation.

Conclusions

Poorer health outcomes have persisted among Māori and Pacific people with T2DM for >20 years. New policies supporting more intensive management of T2DM are urgently needed. Differences in outcomes between Māori and Pacific people warrant further research.

Key messages

Outcome disparities have persisted among Māori and Pacific people with T2DM for >20 years.