300 results on '"Mark McEvoy"'
Search Results
2. Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
- Author
-
Nathan Gaddis, Ravi Mathur, Jesse Marks, Linran Zhou, Bryan Quach, Alex Waldrop, Orna Levran, Arpana Agrawal, Matthew Randesi, Miriam Adelson, Paul W. Jeffries, Nicholas G. Martin, Louisa Degenhardt, Grant W. Montgomery, Leah Wetherill, Dongbing Lai, Kathleen Bucholz, Tatiana Foroud, Bernice Porjesz, Valgerdur Runarsdottir, Thorarinn Tyrfingsson, Gudmundur Einarsson, Daniel F. Gudbjartsson, Bradley Todd Webb, Richard C. Crist, Henry R. Kranzler, Richard Sherva, Hang Zhou, Gary Hulse, Dieter Wildenauer, Erin Kelty, John Attia, Elizabeth G. Holliday, Mark McEvoy, Rodney J. Scott, Sibylle G. Schwab, Brion S. Maher, Richard Gruza, Mary Jeanne Kreek, Elliot C. Nelson, Thorgeir Thorgeirsson, Kari Stefansson, Wade H. Berrettini, Joel Gelernter, Howard J. Edenberg, Laura Bierut, Dana B. Hancock, and Eric Otto Johnson
- Subjects
Medicine ,Science - Abstract
Abstract Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
- Published
- 2022
- Full Text
- View/download PDF
3. Association of serum ergothioneine with alcohol consumption and serum asymmetric dimethyl-l-arginine among middle-aged and older adults in the Hunter Community Study
- Author
-
Salvatore Sotgia, Arduino A. Mangoni, Stephen Hancock, Angelo Zinellu, Ciriaco Carru, and Mark McEvoy
- Subjects
Cardiometabolic diseases ,Health-conscious food pattern ,Alcohol intake ,Ergothioneine ,Antioxidants ,Asymmetric dimethyl-L-arginine ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Among plasma metabolites linked with a health-conscious food pattern (HCFP) identified in the Malmö Diet and Cancer epidemiological study, circulating ergothioneine (ERT) concentrations exhibited the strongest independent association with reduced risk of cardiometabolic disease and all-cause mortality and were also related to alcohol consumption. Thus, we first assessed whether alcohol intake and ERT were similarly associated in participants of the Hunter Community Study (HCS) that did not follow an HCFP-based diet. Then, we sought to identify the presence of associations with some biomarkers associated with cardiovascular disease. In a multivariable adjusted, robust regression analysis, compared to non-drinkers, safe drinkers had, on average, a serum ERT concentration 0.112 (95% CI: 0.0–0.225; P = 0.051) units higher and moderate-hazardous drinkers had a serum ERT concentration 0.240 (95% CI: 0.093–0.387; P = 0.001) units higher. Moreover, stepwise multiple linear regression shows that age (P = 0.025), and asymmetric dimethyl-l-arginine (ADMA) (P = 0.001) were independently associated with serum ERT concentrations, independently of age, sex, education, household income, marital status, and health status of participants, or possible alcohol-induced organ damage. The relationship between ERT and ADMA offers a potential explanation for the interplay between ERT, and decreased risk of cardiometabolic disease and all-cause mortality. Also, it provides new mechanistic insights into the association between alcohol consumption and cardiovascular diseases, possibly mediated by ADMA metabolic pathways.
- Published
- 2023
- Full Text
- View/download PDF
4. Using the AUSDRISK score to screen for pre‐diabetes and diabetes in GP practices: a case‐finding approach
- Author
-
Kerry Fleming, Natasha Weaver, Roseanne Peel, Alexis Hure, Mark McEvoy, Elizabeth Holliday, Martha Parsons, Shamasunder Acharya, Judy Luu, John Wiggers, Chris Rissel, Priyanga Ranasinghe, Ranil Jayawardena, Samir Samman, and John Attia
- Subjects
diabetes ,pre‐diabetes ,prevention ,primary care ,AUSDRISK ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Objective: To identify the optimal AUSDRISK threshold score to screen for pre‐diabetes and diabetes. Methods: A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre‐diabetes (5.7–6.4% or 39–47 mmol/mol), or normal (
- Published
- 2022
- Full Text
- View/download PDF
5. Causal association pathways between fetuin-A and kidney function: a mediation analysis
- Author
-
Philip Etabee Bassey, Pawin Numthavaj, Sasivimol Rattanasiri, Piyamitr Sritara, Mark McEvoy, Boonsong Ongphiphadhanakul, and Ammarin Thakkinstian
- Subjects
Medicine (General) ,R5-920 - Abstract
Objective Body mass index (BMI), uric acid, diabetes mellitus, and hypertension are risk factors for reduced kidney function and are associated with fetuin-A levels, but their causal pathways remain unclear. The objective of this study was to investigate this knowledge gap. Methods A repeated cross-sectional design was used to assess causal pathway effects of fetuin-A on the estimated glomerular filtration rate (eGFR), which is mediated through BMI, uric acid, diabetes mellitus, and hypertension. Results Among 2305 participants, the mean eGFR at baseline decreased from 98.7 ± 23.6 mL/minute/1.73 m 2 in 2009 to 92.4 ± 22.9 mL/minute/1.73 m 2 in 2014. Fetuin-A was significantly associated with eGFR , suggesting that increasing fetuin-A levels predict a decrease in eGFR. Additionally, the indirect effect of fetuin-A on eGFR, as assessed through BMI, was also significant. The effects of fetuin-A on eGFR through other mediation pathways showed variable results. Conclusions Our study revealed a possible role of fetuin-A in the etiology of declining renal function through mediating body mass index, uric acid, diabetes mellitus, and hypertension via complex causal pathways. Further studies to clarify these mediated effects are recommended.
- Published
- 2022
- Full Text
- View/download PDF
6. Factors to consider during the implementation of nutrition and physical activity trials for people with psychotic illness into an Australian community setting
- Author
-
Doreen Mucheru, Samantha Ashby, Mary-Claire Hanlon, Mark McEvoy, and Lesley MacDonald-Wicks
- Subjects
Lifestyle interventions ,Psychotic illness ,Mental health ,Knowledge translation ,Community managed organisations ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Research in lifestyle interventions focusing on nutrition and physical activity in people living with psychotic illness, highlights anthropometric and metabolic benefits of these interventions. However, little is known about potential factors to consider during implementation into real-world contexts. Community-managed organisations (CMOs) that provide services for people with mental illness, offer an ideal implementation context for lifestyle interventions. Successful translation of lifestyle interventions into CMOs may be achieved though considering the factors associated with program access and delivery in these settings. This study primarily aimed to identify the factors that affect program access in a local CMO from the perspective of consumers and staff. The secondary aim was to describe the elements that impact on program delivery from the perspective of staff. Methods Thirteen semi-structured interviews were conducted with 6 consumers and 7 staff in a CMO in regional Australia. Topics explored in interviews were based on implementation concepts identified in the “Integrated Promoting Action on Research Implementation in Health Systems” (i-PARIHS) knowledge translation framework. Thematic data analysis was conducted using Nvivo software. Results Emergent themes on issues that influenced program access were (1) consumer financial status, domestic responsibilities, and health; (2) the design and delivery of programs; (3) structure and practices of the organisation; (4) attitude, skills and effort of staff involved in program delivery; and (5) social connections and stigma experienced by consumers during program access. Moreover, staff perceptions on elements that impacted program delivery highlighted themes on consumer attendance and interest in prospective programs, availability and restrictions to the use of funding, as well as the organisational structure and practices. Conclusions The factors affecting program access and delivery can generally be managed or planned for during the design of lifestyle interventions and subsequent translation into the CMO context. However, resolution of issues related to consumer financial status and health requires the collaboration of various government sectors for system-wide solutions.
- Published
- 2020
- Full Text
- View/download PDF
7. Change in exhaled nitric oxide during peanut challenge is related to severity of reaction
- Author
-
Elizabeth Percival, Rani Bhatia, Kahn Preece, Mark McEvoy, Adam Collison, and Joerg Mattes
- Subjects
Peanut ,Allergy ,Anaphylaxis ,FeNO ,Fraction exhaled nitric oxide ,Skin prick test ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Peanut allergy affects 3% of Australian children and has a higher risk of anaphylaxis than most food allergies. Predicting who is likely to develop anaphylaxis is still an inexact science. The fraction of exhaled nitric oxide (FeNO) shows promise as a biomarker involved in peanut allergy, as nitric oxide plays a role in inhibiting mast cell degranulation which is relevant in anaphylaxis, where mast cell degranulation plays a mediator role. The aim of this study was to assess the change in FeNO in children during peanut challenge. Methods Thirty-six children aged from 5 to 17 years were recruited for open-labelled peanut challenge. Participants had skin prick test to peanut performed, and serum collected for Ara h2 specific IgE and peanut specific IgE. FeNO was measured by portable device (NIOX VERO) prior to and throughout the peanut challenge. Results When grouped according to reaction type at peanut challenge (anaphylaxis, clinical allergy not anaphylaxis and tolerant), there were significant differences in the mean change in FeNO measurement between the anaphylaxis group and the clinical allergy, not anaphylaxis group (p = 0.005), and between the anaphylaxis group and tolerant group (p
- Published
- 2020
- Full Text
- View/download PDF
8. Loddon Mallee healthcare worker COVID-19 study—protocol for a prospective cohort study examining the health and well-being of rural Australian healthcare workers during the COVID-19 pandemic
- Author
-
Stephen Begg, Mark McEvoy, Carol Parker, Angela Crombie, Peter Faulkner, Anne McEvoy, Laura Bamforth, and Gabriel Caccaviello
- Subjects
Medicine - Abstract
Introduction The COVID-19 pandemic is creating immense psychosocial disturbance. While global, broad-based research is being conducted, little is known about the effects of the COVID-19 pandemic on health and well-being or how protective and resilience factors influence the human response in Australian rural and regional communities. Rural and regional communities often have less resources to deal with such public health emergencies and face additional environmental adversity. Healthcare workers, including those in rural and regional areas, have felt the immediate impacts of COVID-19 in a multitude of ways and these impacts will continue for years to come. Therefore, this study aims to describe and understand the impacts of the COVID-19 pandemic on the rural and regional healthcare workforce within the Loddon Mallee region, Victoria, Australia.Methods and analysis This prospective cohort of rural and regional healthcare workers will be recruited and followed over 3 years to examine the effects of the COVID-19 pandemic on their health and well-being. Self-administered online questionnaires will be administered every 6 months for a 36-month period. Multiple outcomes will be assessed; however, the primary outcomes are emotional health and well-being and psychological resilience. Emotional health and well-being will be measured using validated instruments that will assess multiple domains of the emotional health and well-being continuum.Linear and logistic regression and latent growth curve modelling will be used to examine the association between baseline and follow-up participant emotional health, well-being and resilience while adjusting for potentially time-varying confounding variables. Participant characteristics measured at baseline will also be tested for association with incident health, morbidity, mortality and health service utilisation outcomes at follow-up.Ethics and dissemination Ethical approval has been obtained through the Bendigo Health Human Research Ethics Committee. The study findings will be disseminated through international conferences, international peer-reviewed journals and social media.Trial registration number ACTRN12620001269921.
- Published
- 2021
- Full Text
- View/download PDF
9. Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD Study) – study protocol for a randomised placebo-controlled trial in Australia
- Author
-
Roseanne Peel, Alexis Hure, John Wiggers, Mark McEvoy, Elizabeth Holliday, Andrew Searles, Penny Reeves, Priyanga Ranasinghe, Ranil Jayawardena, Samir Samman, Shamasunder Acharya, Judy Luu, Chris Rissel, and John Attia
- Subjects
Zinc supplementation ,Healthy lifestyle ,Pre-diabetes ,Australia ,Adults ,Medicine (General) ,R5-920 - Abstract
Abstract Background Diabetes is increasing in incidence, morbidity and treatment costs globally, hence prevention strategies need to be explored. Animal studies and some human data have shown that zinc can improve glycaemic control, but the impact of this effect in a pre-diabetic population remains uncertain. This study is designed to investigate whether zinc gluconate and lifestyle coaching can improve glucose handling and ultimately reduce diabetes incidence in an at-risk pre-diabetic population in Australia. Methods/design The study will be a randomised, placebo-controlled, double-blind clinical trial. The study will be conducted at the Hunter New England Local Health District New South Wales (NSW), Australia. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7–6.4) male and female participants (n = 410) aged 40–70 years will be recruited through the Diabetes Alliance Network, a collaboration of diabetes specialists and general practitioner practices. All participants will be given routine care to encourage healthy lifestyle changes using a telephone coaching service (Get Healthy Information and Coaching Service, NSW Health) and then randomised to receive a supplement, either zinc gluconate (equivalent to 30 mg of elemental zinc) or placebo of identical appearance for 12 months. The identity of the supplements will be blinded to both research personnel and the participants. Participants will be asked to complete medical, lifestyle and dietary surveys and will have baseline and final visits at their general practitioner practice. Primary outcomes will be HbA1c and insulin sensitivity collected at baseline and at 1, 6 and 12 months; secondary outcomes will include fasting blood glucose, fasting cholesterol, blood pressure and body mass index. The primary efficacy endpoint will be judged at 6 months. Discussion This study will generate new evidence about the potential for health coaching, with or without zinc supplementation, to improve glucose handling and ultimately to reduce progression from pre-diabetes to diabetes. Trial registration Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.
- Published
- 2019
- Full Text
- View/download PDF
10. Discovery Genome-Wide Association Study of Body Composition in 4,386 Adults From the UK Biobank’s Pilot Imaging Enhancement Study
- Author
-
Katherine M. Livingstone, Mun Hua Tan, Gavin Abbott, Rachel L. Duckham, Larry Croft, Joey Ward, Mark McEvoy, Michelle A. Keske, Christopher Austin, and Steven J. Bowe
- Subjects
dual energy X-ray absorptiometry ,genome-wide association study ,loci ,bone mass ,fat mass ,lean mass ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Body composition (fat, skeletal muscle and bone mass) is an important determinant of overall health and risk of endocrine disorders such as type 2 diabetes and osteoporosis. Although diet and physical activity are strongly implicated, body composition is also heritable. We conducted a discovery genome-wide association study on 31 phenotypes from the three-compartment body composition model (fat, lean and bone mass) in a set of 4 386 individuals (n = 2 109 males, n = 2 294 females) from the UK Biobank pilot imaging enhancement program that underwent a dual energy X-ray absorptiometry (DXA) scan for assessment of body composition and genetic screening. From 6 137 607 imputed single nucleotide polymorphisms (SNPs) we identified 17 body composition loci (P
- Published
- 2021
- Full Text
- View/download PDF
11. Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies
- Author
-
Bhavani Shankara Bagepally, Usa Chaikledkaew, Yogesh Krishnarao Gurav, Sitaporn Youngkong, and Mark McEvoy
- Subjects
Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objectives To conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure.Research design and methods The study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I2 statistic.Results A total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I2=0%), US$3857.34 (95% CI US$−7293.93 to US$15 008.61, I2=45.9%), US$37 577.74 (95% CI US$−649.02 to US$75 804.50, I2=92.4%) and US$14 062.42 (95% CI US$8168.69 to US$19 956.15, I2=86.4%), respectively. GLP1s were statistically significantly cost-effective compared with insulins, but not compared with DPP4i, sulfonylureas, and TZDs. Among GLP1s, liraglutide was more cost-effective compared with lixisenatide, but not compared with exenatide, with corresponding pooled INBs of US$4555.09 (95% CI US$3992.60 to US$5117.59, I2=0) and US$728.46 (95% CI US$−1436.14 to US$2893.07, I2=0), respectively.Conclusion GLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs.PROSPERO registration number CRD42018105193.
- Published
- 2020
- Full Text
- View/download PDF
12. Identification of nine new susceptibility loci for endometrial cancer
- Author
-
Tracy A. O’Mara, Dylan M. Glubb, Frederic Amant, Daniela Annibali, Katie Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, Maxine M. Chen, Timothy H. T. Cheng, Christine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous-Bous, Kamila Czene, Felix Day, Joe Dennis, Jeroen Depreeuw, Jennifer Anne Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny Fung, Montserrat García-Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Hoivik, Elizabeth G. Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R. B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A. W. Rogers, Matthias Rübner, Ingo Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick Schumacher, Rodney J. Scott, V. Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao-Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M. J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong-Bing Xiang, Hannah P. Yang, Herbert Yu, Wei Zheng, Paul D. P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle, and Deborah J. Thompson
- Subjects
Science - Abstract
Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.
- Published
- 2018
- Full Text
- View/download PDF
13. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
- Author
-
Annah B. Wyss, Tamar Sofer, Mi Kyeong Lee, Natalie Terzikhan, Jennifer N. Nguyen, Lies Lahousse, Jeanne C. Latourelle, Albert Vernon Smith, Traci M. Bartz, Mary F. Feitosa, Wei Gao, Tarunveer S. Ahluwalia, Wenbo Tang, Christopher Oldmeadow, Qing Duan, Kim de Jong, Mary K. Wojczynski, Xin-Qun Wang, Raymond Noordam, Fernando Pires Hartwig, Victoria E. Jackson, Tianyuan Wang, Ma’en Obeidat, Brian D. Hobbs, Tianxiao Huan, Hongsheng Gui, Margaret M. Parker, Donglei Hu, Lauren S. Mogil, Gleb Kichaev, Jianping Jin, Mariaelisa Graff, Tamara B. Harris, Ravi Kalhan, Susan R. Heckbert, Lavinia Paternoster, Kristin M. Burkart, Yongmei Liu, Elizabeth G. Holliday, James G. Wilson, Judith M. Vonk, Jason L. Sanders, R. Graham Barr, Renée de Mutsert, Ana Maria Baptista Menezes, Hieab H. H. Adams, Maarten van den Berge, Roby Joehanes, Albert M. Levin, Jennifer Liberto, Lenore J. Launer, Alanna C. Morrison, Colleen M. Sitlani, Juan C. Celedón, Stephen B. Kritchevsky, Rodney J. Scott, Kaare Christensen, Jerome I. Rotter, Tobias N. Bonten, Fernando César Wehrmeister, Yohan Bossé, Shujie Xiao, Sam Oh, Nora Franceschini, Jennifer A. Brody, Robert C. Kaplan, Kurt Lohman, Mark McEvoy, Michael A. Province, Frits R. Rosendaal, Kent D. Taylor, David C. Nickle, L. Keoki Williams, Esteban G. Burchard, Heather E. Wheeler, Don D. Sin, Vilmundur Gudnason, Kari E. North, Myriam Fornage, Bruce M. Psaty, Richard H. Myers, George O’Connor, Torben Hansen, Cathy C. Laurie, Patricia A. Cassano, Joohon Sung, Woo Jin Kim, John R. Attia, Leslie Lange, H. Marike Boezen, Bharat Thyagarajan, Stephen S. Rich, Dennis O. Mook-Kanamori, Bernardo Lessa Horta, André G. Uitterlinden, Hae Kyung Im, Michael H. Cho, Guy G. Brusselle, Sina A. Gharib, Josée Dupuis, Ani Manichaikul, and Stephanie J. London
- Subjects
Science - Abstract
Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.
- Published
- 2018
- Full Text
- View/download PDF
14. Cardiovascular disease lifestyle risk factors in people with psychosis: a cross-sectional study
- Author
-
Doreen Mucheru, Mary-Claire Hanlon, Linda E. Campbell, Mark McEvoy, and Lesley MacDonald-Wicks
- Subjects
Psychosis ,Nutrition ,Physical activity ,Smoking ,Lifestyle risk factors ,Cardiovascular disease ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background People with psychosis die on average 25 years earlier than those in the general population, with cardiovascular disease (CVD) contributing to much of the excess mortality. This cross-sectional study aimed to identify the relationship between lifestyle risk factors for CVD – poor nutrition, smoking and low physical activity levels – and dyslipidaemia, hypertension and hyperglycaemia while controlling for potential confounders in 1825 people from the Survey of High Impact Psychosis (SHIP) in Australia. We also aimed to identify clustering patterns of lifestyle risk factors and associated demographic variables. Methods Three logistic regressions were used to predict the effect of nutrition, smoking and physical activity on dyslipidaemia, hypertension and hyperglycaemia while controlling for clozapine use, sex and age. Clustering patterns of nutrition, smoking and physical activity were examined using the two-step cluster method which is based on hierarchical cluster analysis. Demographic variables associated with different clusters were identified using measures of association. Results Smoking status had a positive association with dyslipidaemia (adjusted odds ratio = 0.50; 95% confidence interval = 0.32–0.78; p = 0.002). Other cardiovascular disease lifestyle risk factors did not have a significant relationship with dyslipidaemia, hypertension and hyperglycaemia. Clustering patterns of lifestyle risk factors showed that younger men, with low education levels, and relying on a government pension, were most likely to display the poorest lifestyle risk behaviours. The largest cluster (42%) of participants was characterised by a mixed demographic profile and were most likely to display poor nutrition and low physical activity levels but less likely to smoke. Conclusions Only smoking status had a significant positive association with dyslipidaemia which could indicate that there are additional factors affecting the relationship between other cardiovascular lifestyle risk factors and dyslipidaemia, hypertension and hyperglycaemia in people with psychosis. Unknown confounders and traditional lifestyle risk factors may explain the high rates of CVD in this group. Clustering of lifestyle risk factors and their demographic profiles could help the design of intervention programs in people with psychosis.
- Published
- 2018
- Full Text
- View/download PDF
15. Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses
- Author
-
Jodie N. Painter, Tracy A. O'Mara, Andrew P. Morris, Timothy H. T. Cheng, Maggie Gorman, Lynn Martin, Shirley Hodson, Angela Jones, Nicholas G. Martin, Scott Gordon, Anjali K. Henders, John Attia, Mark McEvoy, Elizabeth G. Holliday, Rodney J. Scott, Penelope M. Webb, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Matthias Rübner, Per Hall, Kamila Czene, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo Runnebaum, Diether Lambrechts, Frederic Amant, Daniela Annibali, Jeroen Depreeuw, Adriaan Vanderstichele, Ellen L. Goode, Julie M. Cunningham, Sean C. Dowdy, Stacey J. Winham, Jone Trovik, Erling Hoivik, Henrica M. J. Werner, Camilla Krakstad, Katie Ashton, Geoffrey Otton, Tony Proietto, Emma Tham, Miriam Mints, Shahana Ahmed, Catherine S. Healey, Mitul Shah, Paul D. P. Pharoah, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Kyriaki Michailidou, Qin Wang, Jonathan P. Tyrer, John L. Hopper, Julian Peto, Anthony J. Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Jenny Chang‐Claude, Fergus J. Couch, Graham G. Giles, Vessela N. Kristensen, Angela Cox, Krina T. Zondervan, Dale R. Nyholt, Stuart MacGregor, Grant W. Montgomery, Ian Tomlinson, Douglas F. Easton, Deborah J. Thompson, and Amanda B. Spurdle
- Subjects
Cross‐disease analysis ,endometrial cancer ,endometriosis ,genome‐wide association study ,genetic correlation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
- Published
- 2018
- Full Text
- View/download PDF
16. Is osteoporosis an autoimmune mediated disorder?
- Author
-
Rosebella A. Iseme, Mark Mcevoy, Brian Kelly, Linda Agnew, Frederick R. Walker, and John Attia
- Subjects
Osteoporosis ,Autoantibodies ,Bone remodelling ,Bone mineral density ,Fractures ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
The last two decades have marked a growing understanding of the interaction occurring between bone and immune cells. The chronic inflammation and immune system dysfunction commonly observed to occur during the ageing process and as part of a range of other pathological conditions, commonly associated with osteoporosis has led to the recognition of these processes as important determinants of bone disease. This is further supported by the recognition that the immune and bone systems in fact share regulatory mechanisms and progenitor molecules. Research into this complex synergy has provided a better understanding of the immunopathogenesis underlying bone diseases such as osteoporosis. However, existing research has largely focussed on delineating the role played by inflammation in pathogenic bone destruction, despite increasing evidence implicating autoantibodies as important drivers of osteoporosis. This review shall attempt to provide a comprehensive overview of existing research examining the role played by autoantibodies in osteoporosis in order to determine the potential for further research in this area. Autoantibodies represent promising targets for the improved treatment and diagnosis of inflammatory bone loss.
- Published
- 2017
- Full Text
- View/download PDF
17. Treatment effects of renin-angiotensin aldosterone system blockade on kidney failure and mortality in chronic kidney disease patients
- Author
-
Phisitt Vejakama, Atiporn Ingsathit, Gareth J. McKay, Alexander P. Maxwell, Mark McEvoy, John Attia, and Ammarin Thakkinstian
- Subjects
Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Chronic kidney disease (CKD) is a leading cause of death before and after onset of end-stage renal disease (ESRD). Knowing treatments that can delay disease progression will lead to reduced mortality. We therefore aimed to estimate the effectiveness of renin angiotensin aldosterone system (RAAS) blockade on CKD progression. Methods We conducted a retrospective CKD cohort at Ubon Ratchathani province, Thailand from 1997 to 2011. ESRD was defined as estimated glomerular filtration rate (eGFR) 1 year (RAAS2). An augmented inverse-probability weighting (AIPW) method was used to estimate potential-outcome mean (POM) and average treatment-effect (ATE). Multi-logit and Poisson regressions were used for treatment and outcome models, respectively. Analyses were stratified by ESRD, death before/after ESRD for diabetic and non-diabetic groups. STATA 14.0 was used for statistical analyses. Results Among 15,032 diabetic patients, 2346 (15.6%), 2351 (18.5%), and 1607 (68.5%) developed ESRD, died before ESRD, and died after ESRD, respectively. Only RAAS2 effect was significant on ESRD, death before and after ESRD. The ESRD rates were 12.9%, versus 20.0% for RAAS2 and non-RAAS, respectively, resulted in significant risk differences (RD) of −7.2% (95% CI: -8.8%, −5.5%), and a numbers needed-to-treat (NNT) of 14. Death rates before ESRD for these corresponding groups were 14.4% (12.9%, 15.9%) and 19.6% (18.7%, 20.4%) with a NNT of 19. Death rates after ESRD in RAAS2 was lower than non-RASS group (i.e., 62.8% (55.5%, 68.9%) versus 68.1% (65.9%, 70.4%)) but this was not significant. RAAS2 effects on ESRD and death before ESRD were persistently significant in non-diabetic patients (n = 17,074) but not for death after ESRD with the NNT of about 15 and 16 respectively. Conclusions Receiving RAAS blockade for 1 year or longer could prevent both CKD progression to ESRD and premature mortality.
- Published
- 2017
- Full Text
- View/download PDF
18. Evaluation of rational nonsteroidal anti-inflammatory drugs and gastro-protective agents use; association rule data mining using outpatient prescription patterns
- Author
-
Oraluck Pattanaprateep, Mark McEvoy, John Attia, and Ammarin Thakkinstian
- Subjects
Data mining ,Association rule ,Apriori algorithm ,Prescription patterns ,Rational drug use ,Hospital ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Nonsteroidal anti-inflammatory drugs (NSAIDs) and gastro-protective agents should be co-prescribed following a standard clinical practice guideline; however, adherence to this guideline in routine practice is unknown. This study applied an association rule model (ARM) to estimate rational NSAIDs and gastro-protective agents use in an outpatient prescriptions dataset. Methods A database of hospital outpatients from October 1st, 2013 to September 30th, 2015 was searched for any of following drugs: oral antacids (A02A), peptic ulcer and gastro-oesophageal reflux disease drugs (GORD, A02B), and anti-inflammatory and anti-rheumatic products, non-steroids or NSAIDs (M01A). Data including patient demographics, diagnoses, and drug utilization were also retrieved. An association rule model was used to analyze co-prescription of the same drug class (i.e., prescriptions within A02A-A02B, M01A) and between drug classes (A02A-A02B & M01A) using the Apriori algorithm in R. The lift value, was calculated by a ratio of confidence to expected confidence, which gave information about the association between drugs in the prescription. Results We identified a total of 404,273 patients with 2,575,331 outpatient visits in 2 fiscal years. Mean age was 48 years and 34% were male. Among A02A, A02B and M01A drug classes, 12 rules of associations were discovered with support and confidence thresholds of 1% and 50%. The highest lift was between Omeprazole and Ranitidine (340 visits); about one-third of these visits (118) were prescriptions to non-GORD patients, contrary to guidelines. Another finding was the concomitant use of COX-2 inhibitors (Etoricoxib or Celecoxib) and PPIs. 35.6% of these were for patients aged less than 60 years with no GI complication and no Aspirin, inconsistent with guidelines. Conclusions Around one-third of occasions where these medications were co-prescribed were inconsistent with guidelines. With the rapid growth of health datasets, data mining methods may help assess quality of care and concordance with guidelines and best evidence.
- Published
- 2017
- Full Text
- View/download PDF
19. Progression of chronic kidney disease: an illness-death model approach
- Author
-
Phisitt Vejakama, Atiporn Ingsathit, Mark McEvoy, John Attia, and Ammarin Thakkinstian
- Subjects
Chronic kidney disease progression ,CKD progression ,Illness death model ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Chronic kidney disease (CKD) is a major contributor to mortality in the general population. Understanding the factors that drive this process will help delay progression of CKD. The study aimed to estimate the risks of kidney failure and death prior to and after the development of kidney failure among patients with pre-existing CKD, and to identify potential prognostic factors. Method Data were obtained from patients with CKD from Ubon Ratchathani province, Thailand from 1997 to 2011. The probability of each transition (i.e., CKD➔death (T1), CKD➔kidney failure (T2), and kidney failure➔death (T3)) was estimated using a competing risk model. A parametric survival model with restricted cubic spline function was applied to assess prognostic factors. Illness-death models were constructed for the 3 transitions. Among 32,106 patients with CKD, 5576 (17.4%), 4768 (14.9%), and 3056 (9.5%) respectively moved through T1, T2, and T3. Results Diabetics had 22.6%, 13.5%, and 60.7% higher risks of T1, T2, and T3 than non-diabetics respectively (p
- Published
- 2017
- Full Text
- View/download PDF
20. A Cross-Sectional Study of the Association between Autoantibodies and Qualitative Ultrasound Index of Bone in an Elderly Sample without Clinical Autoimmune Disease
- Author
-
Rosebella A. Iseme, Mark McEvoy, Brian Kelly, Linda Agnew, Frederick R. Walker, Michael Boyle, and John Attia
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Bone loss is characteristic of the ageing process and a common complication of many autoimmune diseases. Research has highlighted a potential role of autoantibodies in pathologic bone loss. The confounding effects of immunomodulatory drugs make it difficult to establish the contribution of autoantibodies amongst autoimmune disease sufferers. We attempted to examine the relationship between autoantibodies and bone mass in a population of 2812 elderly participants without clinical autoimmune disease. Serum samples were assayed for a panel of autoantibodies (anti-nuclear, extractable nuclear antigen, anti-neutrophil cytoplasmic, thyroid peroxidase, tissue transglutaminase, anti-cardiolipin, rheumatoid factor, and cyclic citrullinated peptide). Bone mass was measured using quantitative ultrasound (QUS) of the calcaneus. The relationship between each autoantibody and bone mass was determined using linear regression models. Anti-nuclear autoantibodies were the most prevalent, positive in approximately 11%, and borderline in roughly 23% of our sample. They were also the only autoantibody observed to be significantly associated with QUS index in the univariate analysis (n=1628; r=−0.20; 95% CI: −0.40–0.00; p=0.046). However, statistical significance was lost after adjustment for various other potential confounders. None of the other autoantibodies was associated with QUS index in either univariate or multivariate analysis. We are limited by the cross-sectional nature of the study and the low prevalence of autoantibodies in our nonclinical sample.
- Published
- 2018
- Full Text
- View/download PDF
21. Thyroid Antibodies, Autoimmunity and Cognitive Decline: Is There a Population-Based Link
- Author
-
Kate Napthali, Michael Boyle, Huy Tran, Peter W. Schofield, Roseanne Peel, Mark McEvoy, Christopher Oldmeadow, and John Attia
- Subjects
Dementia ,Hashimoto disease ,Encephalitis ,Autoantibodies ,Anti-nuclear antibodies ,Nuclear antigens ,Autoimmune thyroiditis ,Mild cognitive impairment ,Neurology. Diseases of the nervous system ,RC346-429 ,Geriatrics ,RC952-954.6 - Abstract
Background: Autoimmunity is considered an uncommon but under-recognised cause of cognitive decline. Methods: Serum samples from 3,253 randomly selected subjects enrolled in the Hunter Community Study, aged 55-85 years, were assayed for thyrotropin stimulatory hormone, anti-thyroid peroxidase antibodies (TPO-Ab), anti-nuclear antibodies (ANA) and extractable nuclear antigens (ENA). Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS) tool. Results: TPO-Ab were found in 8.4% and ANA in 27.9% of the study population, of whom 3% had positive ENA findings. No relationship was found between the ARCS score and either TPO-Ab (coefficient = 0.133; 95% CI -0.20, 0.82, p = 0.616), ANA at a low (coefficient = 1.01; 95% CI -2.58, 0.55, p = 0.203) or a high titre (coefficient = -0.65; 95% CI -2.59, 1.28, p = 0.508), or ENA antibodies (coefficient = 5.12; 95% CI -0.53, 10.77; p = 0.076). Conclusions: Autoantibody findings are common in an aging population and are not associated with cognitive decline.
- Published
- 2014
- Full Text
- View/download PDF
22. Clinical and biochemical correlates of serum L-ergothioneine concentrations in community-dwelling middle-aged and older adults.
- Author
-
Salvatore Sotgia, Angelo Zinellu, Arduino A Mangoni, Gianfranco Pintus, John Attia, Ciriaco Carru, and Mark McEvoy
- Subjects
Medicine ,Science - Abstract
BackgroundDespite the increasing interest towards the biological role of L-ergothioneine, little is known about the serum concentrations of this unusual aminothiol in older adults. We addressed this issue in a representative sample of community-dwelling middle-aged and older adults.MethodsBody mass index, estimated glomerular filtration rate, serum concentrations of L-ergothioneine, taurine, homocysteine, cysteine, glutathione, cysteinylglycine, and glutamylcysteine were evaluated in 439 subjects (age 55-85 years) randomly selected from the Hunter Community Study.ResultsMedian L-ergothioneine concentration in the entire cohort was 1.01 IQR 0.78-1.33 µmol/L. Concentrations were not affected by gender (P = 0.41) or by presence of chronic medical conditions (P = 0.15). By considering only healthy subjects, we defined a reference interval for L-ergothioneine serum concentrations from 0.36 (90% CI 0.31-0.44) to 3.08 (90% CI 2.45-3.76) µmol/L. Using stepwise multiple linear regression analysis L-ergothioneine was negatively correlated with age (rpartial = -0.15; P = 0.0018) and with glutamylcysteine concentrations (rpartial = -0.13; P = 0.0063).ConclusionsA thorough analysis of serum L-ergothioneine concentrations was performed in a large group of community-dwelling middle-aged and older adults. Reference intervals were established. Age and glutamylcysteine were independently negatively associated with L-ergothioneine serum concentration.
- Published
- 2014
- Full Text
- View/download PDF
23. Is serum zinc associated with pancreatic beta cell function and insulin sensitivity in pre-diabetic and normal individuals? Findings from the Hunter Community Study.
- Author
-
Khanrin P Vashum, Mark McEvoy, Abul Hasnat Milton, Md Rafiqul Islam, Stephen Hancock, and John Attia
- Subjects
Medicine ,Science - Abstract
AIM: To determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and insulin sensitivity in the former 2 groups. METHOD: Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator. RESULT: A total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p
- Published
- 2014
- Full Text
- View/download PDF
24. Fasting whole blood fatty acid profile and risk of type 2 diabetes in adults: a nested case control study.
- Author
-
Amani Alhazmi, Elizabeth Stojanovski, Manohar L Garg, and Mark McEvoy
- Subjects
Medicine ,Science - Abstract
OBJECTIVE: to determine the association of fasting whole blood fatty acid concentrations with incidence of type 2 diabetes in adults. METHODS: A nested case-control study of 187 subjects from a cohort of men and women aged 55-85 years from the Hunter Region, New South Wales, Australia. Fasting whole blood fatty acids were measured using gas chromatography and incidence of type 2 diabetes was ascertained by self-reported questionnaire at the study follow-up. RESULTS: After adjustment for potential confounding variables, positive associations with type 2 diabetes were seen for dihomo-gamma-linolenic acid (DGLA) (OR = 1.04, 95% CI:1.01-1.07, P = 0.01); arachidonic acid (ARA) (OR = 1.01, 95% CI:1.00-1.01, P = 0.002); alpha-linolenic acid (ALA) (OR = 1.10, 95% CI: 1.03-1.18, P = 0.01); eicosapentaenoic acid (EPA) (OR = 1.05, 95% CI:1.02-1.08, P = 0.001); and docosahexaenoic acid (DHA) (OR = 1.03, 95% CI:1.02-1.05, P
- Published
- 2014
- Full Text
- View/download PDF
25. Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh.
- Author
-
Md Rafiqul Islam, Iqbal Arslan, John Attia, Mark McEvoy, Patrick McElduff, Ariful Basher, Waliur Rahman, Roseanne Peel, Ayesha Akhter, Shahnaz Akter, Khanrin P Vashum, and Abul Hasnat Milton
- Subjects
Medicine ,Science - Abstract
AimsTo determine serum zinc level and other relevant biological markers in normal, prediabetic and diabetic individuals and their association with Homeostasis Model Assessment (HOMA) parameters.MethodsThis cross-sectional study was conducted between March and December 2009. Any patient aged ≥ 30 years attending the medicine outpatient department of a medical university hospital in Dhaka, Bangladesh and who had a blood glucose level ordered by a physician was eligible to participate.ResultsA total of 280 participants were analysed. On fasting blood sugar results, 51% were normal, 13% had prediabetes and 36% had diabetes. Mean serum zinc level was lowest in prediabetic compared to normal and diabetic participants (mean differences were approximately 65 ppb/L and 33 ppb/L, respectively). In multiple linear regression, serum zinc level was found to be significantly lower in prediabetes than in those with normoglycemia. Beta cell function was significantly lower in prediabetes than normal participants. Adjusted linear regression for HOMA parameters did not show a statistically significant association between serum zinc level, beta cell function (P = 0.07) and insulin resistance (P = 0.08). Low serum zinc accentuated the increase in insulin resistance seen with increasing BMI.ConclusionParticipants with prediabetes have lower zinc levels than controls and zinc is significantly associated with beta cell function and insulin resistance. Further longitudinal population based studies are warranted and controlled trials would be valuable for establishing whether zinc supplementation in prediabetes could be a useful strategy in preventing progression to Type 2 diabetes.
- Published
- 2013
- Full Text
- View/download PDF
26. Transsulfuration pathway thiols and methylated arginines: the Hunter Community Study.
- Author
-
Arduino A Mangoni, Angelo Zinellu, Ciriaco Carru, John R Attia, and Mark McEvoy
- Subjects
Medicine ,Science - Abstract
Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity] and with symmetric dimethylarginine (SDMA). We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS), and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis) were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR) = 64 (60-70) years].REGRESSION ANALYSIS SHOWED THAT: a) age (P = 0.001), gender (P = 0.03), lower estimated glomerular filtration rate (eGFR, P = 0.08), body mass index (P = 0.008), treatment with beta-blockers (P = 0.03), homocysteine (P = 0.02), and glutamylcysteine (P = 0.003) were independently associated with higher ADMA concentrations; and b) age (P = 0.001), absence of diabetes (P = 0.001), lower body mass index (P = 0.01), lower eGFR (P
- Published
- 2013
- Full Text
- View/download PDF
27. Associations between three diet quality indices, genetic risk and body composition: A prospective cohort study
- Author
-
Katherine M. Livingstone, Catherine Milte, Steven J. Bowe, Rachel L. Duckham, Joey Ward, Michelle A. Keske, Mark McEvoy, Barbara Brayner, and Gavin Abbott
- Subjects
Adult ,Cohort Studies ,Absorptiometry, Photon ,Nutrition and Dietetics ,Bone Density ,Risk Factors ,Body Composition ,Humans ,Obesity ,Prospective Studies ,Diet, Mediterranean ,Critical Care and Intensive Care Medicine ,Body Mass Index - Abstract
Diet and genetic predisposition to adiposity are independent predictors of body composition, yet few cohort studies have examined the association between overall diet quality indices, genetic risk and body composition. This study examined the prospective association of three diet quality indices and a polygenic risk score (PRS) with trunk fat mass, total fat mass, lean mass and bone mineral content.Adults from UK Biobank cohort were included. Dietary intake was assessed using the Oxford WebQ and three diet quality indices calculated: Recommended Food Score (RFS); Mediterranean Diet Score (MDS); Healthy Diet Indicator (HDI). Bioimpedance data were available for trunk fat, total fat and lean mass (kg). Trunk fat mass (kg), total fat mass (kg) and lean mass (kg) were assessed using bioelectrical impedance (BIA) in 17,478 adults. Bone mineral content (g) was available from dual energy x-ray absorptiometry (DXA) scans in 11,887 participants. Linear regression analyses, adjusted for demographic and lifestyle confounders, were used to estimate prospective associations between each diet quality index and body composition outcomes. A PRS created from 97 adiposity-related single nucleotide polymorphisms was used to examine interaction effects.A total of 17,478 adults (M = 55.9, SD 7.5 years) were followed up for up to 10 years. RFS, HDI and MDS were inversely associated with trunk fat (RFS: B -0.29; 95% CI: -0.33, -0.25; HDI: -0.23; -0.27, -0.19; MDS: -0.22; -0.26, -0.18), total fat (RFS: B -0.49; 95% CI: -0.56, -0.42; HDI: -0.38; -0.45, -0.32; MDS: -0.38; -0.44, -0.32) and lean (RFS: B -0.10; 95% CI: -0.14, -0.06; HDI: -0.07; -0.11, -0.03; MDS: -0.07; -0.11, -0.04) mass. Diet quality was positively associated with bone mineral content (RFS: B 8.23; 95% CI: 2.14, 14.3; HDI: 6.77; 1.00, 12.5). There was evidence of non-linear associations between diet quality (RFS and HDI only) and trunk fat (p 0.01) and total fat mass (p 0.05). There was limited evidence PRS was associated with body composition, with interaction effects of PRS and HDI (p-interaction = 0.039) and MDS (p-interaction = 0.031) on total fat mass.Higher diet quality was associated with lower trunk fat, total fat and lean mass, regardless of the diet quality index examined (RFS, HDI or MDS), while higher diet quality (RFS and HDI only) was associated with higher bone mineral content. The benefit of higher diet quality on reducing total fat mass was most evident in individuals with higher generic risk of adiposity. These findings underscore the importance of a high-quality diet for maintaining optimal body composition, particularly in individuals with genetic pre-disposition to adiposity.
- Published
- 2022
- Full Text
- View/download PDF
28. Reply-Letter to the Editor-Associations between three diet quality indices, genetic risk and body composition: A prospective cohort study
- Author
-
Katherine M. Livingstone, Catherine Milte, Steven J. Bowe, Rachel L. Duckham, Joey Ward, Michelle A. Keske, Mark McEvoy, Barbara Brayner, and Gavin Abbott
- Subjects
Nutrition and Dietetics ,Critical Care and Intensive Care Medicine - Published
- 2023
- Full Text
- View/download PDF
29. Using the AUSDRISK score to screen for pre‐diabetes and diabetes in GP practices: a case‐finding approach
- Author
-
Roseanne Peel, Martha Parsons, John Wiggers, Natasha Weaver, Alexis J. Hure, Samir Samman, John Attia, Judy Luu, Ranil Jayawardena, Kerry Fleming, Mark McEvoy, Chris Rissel, Priyanga Ranasinghe, Shamasunder Acharya, and Elizabeth G. Holliday
- Subjects
Adult ,Blood Glucose ,medicine.medical_specialty ,Receiver operating characteristic ,business.industry ,Public Health, Environmental and Occupational Health ,medicine.disease ,Sensitivity and Specificity ,Prediabetic State ,Diabetes Mellitus, Type 2 ,Pre diabetes ,Hba1c test ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Mass Screening ,Case finding ,Prediabetes ,business ,Cut-point ,Point of care - Abstract
OBJECTIVE To identify the optimal AUSDRISK threshold score to screen for pre-diabetes and diabetes. METHODS A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre-diabetes (5.7-6.4% or 39-47 mmol/mol), or normal (
- Published
- 2022
- Full Text
- View/download PDF
30. Generation of cardio-protective antibodies after pneumococcal polysaccharide vaccine: Early results from a randomised controlled trial
- Author
-
Shu Ren, Philip M. Hansbro, Wichat Srikusalanukul, Jay C. Horvat, Tegan Hunter, Alexandra C. Brown, Roseanne Peel, Jack Faulkner, Tiffany-Jane Evans, Shu Chuen Li, David Newby, Alexis Hure, Walter P. Abhayaratna, Sotirios Tsimikas, Ayelet Gonen, Joseph L. Witztum, John Attia, Walter Abhayaratna, Catherine D'Este, Andrew Tonkin, Ingrid Hopper, Amanda Thrift, Christopher Levi, Jonathan Sturm, David Durrheim, Joseph Hung, Tom Briffa, Derek Chew, Phil Anderson, Lynelle Moon, and Mark McEvoy
- Subjects
Pneumococcal Vaccines ,Streptococcus pneumoniae ,Immunoglobulin M ,Immunoglobulin G ,Australia ,Humans ,Atherosclerosis ,Cardiology and Cardiovascular Medicine ,Biomarkers - Abstract
Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years.A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH).Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up.PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events.
- Published
- 2022
- Full Text
- View/download PDF
31. Data from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
- Author
-
Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
- Abstract
Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist–hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls.Methods: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable.Results: The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10−17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89–2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44–1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10–1.39; P = 5.3 × 10−4). There was evidence of directional pleiotropy (P = 1.5 × 10−4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10−4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS.Conclusions: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI.Impact: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503–10. ©2016 AACR.
- Published
- 2023
- Full Text
- View/download PDF
32. Supplemental Table 2. Average BMIs in the ANECS, SEARCH and iCOGS endometrial cancer datasets. from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
- Author
-
Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
- Abstract
Excel file detailing average BMI per study population
- Published
- 2023
- Full Text
- View/download PDF
33. Supplemental Table 1. Details of cases and controls included in the endometrial cancer analyses from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
- Author
-
Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
- Abstract
Excel file detailing case-control populations
- Published
- 2023
- Full Text
- View/download PDF
34. Supplementary Table 3: Association of 77 body mass index (BMI) SNPs with endometrial cancer risk and BMI in the endometrial cancer dataset from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
- Author
-
Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
- Abstract
Excel file detailing single BMI SNP associations with EC risk and BMI
- Published
- 2023
- Full Text
- View/download PDF
35. Supplementary Table 4. Association of 47 waist-hip ratio (WHR) SNPs with endometrial cancer risk from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
- Author
-
Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
- Abstract
Excel file detailing single WHR SNP associations with EC risk
- Published
- 2023
- Full Text
- View/download PDF
36. Supplementary Text for: Genetic risk score Mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
- Author
-
Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
- Abstract
Supplementary Text for manuscript.
- Published
- 2023
- Full Text
- View/download PDF
37. An Historical Introduction to the Philosophy of Mathematics: A Reader
- Author
-
Russell Marcus, Mark McEvoy
- Published
- 2016
38. Causal tracking reliabilism and the Gettier problem.
- Author
-
Mark McEvoy
- Published
- 2014
- Full Text
- View/download PDF
39. Serum L‐arginine and endogenous methylarginine concentrations predict irritable bowel syndrome in adults: A nested case‐control study
- Author
-
Arduino A. Mangoni, Nicholas J. Talley, Marjorie M. Walker, Wayne Smith, Christopher Oldmeadow, Roseanne Peel, Mark McEvoy, Stephen Hancock, Elizabeth G. Holliday, and John Attia
- Subjects
Male ,medicine.medical_specialty ,Methylarginine ,Arginine ,Nitric Oxide ,Psychological Distress ,Gastroenterology ,Nitric oxide ,Cohort Studies ,Neurogastroenterology ,chemistry.chemical_compound ,L‐arginine ,Internal medicine ,Odds Ratio ,medicine ,Humans ,older adults ,Irritable bowel syndrome ,Aged ,Aged, 80 and over ,irritable bowel syndrome ,business.industry ,Odds ratio ,Middle Aged ,methylarginine ,medicine.disease ,Logistic Models ,ROC Curve ,Oncology ,chemistry ,Case-Control Studies ,Nested case-control study ,Cohort ,Female ,Original Article ,business ,Asymmetric dimethylarginine ,Biomarkers - Abstract
BACKGROUND AIMS: Nitric oxide, a major inhibitory nonadrenergic, noncholinergic neurotransmitter that relaxes smooth muscle, may be implicated in the pathophysiology of visceral hypersensitivity in irritable bowel syndrome (IBS). Impaired bioavailability of the nitric oxide precursor molecule L-arginine and higher concentrations of methylarginines (endogenous inhibitors of nitric oxide synthesis) are known to impair nitric oxide synthesis in numerous gastrointestinal cell types. We therefore examined serum concentrations of L-arginine and the methylarginines in a nested case-control study, to assess whether these factors are associated with adult IBS.Data on clinical characteristics, methylarginines, and L-arginine (measured using LC-MS/MS) were collected from a random population-based cohort of Australian adults (median age = 64 years; IQR = 60-70). Cases of IBS, defined according to Rome III criteria (N = 156), and controls (N = 332) were identified from within the cohort at the 5-year follow-up.In adjusted logistic regression analyses, L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine/asymmetric dimethylarginine ratio, and Kessler-10 psychological distress scores were significantly associated with IBS (p 0.05). [Correction added on 18 September 2021, after first online publication: In the preceding sentence, the value (p 0.05) has been changed to (p 0.05)]. Similar results were found for IBS subtypes. Higher serum L-arginine concentration had the strongest association with IBS diagnosis, with an odds ratio of 9.03 for those with serum L-arginine at the 75th (84 μmol/L) versus 25th (46 μmol/L) percentile (95% CI: 5.99-13.62). L-arginine had the best discriminative ability with a bias-adjusted area under the receiver operator characteristic curve of 0.859.Higher serum concentrations of L-arginine and endogenous methylarginines are strongly associated with IBS in adults.
- Published
- 2021
- Full Text
- View/download PDF
40. Irritable bowel syndrome and risk of glaucoma: An analysis of two independent population‐based cohort studies
- Author
-
Ian C. Francis, Henrik Toft Sørensen, Nicholas J. Talley, Sven Pettersson, Jae H. Kang, Mark McEvoy, Andrew White, Minas T. Coroneo, Ashish Agar, Erzsébet Horváth-Puhó, Zachary E. McPherson, and Louis R. Pasquale
- Subjects
Adult ,Male ,medicine.medical_specialty ,genetic structures ,Denmark ,medicine.medical_treatment ,General Population Cohort ,Glaucoma ,Neurogastroenterology ,cohort studies ,Risk Factors ,Internal medicine ,medicine ,Glaucoma surgery ,Humans ,Prospective Studies ,Risk factor ,Prospective cohort study ,Aged ,Aged, 80 and over ,irritable bowel syndrome ,Glaucoma medication ,business.industry ,Incidence ,Gastroenterology ,Odds ratio ,Middle Aged ,medicine.disease ,United Kingdom ,eye diseases ,glaucoma ,risk factor ,Oncology ,Female ,Original Article ,business ,Cohort study - Abstract
OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome-host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma.DESIGN: Two prospective cohort studies.SUBJECTS: The 1958 United Kingdom Birth Cohort (UKBC; 9091 individuals) and the Danish National Registry of Patients (DNRP; 62,541 individuals with IBS and 625,410 matched general population cohort members).METHODS: In the UKBC, participants were surveyed throughout life (including at ages 42 and 50). The DNRP contains records of hospital-based contacts and prescription data from the national prescription database.MAIN OUTCOME MEASURE: The main outcome measure was incidence of glaucoma. In the UKBC, incident glaucoma at age 50 (n = 48) was determined through comparison of survey responses at ages 42 and 50 years. In the DNRP, glaucoma was assessed by hospital diagnosis (n = 1510), glaucoma surgery (n = 582) and initiation of glaucoma medications (n = 1674).RESULTS: In the UKBC, the odds ratio (OR) of developing glaucoma between ages 42 and 50 in persons with a chronic IBS diagnosis was increased [OR: 5.84, 95% confidence interval (CI): 2.26-15.13]. People with an IBS diagnosis in the DNRP had a hazard ratio (HR) of 1.35 for developing physician-diagnosed glaucoma (95% CI: 1.16-1.56), an HR of 1.35 for undergoing glaucoma surgery (95% CI: 1.06-1.70) and an HR of 1.19 for initiating glaucoma medication (95% CI: 1.03-1.38).CONCLUSIONS: In two large European cohort studies, IBS is a risk factor for glaucoma.
- Published
- 2021
- Full Text
- View/download PDF
41. Overweight or Obesity increases the risk of cardiovascular disease among older Australian adults, even in the absence of cardiometabolic risk factors: A Bayesian survival analysis from the Hunter Community Study
- Author
-
Jacob Opio, Katie Wynne, John Attia, Stephen Hancock, Christopher Oldmeadow, Brian Kelly, Kerry Inder, and Mark McEvoy
- Subjects
Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) - Abstract
Objective To estimate the risk of cardiovascular disease (CVD) in older adults with overweight or obesity without metabolic risk factors using a Bayesian survival analysis. Design: Prospective cohort study with median follow-up of 9.7 years. Setting: Newcastle, New South Wales, Australia. Participants : A total of 2313 community-dwelling older men and women. Intervention/exposure: Participants without known CVD and with a body mass index (BMI) ≥ 18.5 kgm2 were stratified by BMI and metabolic risk to create six BMI-metabolic health categories. Metabolic risk was defined according to the International Diabetes Federation criteria for metabolic syndrome. “Metabolically healthy” was defined as absence of metabolic risk factors. Bayesian survival analysis, incorporating prior information from a previously published meta-analysis was used to assess the effect of BMI-metabolic health categories on time from recruitment to CVD. Main Outcome: Incident physician-diagnosed CVD, defined as fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, angina, or coronary revascularisation procedure, was determined by linkage to hospital admissions records and Medicare Australia data. Secondary outcomes were cardiovascular mortality and all-cause mortality. Results From 2313 adults with complete metabolic health data over a median follow-up of 9.7 years, 283 incident CVD events, 58 CVD related deaths and 277 deaths from any cause occurred. In an adjusted Bayesian survival model of complete cases with informative prior and metabolically healthy normal weight as the reference group, the risk of CVD was increased in metabolically healthy overweight (HR = 1.52, 95% credible interval 0.96–2.36), and in metabolically healthy obesity (HR = 1.86, 95% credible interval 1.14–3.08). Imputation of missing metabolic health and confounding data did not change the results. Conclusion There was increased risk of CVD in older adults with overweight or obesity, even in the absence of any metabolic abnormality. This argues against the notion of “metabolically healthy” overweight or obesity.
- Published
- 2022
- Full Text
- View/download PDF
42. Experimental mathematics, computers and the a priori.
- Author
-
Mark McEvoy
- Published
- 2013
- Full Text
- View/download PDF
43. Factors to consider during the implementation of nutrition and physical activity trials for people with psychotic illness into an Australian community setting
- Author
-
Mary-Claire Hanlon, Mark McEvoy, Doreen Mucheru, Lesley MacDonald-Wicks, and Samantha Ashby
- Subjects
Adult ,Health Personnel ,Psychological intervention ,Nutritional Status ,Health informatics ,Health Services Accessibility ,Knowledge translation ,Health administration ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Psychotic illness ,Medicine ,Humans ,030212 general & internal medicine ,Exercise ,Life Style ,Lifestyle interventions ,Qualitative Research ,Medical education ,Clinical Trials as Topic ,business.industry ,Health Policy ,Nursing research ,Mental Disorders ,lcsh:Public aspects of medicine ,Attendance ,Australia ,lcsh:RA1-1270 ,Mental illness ,medicine.disease ,Mental health ,Community Mental Health Services ,030227 psychiatry ,Community managed organisations ,Health Services Research ,business ,Research Article - Abstract
Background Research in lifestyle interventions focusing on nutrition and physical activity in people living with psychotic illness, highlights anthropometric and metabolic benefits of these interventions. However, little is known about potential factors to consider during implementation into real-world contexts. Community-managed organisations (CMOs) that provide services for people with mental illness, offer an ideal implementation context for lifestyle interventions. Successful translation of lifestyle interventions into CMOs may be achieved though considering the factors associated with program access and delivery in these settings. This study primarily aimed to identify the factors that affect program access in a local CMO from the perspective of consumers and staff. The secondary aim was to describe the elements that impact on program delivery from the perspective of staff. Methods Thirteen semi-structured interviews were conducted with 6 consumers and 7 staff in a CMO in regional Australia. Topics explored in interviews were based on implementation concepts identified in the “Integrated Promoting Action on Research Implementation in Health Systems” (i-PARIHS) knowledge translation framework. Thematic data analysis was conducted using Nvivo software. Results Emergent themes on issues that influenced program access were (1) consumer financial status, domestic responsibilities, and health; (2) the design and delivery of programs; (3) structure and practices of the organisation; (4) attitude, skills and effort of staff involved in program delivery; and (5) social connections and stigma experienced by consumers during program access. Moreover, staff perceptions on elements that impacted program delivery highlighted themes on consumer attendance and interest in prospective programs, availability and restrictions to the use of funding, as well as the organisational structure and practices. Conclusions The factors affecting program access and delivery can generally be managed or planned for during the design of lifestyle interventions and subsequent translation into the CMO context. However, resolution of issues related to consumer financial status and health requires the collaboration of various government sectors for system-wide solutions.
- Published
- 2020
- Full Text
- View/download PDF
44. Daily steps and diet, but not sleep, are related to mortality in older Australians
- Author
-
Elizabeth G. Holliday, Mark McEvoy, John Attia, Clare E. Collins, Philip J. Morgan, Mitch J. Duncan, Benjamin Ewald, Stina Oftedal, Ronald C. Plotnikoff, Emmanuel Stamatakis, Nick Glozier, Wendy J. Brown, and Corneel Vandelanotte
- Subjects
Male ,Physical activity ,Physical Therapy, Sports Therapy and Rehabilitation ,Fitness Trackers ,Walking ,Older population ,03 medical and health sciences ,0302 clinical medicine ,Insomnia ,medicine ,Humans ,Orthopedics and Sports Medicine ,Prospective Studies ,030212 general & internal medicine ,Mortality ,Prospective cohort study ,Aged ,business.industry ,Australia ,030229 sport sciences ,Middle Aged ,Sleep in non-human animals ,Diet ,Ageing ,Pedometer ,Household income ,Female ,New South Wales ,medicine.symptom ,Sleep ,business ,Demography - Abstract
Objectives Supporting healthy ageing is a key priority worldwide. Physical activity, diet quality and sleep are all associated with health outcomes, but few studies have explored their independent associations with all-cause mortality in an older population in the same model. The study aim was to examine associations between step-count, self-reported diet quality, restless sleep, and all-cause mortality in adults aged 55–85 years. Design A prospective cohort study of adults in Newcastle, New South Wales, Australia. Method Data were from 1697 participants (49.3% women; baseline mean age 65.4 ± 7.1 years). Daily steps (measured by pedometer), diet quality (from a modified Australian Recommended Food Score), and frequency of restless sleep (by self-report) were assessed in relation to all-cause mortality using Cox proportional hazard regression with adjustment for sex, age, household income and smoking. Baseline data were collected between January 2005 and April 2008, and last follow-up was in March 2017 (median follow-up 9.6 years). Results Higher step count (HR: 0.93, 95%CI: 0.88–0.98 per 1000-step increment) and higher diet quality (HR: 0.86, 95%CI: 0.74–0.99 per 8-point increment in diet quality score) were associated with reduced mortality risk. Restless sleep for ≥3 nights/week was not associated with mortality risk (HR: 1.03, 95%CI: 0.78–1.39). Sensitivity analyses, adjusting for chronic disease and excluding deaths Conclusions Increased daily steps and consumption of a greater variety of nutrient-dense foods every week would result in substantial health benefits for older people. Future research should include a greater variety of sleep measures.
- Published
- 2020
- Full Text
- View/download PDF
45. The effect of zinc supplementation on glucose homeostasis: a randomised double-blind placebo-controlled trial
- Author
-
John R. Attia, Elizabeth Holliday, Natasha Weaver, Roseanne Peel, Kerry C. Fleming, Alexis Hure, John Wiggers, Mark McEvoy, Andrew Searles, Penny Reeves, Priyanga Ranasinghe, Ranil Jayawardena, Samir Samman, Judy Luu, Chris Rissel, and Shamasunder Acharya
- Subjects
Blood Glucose ,Glycated Hemoglobin ,Endocrinology, Diabetes and Metabolism ,Australia ,General Medicine ,Prediabetic State ,Zinc ,Endocrinology ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,Dietary Supplements ,Internal Medicine ,Homeostasis ,Humans ,Female ,Uncategorized - Abstract
Aims The burden and health costs of Type 2 Diabetes Mellitus continue to increase globally and prevention strategies in at-risk people need to be explored. Previous work, in both animal models and humans, supports the role of zinc in improving glucose homeostasis. We, therefore, aimed to test the effectiveness of zinc supplementation on glycaemic control in pre-diabetic adults. Methods We conducted a randomized, double-blind, placebo-controlled trial across 10 General Practitioner (GP) practices in NSW, Australia. The trial is known as Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD)Study. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7–6.4%, 39–46 mmol/mol) men and women (N = 98) were all assigned to a free state government telephone health coaching service (New South Wales Get Healthy Information and Coaching Service) and then randomised to either daily 30 mg zinc gluconate or placebo. Blood tests were collected at baseline, 1, 6 and 12 months for the primary outcomes (HbA1c, fasting blood glucose (FBG)); secondary outcomes included Homeostasis Model Assessment 2 (HOMA 2) parameters, lipids, body weight, height, waist circumference, blood pressure and pulse. Results The baseline-adjusted mean group difference at 6 months, expressed as treatment–placebo, (95% CI) was −0.02 (−0.14, 0.11, p = 0.78) for HbA1c and 0.17 (−0.07, 0.42; p = 0.17) for FBG, neither of which were statistically significant. There were also no significant differences between groups in any of the secondary outcomes. Zinc was well tolerated, and compliance was high (88%). Conclusion We believe our results are consistent with other Western clinical trial studies and do not support the use of supplemental zinc in populations with a Western diet. There may still be a role for supplemental zinc in the developing world where diets may be zinc deficient. Trial registration Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.
- Published
- 2022
- Full Text
- View/download PDF
46. Revisiting ‘The New 4CT Problem’
- Author
-
Mark McEvoy
- Published
- 2022
- Full Text
- View/download PDF
47. Multi-trait genome-wide association study of opioid addiction:OPRM1and Beyond
- Author
-
Nicholas G. Martin, Louisa Degenhardt, Emma C. Johnson, Bernice Porjesz, Linran Zhou, Dieter B. Wildenauer, Erin Kelty, Nathan C. Gaddis, Rodney J. Scott, Bryan C. Quach, Tatiana Foroud, Alex Waldrop, Brion S. Maher, Ravi Mathur, Joel Gelernter, Matthew Randesi, Sibylle G. Schwab, Laura J. Bierut, Dana B. Hancock, Gary K. Hulse, Henry R. Kranzler, Mark McEvoy, Miriam Adelson, Leah Wetherill, Orna Levran, Jesse Marks, Hang Zhou, Elizabeth G. Holliday, Elliot C. Nelson, Bradley Todd Webb, Richard C. Crist, Dongbing Lai, Howard J. Edenberg, Mary Jeanne Kreek, Kathleen K. Bucholz, Paul W. Jeffries, Wade H Berrettini, Eric O. Johnson, Arpana Agrawal, Grant W. Montgomery, John Attia, and Richard Gruza
- Subjects
Genetics ,Addiction ,media_common.quotation_subject ,SNP ,Genome-wide association study ,Genomics ,Biology ,Heritability ,Phenotype ,Opioid addiction ,Gene ,media_common - Abstract
Opioid addiction (OA) has strong heritability, yet few genetic variant associations have been robustly identified. Only rs1799971, the A118G variant inOPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data and published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg> 0.9). We observed the strongest evidence to date forOPRM1: lead SNP rs9478500 (p=2.56×10−9). Gene-based analyses identified novel genome-wide significant associations withPPP6CandFURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
- Published
- 2021
- Full Text
- View/download PDF
48. Genetic analyses of gynecological disease identify genetic relationships between uterine fibroids and endometrial cancer, and a novel endometrial cancer genetic risk region at the WNT4 1p36.12 locus
- Author
-
Tracy O'Mara, Maxine Chen, Sally-Anne Mortlock, Dale Nyholt, Stuart MacGregor, Leanne WALLACE, Montserrat Garcia-Closas, Jolanta Lissowska, Krina Zondervan, Mark McEvoy, Peter Rogers, and Mette Nyegaard
- Subjects
Oncology ,medicine.medical_specialty ,Uterine fibroids ,Endometriosis ,Biology ,Neoplasm Proteins/genetics ,Uterine cancer ,Internal medicine ,Genetics ,medicine ,Humans ,Risk factor ,Genetics (clinical) ,Polycystic Ovary Syndrome/genetics ,Endometrial cancer ,Cancer ,Mendelian Randomization Analysis ,medicine.disease ,Leiomyoma/genetics ,Polycystic ovary ,female genital diseases and pregnancy complications ,Leiomyoma ,Genetic Loci ,Female ,Wnt4 Protein/genetics ,Endometrial Neoplasms/genetics ,Endometriosis/genetics ,Genome-Wide Association Study - Abstract
Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-cancerous gynecological diseases and endometrial cancer risk by assessing genetic correlation, causal relationships and shared risk loci. We found significant genetic correlation between endometrial cancer and PCOS, and uterine fibroids. Adjustment for genetically predicted body mass index (a risk factor for PCOS, uterine fibroids and endometrial cancer) substantially attenuated the genetic correlation between endometrial cancer and PCOS but did not affect the correlation with uterine fibroids. Mendelian randomization analyses suggested a causal relationship between only uterine fibroids and endometrial cancer. Gene-based analyses revealed risk regions shared between endometrial cancer and endometriosis, and uterine fibroids. Multi-trait GWAS analysis of endometrial cancer and the genetically correlated gynecological diseases identified a novel genome-wide significant endometrial cancer risk locus at 1p36.12, which replicated in an independent endometrial cancer dataset. Interrogation of functional genomic data at 1p36.12 revealed biologically relevant genes, including WNT4 which is necessary for the development of the female reproductive system. In summary, our study provides genetic evidence for a causal relationship between uterine fibroids and endometrial cancer. It further provides evidence that the comorbidity of endometrial cancer, PCOS and uterine fibroids may partly be due to shared genetic architecture. Notably, this shared architecture has revealed a novel genome-wide risk locus for endometrial cancer.
- Published
- 2021
- Full Text
- View/download PDF
49. The Apolipoprotein Allele and Sensorineural Hearing Loss in Older Community-Dwelling Adults in Australia
- Author
-
John Attia, Mark McEvoy, Steven J. Bowe, and Julia Z. Sarant
- Subjects
Apolipoprotein E ,medicine.medical_specialty ,Genotype ,Hearing loss ,Hearing Loss, Sensorineural ,Population ,Audiology ,01 natural sciences ,03 medical and health sciences ,Speech and Hearing ,0302 clinical medicine ,0103 physical sciences ,otorhinolaryngologic diseases ,Humans ,Medicine ,Allele ,Cognitive decline ,030223 otorhinolaryngology ,education ,010301 acoustics ,Allele frequency ,Alleles ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Australia ,Middle Aged ,medicine.disease ,Apolipoproteins ,Cross-Sectional Studies ,Otorhinolaryngology ,Sample size determination ,Sensorineural hearing loss ,Independent Living ,medicine.symptom ,business - Abstract
OBJECTIVES: Previous research has investigated whether the apolipoprotein E (APOE) e4 allele, which is associated with an increased risk of cognitive decline, is also associated with hearing loss in older people. Results of the very limited research to date are conflicting, and sample sizes for all but one study were small. The present study aimed to investigate whether there is an association between the APOE e4 allele and hearing loss in a large, population-based sample of community-dwelling older adults. DESIGN: Cross-sectional audiometric data on hearing levels and APOE genotypes for 2006 participants (aged 55 to 85 years) of the Hunter Community Study were analyzed using multiple linear regression to examine the association between APOE e4 carrier status and the 4-frequency pure-tone average (0.5 to 4 kHz) in the better hearing ear, and also across individual frequencies in the better ear. RESULTS: Observed and expected APOE allele frequency distributions did not differ significantly overall from established general population allele frequency distributions. Unadjusted modeling using better ear pure-tone average showed a statistically significant association between APOE e4 allele status (0, 1, 2 copies) and reduced hearing loss, but when the model was adjusted for age, this was no longer statistically significant. Across individual hearing frequencies, unadjusted regression modeling showed APOE e4 status was significantly associated with a reduction in mean hearing thresholds at 1 and 2 kHz, but again this effect was no longer statistically significant after adjusting for age. CONCLUSIONS: The results of this study did not provide any evidence of a statistically significant association between APOE e4 allele status and hearing loss for older adults. Further investigation of the effect of homozygous carrier status on hearing thresholds is required.
- Published
- 2019
- Full Text
- View/download PDF
50. The efficacy of antibiotic treatment versus surgical treatment of uncomplicated acute appendicitis: Systematic review and network meta-analysis of randomized controlled trial
- Author
-
Napaphat Poprom, Mark McEvoy, Ammarin Thakkinstian, Chumpon Wilasrusmee, Pawin Numthavaj, John Attia, and Sasivimol Rattanasiri
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Antibiotics ,MEDLINE ,030230 surgery ,Lower risk ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Appendectomy ,Humans ,Uncomplicated appendicitis ,Randomized Controlled Trials as Topic ,business.industry ,General Medicine ,Appendicitis ,medicine.disease ,Anti-Bacterial Agents ,030220 oncology & carcinogenesis ,Meta-analysis ,Surgery ,business ,Complication - Abstract
Background The efficacy of antibiotics in appendicitis remains controversial, and physicians are not confident in prescribing antibiotics as the first line treatment. This network meta-analysis was conducted to assess the efficacy and safety of individual antibiotics in uncomplicated appendicitis. Methods Randomized controlled trials (RCTs) were identified from MEDLINE and SCOPUS databases since inception to July 2017. Studies. Network meta-analysis was applied to estimate treatment effects and safety. Probability of being the best treatment was estimated using surface under the cumulative ranking curve (SUCRA). Results Among 9 RCTs meeting our inclusion criteria. A network meta-analysis indicated that those receiving antibiotics had about 12–32% lower chance of treatment success and lower risk of complication about 23–86%, especially Beta-lactamase than appendectomy. The overall appendicitis recurrence rate in the antibiotic group was about 18.2%. The SUCRA indicated that appendectomy was ranked first for treatment success and least complications, followed by Beta-lactamase. Conclusions Appendectomy is still the most effective treatment in uncomplicated appendicitis but it carries complications. Beta-lactamase, might be an alternative treatment if there are any contraindications for operation.
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.