1,107 results on '"Graham CA"'
Search Results
2. Outcome after implementation of sepsis guideline in the emergency department of a university hospital in Hong Kong
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Yang, MLC, Graham, CA, and Rainer, TH
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- 2015
3. Could C-reactive protein be a potential biomarker of complicated acute appendicitis?
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Lai, CY, Leung, YK, and Graham, CA
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- 2014
4. Emergency physicians' preparedness for CBRNE incidents in Hong Kong
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Hung, KKC, Lam, ECC, Wong, MCS, Chan, EYY, Graham, CA, and Wong, TW
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- 2013
5. Children's discomfort during noninvasive cardiac output monitoring by suprasternal ultrasonographic transducer
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Chan, SSW, Cattermole, GN, Leung, MPY, Ho, GYL, Graham, CA, and Rainer, TH
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- 2013
6. Management of Suspected Deep Venous Thrombosis in an Emergency Medicine Ward in Hong Kong
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Hung, KKC, Graham, CA, Yim, WT, Yam, ESF, Cheung, NK, and Rainer, TH
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- 2011
7. Full Text Publication Rates of Studies Presented at an Asian Emergency Medicine Scientific Meeting
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Tan, PCF and Graham, CA
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- 2010
8. Making emergency medicine in Hong Kong sustainable
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Graham, CA
- Published
- 2016
9. Circulating human leucine-rich α-2-glycoprotein 1 mRNA and protein levels to detect acute appendicitis in patients with acute abdominal pain
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Rainer, TH, Leung, LY, Chan, CPY, Leung, YK, Cheng, NM, Lai, PBS, Cheung, YS, and Graham, CA
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- 2017
- Full Text
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10. “IT’S JUST A LITTLE BIT OF ADD-ON TO THE END, YOU KNOW” INTEGRATING JOINT PAIN, ANXIETY AND DEPRESSION IN PRIMARY CARE LONG-TERM CONDITION REVIEWS : ANALYSIS OF AUDIO-RECORDED CONSULTATIONS
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Jinks, C, Liddle, J, Healey, EL, Mallen, CD, and Chew-Graham, CA
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- 2016
11. Acceptability of a behavioural intervention to mitigate the psychological impacts of COVID-19 restrictions in older people with long-term conditions: a qualitative study
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Shearsmith, L, primary, Coventry, PA, additional, Sloan, C, additional, Henry, A, additional, Newbronner, E, additional, Littlewood, E, additional, Bailey, D, additional, Gascoyne, S., additional, Burke, L., additional, Ryde, E., additional, Woodhouse, R, additional, McMillan, D, additional, Ekers, D, additional, Gilbody, S, additional, and Chew-Graham, CA, additional
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- 2022
- Full Text
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12. Painful sex (dyspareunia) in women: prevalence and associated factors in a British population probability survey
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Mitchell, KR, Geary, R, Graham, CA, Datta, J, Wellings, K, Sonnenberg, P, Field, N, Nunns, D, Bancroft, J, Jones, KG, Johnson, AM, and Mercer, CH
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- 2017
- Full Text
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13. How the RCGP Research Paper of the Year 2020 reflects our motto 'Cum Scientia Caritas'
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Gronlund, T, Khan, N, and Chew-Graham, CA
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R1 - Abstract
'Editorial Material'
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- 2021
14. 'Reluctant pioneer': a qualitative study of doctors' experiences as patients with long COVID (vol 24, pg 833, 2021)
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Taylor, AK, Kingstone, T, Briggs, TA, O'Donnell, CA, Atherton, H, Blane, DN, and Chew-Graham, CA
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R1 - Published
- 2021
15. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
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Zhishan Chen, Xingyi Guo, Ran Tao, Jeroen R. Huyghe, Philip J. Law, Ceres Fernandez-Rozadilla, Jie Ping, Guochong Jia, Jirong Long, Chao Li, Quanhu Shen, Yuhan Xie, Maria N. Timofeeva, Minta Thomas, Stephanie L. Schmit, Virginia Díez-Obrero, Matthew Devall, Ferran Moratalla-Navarro, Juan Fernandez-Tajes, Claire Palles, Kitty Sherwood, Sarah E. W. Briggs, Victoria Svinti, Kevin Donnelly, Susan M. Farrington, James Blackmur, Peter G. Vaughan-Shaw, Xiao-Ou Shu, Yingchang Lu, Peter Broderick, James Studd, Tabitha A. Harrison, David V. Conti, Fredrick R. Schumacher, Marilena Melas, Gad Rennert, Mireia Obón-Santacana, Vicente Martín-Sánchez, Jae Hwan Oh, Jeongseon Kim, Sun Ha Jee, Keum Ji Jung, Sun-Seog Kweon, Min-Ho Shin, Aesun Shin, Yoon-Ok Ahn, Dong-Hyun Kim, Isao Oze, Wanqing Wen, Keitaro Matsuo, Koichi Matsuda, Chizu Tanikawa, Zefang Ren, Yu-Tang Gao, Wei-Hua Jia, John L. Hopper, Mark A. Jenkins, Aung Ko Win, Rish K. Pai, Jane C. Figueiredo, Robert W. Haile, Steven Gallinger, Michael O. Woods, Polly A. Newcomb, David Duggan, Jeremy P. Cheadle, Richard Kaplan, Rachel Kerr, David Kerr, Iva Kirac, Jan Böhm, Jukka-Pekka Mecklin, Pekka Jousilahti, Paul Knekt, Lauri A. Aaltonen, Harri Rissanen, Eero Pukkala, Johan G. Eriksson, Tatiana Cajuso, Ulrika Hänninen, Johanna Kondelin, Kimmo Palin, Tomas Tanskanen, Laura Renkonen-Sinisalo, Satu Männistö, Demetrius Albanes, Stephanie J. Weinstein, Edward Ruiz-Narvaez, Julie R. Palmer, Daniel D. Buchanan, Elizabeth A. Platz, Kala Visvanathan, Cornelia M. Ulrich, Erin Siegel, Stefanie Brezina, Andrea Gsur, Peter T. Campbell, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Martha L. Slattery, John D. Potter, Kostas K. Tsilidis, Matthias B. Schulze, Marc J. Gunter, Neil Murphy, Antoni Castells, Sergi Castellví-Bel, Leticia Moreira, Volker Arndt, Anna Shcherbina, D. Timothy Bishop, Graham G. Giles, Melissa C. Southey, Gregory E. Idos, Kevin J. McDonnell, Zomoroda Abu-Ful, Joel K. Greenson, Katerina Shulman, Flavio Lejbkowicz, Kenneth Offit, Yu-Ru Su, Robert Steinfelder, Temitope O. Keku, Bethany van Guelpen, Thomas J. Hudson, Heather Hampel, Rachel Pearlman, Sonja I. Berndt, Richard B. Hayes, Marie Elena Martinez, Sushma S. Thomas, Paul D. P. Pharoah, Susanna C. Larsson, Yun Yen, Heinz-Josef Lenz, Emily White, Li Li, Kimberly F. Doheny, Elizabeth Pugh, Tameka Shelford, Andrew T. Chan, Marcia Cruz-Correa, Annika Lindblom, David J. Hunter, Amit D. Joshi, Clemens Schafmayer, Peter C. Scacheri, Anshul Kundaje, Robert E. Schoen, Jochen Hampe, Zsofia K. Stadler, Pavel Vodicka, Ludmila Vodickova, Veronika Vymetalkova, Christopher K. Edlund, W. James Gauderman, David Shibata, Amanda Toland, Sanford Markowitz, Andre Kim, Stephen J. Chanock, Franzel van Duijnhoven, Edith J. M. Feskens, Lori C. Sakoda, Manuela Gago-Dominguez, Alicja Wolk, Barbara Pardini, Liesel M. FitzGerald, Soo Chin Lee, Shuji Ogino, Stephanie A. Bien, Charles Kooperberg, Christopher I. Li, Yi Lin, Ross Prentice, Conghui Qu, Stéphane Bézieau, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Loic Le Marchand, Anna H. Wu, Chenxu Qu, Caroline E. McNeil, Gerhard Coetzee, Caroline Hayward, Ian J. Deary, Sarah E. Harris, Evropi Theodoratou, Stuart Reid, Marion Walker, Li Yin Ooi, Ken S. Lau, Hongyu Zhao, Li Hsu, Qiuyin Cai, Malcolm G. Dunlop, Stephen B. Gruber, Richard S. Houlston, Victor Moreno, Graham Casey, Ulrike Peters, Ian Tomlinson, and Wei Zheng
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Science - Abstract
Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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- 2024
- Full Text
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16. Comparative differences in musculoskeletal pain consultation and analgesic prescription for people with dementia
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Bullock, L, Bedson, J, Chen, Y, Chew-Graham, CA, and Campbell, P
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RC925 ,RA0421 ,mental disorders ,RA ,RC - Abstract
Painful musculoskeletal conditions are common in older adults, however pain identification, assessment, and management are reported to be suboptimal for people with dementia. Adequate pain management is an integral aspect of care for people with dementia to prevent or delay negative outcomes, such as behavioural and psychological changes, emergency department attendance, and premature nursing home admission. This study aims to examine musculoskeletal consultations and analgesic prescriptions for people with dementia compared to people without dementia. A dementia cohort (n=36,582) and matched cohort were identified in the Clinical Practice Research Datalink (a UK wide primary care database). Period prevalence for musculoskeletal consultations and analgesic prescriptions were described and logistic regression applied to estimate associations between dementia and musculoskeletal consultation/analgesic prescription from time of dementia diagnosis to 5 years post diagnosis. People with dementia had a consistently (over time) lower prevalence and odds of musculoskeletal consultation and analgesic prescription compared to people without dementia. The evidence suggests that pain management may be suboptimal for people with dementia. These results highlight the need to understand more about practical methods to increase awareness of pain and to employ better methods of pain assessment, evaluation of treatment response and acceptable and effective management for people with dementia, in primary care.
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- 2021
17. Challenges of COVID-19 Case Forecasting in the US, 2020-2021.
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Velma K Lopez, Estee Y Cramer, Robert Pagano, John M Drake, Eamon B O'Dea, Madeline Adee, Turgay Ayer, Jagpreet Chhatwal, Ozden O Dalgic, Mary A Ladd, Benjamin P Linas, Peter P Mueller, Jade Xiao, Johannes Bracher, Alvaro J Castro Rivadeneira, Aaron Gerding, Tilmann Gneiting, Yuxin Huang, Dasuni Jayawardena, Abdul H Kanji, Khoa Le, Anja Mühlemann, Jarad Niemi, Evan L Ray, Ariane Stark, Yijin Wang, Nutcha Wattanachit, Martha W Zorn, Sen Pei, Jeffrey Shaman, Teresa K Yamana, Samuel R Tarasewicz, Daniel J Wilson, Sid Baccam, Heidi Gurung, Steve Stage, Brad Suchoski, Lei Gao, Zhiling Gu, Myungjin Kim, Xinyi Li, Guannan Wang, Lily Wang, Yueying Wang, Shan Yu, Lauren Gardner, Sonia Jindal, Maximilian Marshall, Kristen Nixon, Juan Dent, Alison L Hill, Joshua Kaminsky, Elizabeth C Lee, Joseph C Lemaitre, Justin Lessler, Claire P Smith, Shaun Truelove, Matt Kinsey, Luke C Mullany, Kaitlin Rainwater-Lovett, Lauren Shin, Katharine Tallaksen, Shelby Wilson, Dean Karlen, Lauren Castro, Geoffrey Fairchild, Isaac Michaud, Dave Osthus, Jiang Bian, Wei Cao, Zhifeng Gao, Juan Lavista Ferres, Chaozhuo Li, Tie-Yan Liu, Xing Xie, Shun Zhang, Shun Zheng, Matteo Chinazzi, Jessica T Davis, Kunpeng Mu, Ana Pastore Y Piontti, Alessandro Vespignani, Xinyue Xiong, Robert Walraven, Jinghui Chen, Quanquan Gu, Lingxiao Wang, Pan Xu, Weitong Zhang, Difan Zou, Graham Casey Gibson, Daniel Sheldon, Ajitesh Srivastava, Aniruddha Adiga, Benjamin Hurt, Gursharn Kaur, Bryan Lewis, Madhav Marathe, Akhil Sai Peddireddy, Przemyslaw Porebski, Srinivasan Venkatramanan, Lijing Wang, Pragati V Prasad, Jo W Walker, Alexander E Webber, Rachel B Slayton, Matthew Biggerstaff, Nicholas G Reich, and Michael A Johansson
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Biology (General) ,QH301-705.5 - Abstract
During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.
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- 2024
- Full Text
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18. Interventions for preventing relapse or recurrence of major depressive disorder in adults in a primary care setting: a network meta-analysis
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Moriarty, AS, Robertson, L, Mughal, F, Cook, N, Gilbody, S, McMillan, D, Chew-Graham, CA, Ali, S, Hetrick, SE, Churchill, R, Meader, N, Moriarty, AS, Robertson, L, Mughal, F, Cook, N, Gilbody, S, McMillan, D, Chew-Graham, CA, Ali, S, Hetrick, SE, Churchill, R, and Meader, N
- Published
- 2021
19. The Headache in Emergency Departments study: Opioid prescribing in patients presenting with headache. A multicenter, cross-sectional, observational study
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Pellatt, RAF, Kamona, S, Chu, K, Sweeny, A, Sen Kuan, W, Kinnear, FB, Karamercan, MA, Klim, S, Wijeratne, T, Graham, CA, Body, R, Roberts, T, Horner, D, Laribi, S, Keijzers, G, Kelly, A-M, Pellatt, RAF, Kamona, S, Chu, K, Sweeny, A, Sen Kuan, W, Kinnear, FB, Karamercan, MA, Klim, S, Wijeratne, T, Graham, CA, Body, R, Roberts, T, Horner, D, Laribi, S, Keijzers, G, and Kelly, A-M
- Abstract
OBJECTIVE: To describe the patterns of opioid use in patients presenting to the emergency department (ED) with nontraumatic headache by severity and geography. BACKGROUND: International guidelines recognize opioids are ineffective in treating primary headache disorders. Globally, many countries are experiencing an opioid crisis. The ED can be a point of initial exposure leading to tolerance for patients. More geographically diverse data are required to inform practice. METHODS: This was a planned, multicenter, cross-sectional, observational substudy of the international Headache in Emergency Departments (HEAD) study. Participants were prospectively identified throughout March 2019 from 67 hospitals in Europe, Asia, Australia, and New Zealand. Adult patients with nontraumatic headache were included as identified by the local site investigator. RESULTS: Overall, 4536 patients were enrolled in the HEAD study. Opioids were administered in 1072/4536 (23.6%) patients in the ED, and 386/3792 (10.2%) of discharged patients. High opioid use occurred prehospital in Australia (190/1777, 10.7%) and New Zealand (55/593, 9.3%). Opioid use in the ED was highest in these countries (Australia: 586/1777, 33.0%; New Zealand: 221/593, 37.3%). Opioid prescription on discharge was highest in Singapore (125/442, 28.3%) and Hong Kong (12/49, 24.5%). Independent predictors of ED opioid administration included the following: severe headache (OR 4.2, 95% CI 3.1-5.5), pre-ED opioid use (OR 1.42, 95% CI 1.11-1.82), and long-term opioid use (OR 1.80, 95% CI 1.26-2.58). ED opioid administration independently predicted opioid prescription at discharge (OR 8.4, 95% CI 6.3-11.0). CONCLUSION: Opioid prescription for nontraumatic headache in the ED and on discharge varies internationally. Severe headache, prehospital opioid use, and long-term opioid use predicted ED opioid administration. ED opioid administration was a strong predictor of opioid prescription at discharge. These findings support educat
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- 2021
20. Clinical presentation and assessment of older patients presenting with headache to emergency departments: A multicentre observational study
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Beck, S, Kinnear, FB, Maree Kelly, A, Chu, KH, Sen Kuan, W, Keijzers, G, Body, R, Karamercan, MA, Klim, S, Wijeratne, T, Kamona, S, Graham, CA, Roberts, T, Horner, D, Laribi, S, Beck, S, Kinnear, FB, Maree Kelly, A, Chu, KH, Sen Kuan, W, Keijzers, G, Body, R, Karamercan, MA, Klim, S, Wijeratne, T, Kamona, S, Graham, CA, Roberts, T, Horner, D, and Laribi, S
- Abstract
OBJECTIVE: To describe the characteristics, assessment and management of older emergency department (ED) patients with non-traumatic headache. METHODS: Planned sub-study of a prospective, multicentre, international, observational study, which included adult patients presenting to ED with non-traumatic headache. Patients aged ≥75 years were compared to those aged <75 years. Outcomes of interest were epidemiology, investigations, serious headache diagnosis and outcome. RESULTS: A total of 298 patients (7%) in the parent study were aged ≥75 years. Older patients were less likely to report severe headache pain or subjective fever (both P < 0.001). On examination, older patients were more likely to be confused, have lower Glasgow Coma Scores and to have new neurological deficits (all P < 0.001). Serious secondary headache disorder (composite of headache due to subarachnoid haemorrhage (SAH), intracranial haemorrhage, meningitis, encephalitis, cerebral abscess, neoplasm, hydrocephalus, vascular dissection, stroke, hypertensive crisis, temporal arteritis, idiopathic intracranial hypertension or ventriculoperitoneal shunt complications) was diagnosed in 18% of older patients compared to 6% of younger patients (P < 0.001). Computed tomography brain imaging was performed in 66% of patients ≥75 years compared to 35% of younger patients (P < 0.001). Older patients were less likely to be discharged (43% vs 63%, P < 0.001). CONCLUSIONS: Older patients with headache had different clinical features to the younger cohort and were more likely to have a serious secondary cause of headache than younger adults. There should be a low threshold for investigation in older patients attending ED with non-traumatic headache.
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- 2021
21. Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial
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Chan, EW, Lao, KSJ, Lam, L, Tsui, S-H, Lui, C-T, Wong, C-P, Graham, CA, Cheng, C-H, Chung, T-S, Lam, H-F, Ting, S-M, Knott, JC, Taylor, DM, Kong, DCM, Leung, L-P, Wong, ICK, Chan, EW, Lao, KSJ, Lam, L, Tsui, S-H, Lui, C-T, Wong, C-P, Graham, CA, Cheng, C-H, Chung, T-S, Lam, H-F, Ting, S-M, Knott, JC, Taylor, DM, Kong, DCM, Leung, L-P, and Wong, ICK
- Abstract
BACKGROUND: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. METHODS: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). FINDINGS: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. INTERPRETATION: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. FUNDING: Research Grants Council, Hong Kong.
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- 2021
22. Epidemiology, investigation, management, and outcome of headache in emergency departments (HEAD study)-A multinational observational study
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Kelly, AM, Kuan, WS, Chu, KH, Kinnear, FB, Keijzers, G, Karamercan, MA, Klim, S, Wijeratne, T, Kamona, S, Graham, CA, Body, R, Roberts, T, Horner, D, Laribi, S, Kelly, AM, Kuan, WS, Chu, KH, Kinnear, FB, Keijzers, G, Karamercan, MA, Klim, S, Wijeratne, T, Kamona, S, Graham, CA, Body, R, Roberts, T, Horner, D, and Laribi, S
- Abstract
OBJECTIVE: To describe the epidemiology of nontraumatic headache in adults presenting to emergency departments (EDs). BACKGROUND: Headache is a common reason for presentation to EDs. Little is known about the epidemiology, investigation, and treatment of nontraumatic headache in patients attending EDs internationally. METHODS: An international, multicenter, observational, cross-sectional study was conducted over one calendar month in 2019. Participants were adults (≥18 years) with nontraumatic headache as the main presenting complaint. Exclusion criteria were recent head trauma, missing records, interhospital transfers, re-presentation with same headache as a recent visit, and headache as an associated symptom. Data collected included demographics, clinical assessment, investigation, treatment, and outcome. RESULTS: We enrolled 4536 patients (67 hospitals, 10 countries). "Thunderclap" onset was noted in 14.2% of cases (644/4536). Headache was rated as severe in 27.2% (1235/4536). New neurological examination findings were uncommon (3.2%; 147/4536). Head computed tomography (CT) was performed in 36.6% of patients (1661/4536), of which 9.9% showed clinically important pathology (165/1661). There was substantial variation in CT scan utilization between countries (15.9%-75.0%). More than 30 different diagnoses were made. Presumed nonmigraine benign headache accounted for 45.4% of cases (2058/4536) with another 24.3% classified as migraine (1101/4536). A small subgroup of patients have a serious secondary cause for their headache (7.1%; 323/4536) with subarachnoid hemorrhage (SAH), stroke, neoplasm, non-SAH intracranial hemorrhage/hematoma, and meningitis accounting for about 1% each. Most patients were treated with simple analgesics (paracetamol, aspirin, or nonsteroidal anti-inflammatory agents). Most patients were discharged home (83.8%; 3792/4526). In-hospital mortality was 0.3% (11/4526). CONCLUSION: Diagnosis and management of headache in the ED is challenging. A s
- Published
- 2021
23. Diet Impacts on Gene Expression in Healthy Colon Tissue: Insights from the BarcUVa-Seq Study
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Mireia Obón-Santacana, Ferran Moratalla-Navarro, Elisabet Guinó, Robert Carreras-Torres, Virginia Díez-Obrero, David Bars-Cortina, Gemma Ibáñez-Sanz, Lorena Rodríguez-Alonso, Alfredo Mata, Ana García-Rodríguez, Matthew Devall, Graham Casey, Li Li, and Victor Moreno
- Subjects
diet ,dietary patterns ,gene expression ,tissue ,colon ,nutrigenomics ,Nutrition. Foods and food supply ,TX341-641 - Abstract
(1) Introduction: The global rise of gastrointestinal diseases, including colorectal cancer and inflammatory bowel diseases, highlights the need to understand their causes. Diet is a common risk factor and a crucial regulator of gene expression, with alterations observed in both conditions. This study aims to elucidate the specific biological mechanisms through which diet influences the risk of bowel diseases. (2) Methods: We analyzed data from 436 participants from the BarcUVa-Seq population-based cross-sectional study utilizing gene expression profiles (RNA-Seq) from frozen colonic mucosal biopsies and dietary information from a semi-quantitative food frequency questionnaire. Dietary variables were evaluated based on two dietary patterns and as individual variables. Differential expression gene (DEG) analysis was performed for each dietary factor using edgeR. Protein–protein interaction (PPI) analysis was conducted with STRINGdb v11 for food groups with more than 10 statistically significant DEGs, followed by Reactome-based enrichment analysis for the resulting networks. (3) Results: Our findings reveal that food intake, specifically the consumption of blue fish, alcohol, and potatoes, significantly influences gene expression in the colon of individuals without tumor pathology, particularly in pathways related to DNA repair, immune system function, and protein glycosylation. (4) Discussion: These results demonstrate how these dietary components may influence human metabolic processes and affect the risk of bowel diseases.
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- 2024
- Full Text
- View/download PDF
24. Get with the guidelines: management of chronic obstructive pulmonary disease in emergency departments in Europe and Australasia is sub-optimal
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Kelly, AM, Van Meer, O, Keijzers, G, Motiejunaite, J, Jones, P, Body, R, Craig, S, Karamercan, M, Klim, S, Harjola, VP, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Graham, CA, Capsec, J, Barletta, C, Garcia-Castrillo, L, Kuan, WS, Laribi, S, McNulty, R, Tan, C, Cowell, DL, Jain, N, Devillecourt, T, Forrester, A, Lee, K, Chalkley, D, Gillett, M, Lozzi, L, Asha, S, Duffy, M, Watkins, G, Stone, R, Rosengren, D, Thone, J, Martin, S, Orda, U, Thom, O, Kinnear, F, Eley, R, Ryan, A, Morel, D, May, C, Furyk, Jeremy, Thomson, G, Smith, S, Smith, R, Maclean, A, Grummisch, M, Meyer, A, Meek, R, Rosengarten, P, Chan, B, Haythorne, H, Archer, P, Wilson, K, Knott, J, Ritchie, P, Bryant, M, MacDonald, S, Lee, T, Mahlangu, M, Mountain, D, Rogers, I, Otto, T, Stuart, P, Bament, J, Brown, M, Greven-Garcia, R, Scott, M, Cheri, T, Nguyen, M, Wong, CP, Wong, TW, Leung, LP, Man, CK, Saiboon, IM, Rahman, NH, Lee, WY, Lee, FCY, Russell, SK, Lawoko, C, Al Dandachi, G, Maignan, M, Hermand, DC, Tessier, C, Roy, PM, Bucco, L, Duytsche, N, Garmilla, P, Carbone, G, Cosentini, R, Truță, S, Hrihorișan, N, Cimpoeșu, D, Rotaru, L, Petrică, A, Cojocaru, M, Kelly, AM, Van Meer, O, Keijzers, G, Motiejunaite, J, Jones, P, Body, R, Craig, S, Karamercan, M, Klim, S, Harjola, VP, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Graham, CA, Capsec, J, Barletta, C, Garcia-Castrillo, L, Kuan, WS, Laribi, S, McNulty, R, Tan, C, Cowell, DL, Jain, N, Devillecourt, T, Forrester, A, Lee, K, Chalkley, D, Gillett, M, Lozzi, L, Asha, S, Duffy, M, Watkins, G, Stone, R, Rosengren, D, Thone, J, Martin, S, Orda, U, Thom, O, Kinnear, F, Eley, R, Ryan, A, Morel, D, May, C, Furyk, Jeremy, Thomson, G, Smith, S, Smith, R, Maclean, A, Grummisch, M, Meyer, A, Meek, R, Rosengarten, P, Chan, B, Haythorne, H, Archer, P, Wilson, K, Knott, J, Ritchie, P, Bryant, M, MacDonald, S, Lee, T, Mahlangu, M, Mountain, D, Rogers, I, Otto, T, Stuart, P, Bament, J, Brown, M, Greven-Garcia, R, Scott, M, Cheri, T, Nguyen, M, Wong, CP, Wong, TW, Leung, LP, Man, CK, Saiboon, IM, Rahman, NH, Lee, WY, Lee, FCY, Russell, SK, Lawoko, C, Al Dandachi, G, Maignan, M, Hermand, DC, Tessier, C, Roy, PM, Bucco, L, Duytsche, N, Garmilla, P, Carbone, G, Cosentini, R, Truță, S, Hrihorișan, N, Cimpoeșu, D, Rotaru, L, Petrică, A, and Cojocaru, M
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- 2020
25. Get with the guidelines: management of chronic obstructive pulmonary disease in emergency departments in Europe and Australasia is sub-optimal
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Kelly, A-M, Van Meer, O, Keijzers, G, Motiejunaite, J, Jones, P, Body, R, Craig, S, Karamercan, M, Klim, S, Harjola, V-P, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Graham, CA, Capsec, J, Barletta, C, Garcia-Castrillo, L, Kuan, WS, Laribi, S, Kelly, A-M, Van Meer, O, Keijzers, G, Motiejunaite, J, Jones, P, Body, R, Craig, S, Karamercan, M, Klim, S, Harjola, V-P, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Graham, CA, Capsec, J, Barletta, C, Garcia-Castrillo, L, Kuan, WS, and Laribi, S
- Abstract
Background Exacerbations of chronic obstructive pulmonary disease (COPD) are common in emergency departments (ED). Guidelines recommend administration of inhaled bronchodilators, systemic corticosteroids and antibiotics along with non-invasive ventilation (NIV) for patients with respiratory acidosis. Aim To determine compliance with guideline recommendations for patients treated for COPD in ED in Europe (EUR) and South East Asia/Australasia (SEA) and to compare management and outcomes. Methods In each region, an observational prospective cohort study was performed that included patients presenting to ED with the main complaint of dyspnoea during three 72-h periods. This planned sub-study included those with an ED primary discharge diagnosis of COPD. Data were collected on demographics, clinical features, treatment, disposition and in-hospital mortality. We determined overall compliance with guideline recommendations and compared treatments and outcome between regions. Results A total of 801 patients was included from 122 ED (66 EUR and 46 SEA). Inhaled bronchodilators were administered to 80.3% of patients, systemic corticosteroids to 59.5%, antibiotics to 44 and 60.6% of patients with pH <7.3 received NIV. The proportion administered systemic corticosteroids was higher in SEA (EUR vs SEA for all comparisons; 52 vs 66%, P < 0.001) as was administration of antibiotics (40 vs 49%, P = 0.02). Rates of NIV and mechanical ventilation were similar. Overall in-hospital mortality was 4.2% (SEA 3.9% vs EUR 4.5%, P = 0.77). Conclusion Compliance with guideline recommended treatments, in particular administration of corticosteroids and NIV, was sub-optimal in both regions. Improved compliance has the potential to improve patient outcome.
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- 2020
26. Chronic disease management in emergency department patients presenting with dyspnoea
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Jones, P, Kelly, A-M, Keijzers, G, Klim, S, Holdgate, A, Graham, CA, Craig, S, Kuan, WS, Laribi, S, Jones, P, Kelly, A-M, Keijzers, G, Klim, S, Holdgate, A, Graham, CA, Craig, S, Kuan, WS, and Laribi, S
- Abstract
OBJECTIVES: Guideline recommended treatments for chronic conditions are thought to reduce ED presentations. METHOD: We used data from 1958 ED patients with dyspnoea to describe medication use in patients with chronic conditions. RESULTS: A total of 1233 (63.5%) patients had one or more of: chronic obstructive pulmonary disease 547 (28%), asthma 454 (23%), atrial fibrillation 368 (19%) or heart failure 401 (21%). Approximately, 70% were prescribed appropriate preventative medication for their chronic condition when they presented to ED with dyspnoea. CONCLUSION: Prescription of guideline recommended therapies for chronic conditions in patients presenting to the ED in Australasia with acute dyspnoea is similar or higher than reported previously.
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- 2020
27. Early lessons from COVID-19 that may reduce future emergency department crowding.
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Mazurik, L, Javidan, AP, Higginson, I, Judkins, S, Petrie, D, Graham, CA, Bonning, J, Hansen, K, Lang, E, Mazurik, L, Javidan, AP, Higginson, I, Judkins, S, Petrie, D, Graham, CA, Bonning, J, Hansen, K, and Lang, E
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The COVID-19 pandemic has produced significant changes in emergency medicine patient volumes, clinical practice, and has accelerated a number of systems-level developments. Many of these changes produced efficiencies in emergency care systems and contributed to a reduction in crowding and access block. In this paper, we explore these changes, analyse their risks and benefits and examine their sustainability for the future to the extent that they may combat crowding. We also examine the necessity of a system-wide approach in addressing ED crowding and access block.
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- 2020
28. Study design: A research primer for low- and middle-income countries
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Graham, CA, Simon, EL, Knott, J, Graham, CA, Simon, EL, and Knott, J
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Study design is critical to ensure that research questions are answered in an appropriate and rational manner for all aspects of health, but particularly in emergency care. Appropriate study design selection is one of the most critical decisions to make at the earliest stage of a research project; once this is clear, much of the methodology and sample size estimations should be straightforward. Selection of an appropriate study design is fundamental to good research and deserves careful consideration at the outset of any research project. The classic gold standard for study design is the double-blind randomised clinical trial, but it is often not possible to achieve this ideal in the busy clinical emergency environment or with the resources available. Descriptive studies are common in emergency care; they include retrospective clinical records reviews, prospective cohort studies and case-control studies. Case reports and surveys can be a useful introduction to research for novice researchers. When sufficient empirical evidence on a topic exists, results of similar studies can be combined in systematic reviews and/or meta-analyses to pool the results from multiple studies to determine stronger evidence for or against an intervention or treatment, but these techniques require specialist expertise and statistical skills.
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- 2020
29. Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study
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Luethi, N, Bailey, M, Higgins, A, Howe, B, Peake, S, Delaney, A, Bellomo, R, Bennett, V, Board, J, McCracken, P, McGloughlin, S, Nanjayya, V, Teo, A, Hill, E, O'Brien, PJE, Sawtell, F, Schimanski, K, Wilson, D, Bolch, S, Eastwood, G, Kerr, F, Peak, L, Young, H, Edington, J, Fletcher, J, Smith, J, Ghelani, D, Nand, K, Sara, T, Cross, A, Flemming, D, Grummisch, M, Purdue, A, Fulton, E, Grove, K, Harney, A, Milburn, K, Millar, R, Mitchell, I, Rodgers, H, Scanlon, S, Coles, T, Connor, H, Dennett, J, Van Berkel, A, Barrington-Onslow, S, Henderson, S, Mehrtens, J, Dryburgh, J, Tankel, A, Braitberg, G, O'Bree, B, Shepherd, K, Vij, S, Allsop, S, Haji, D, Haji, K, Vuat, J, Bone, A, Elderkin, T, Orford, N, Ragg, M, Kelly, S, Stewart, D, Woodward, N, Harjola, V-P, Pettila, MO, Sutinen, S, Wilkman, E, Fratzia, J, Halkhoree, J, Treloar, S, Ryan, K, Sandford, T, Walsham, J, Jenkins, C, Williamson, D, Burrows, J, Hawkins, D, Tang, C, Dimakis, A, Holdgate, A, Micallef, S, Parr, M, White, H, Morrison, L, Sosnowski, K, Ramadoss, R, Soar, N, Wood, J, Franks, M, Williams, A, Hogan, C, Song, R, Tilsley, A, Rainsford, D, Wells, R, Dowling, J, Galt, P, Lamac, T, Lightfoot, D, Walker, C, Braid, K, DeVillecourt, T, Tan, HS, Seppelt, I, Chang, LF, Cheung, WS, Fok, SK, Lam, PK, Lam, SM, So, HM, Yan, W, Altea, A, Lancashire, B, Gomersall, CD, Graham, CA, Leung, P, Arora, S, Bass, F, Shehabi, Y, Isoardi, J, Isoardi, K, Powrie, D, Lawrence, S, Ankor, A, Chester, L, Davies, M, O'Connor, S, Poole, A, Soulsby, T, Sundararajan, K, Williams, J, Greenslade, JH, MacIsaac, C, Gorman, K, Jordan, A, Moore, L, Ankers, S, Bird, S, Fogg, T, Hickson, E, Jewell, T, Kyneur, K, O'Connor, A, Townsend, J, Yarad, E, Brown, S, Chamberlain, J, Cooper, J, Jenkinson, E, McDonald, E, Webb, S, Buhr, H, Coakley, J, Cowell, J, Hutch, D, Gattas, D, Keir, M, Rajbhandari, D, Rees, C, Baker, S, Roberts, B, Farone, E, Holmes, J, Santamaria, J, Winter, C, Finckh, A, Knowles, S, McCabe, J, Nair, P, Reynolds, C, Ahmed, B, Barton, D, Meaney, E, Nichol, A, Harris, R, Shields, L, Thomas, K, Karlsson, S, Kuitunen, A, Kukkurainen, A, Tenhunen, J, Varila, S, Ryan, N, Trethewy, C, Crosdale, J, Smith, JC, Vellaichamy, M, Furyk, J, Gordon, G, Jones, L, Senthuran, S, Bates, S, Butler, J, French, C, Tippett, A, Kelly, J, Kwans, J, Murphy, M, O'Flynn, D, Kurenda, C, Otto, T, Raniga, V, Williams, P, Ho, HF, Leung, A, Wu, H, Luethi, N, Bailey, M, Higgins, A, Howe, B, Peake, S, Delaney, A, Bellomo, R, Bennett, V, Board, J, McCracken, P, McGloughlin, S, Nanjayya, V, Teo, A, Hill, E, O'Brien, PJE, Sawtell, F, Schimanski, K, Wilson, D, Bolch, S, Eastwood, G, Kerr, F, Peak, L, Young, H, Edington, J, Fletcher, J, Smith, J, Ghelani, D, Nand, K, Sara, T, Cross, A, Flemming, D, Grummisch, M, Purdue, A, Fulton, E, Grove, K, Harney, A, Milburn, K, Millar, R, Mitchell, I, Rodgers, H, Scanlon, S, Coles, T, Connor, H, Dennett, J, Van Berkel, A, Barrington-Onslow, S, Henderson, S, Mehrtens, J, Dryburgh, J, Tankel, A, Braitberg, G, O'Bree, B, Shepherd, K, Vij, S, Allsop, S, Haji, D, Haji, K, Vuat, J, Bone, A, Elderkin, T, Orford, N, Ragg, M, Kelly, S, Stewart, D, Woodward, N, Harjola, V-P, Pettila, MO, Sutinen, S, Wilkman, E, Fratzia, J, Halkhoree, J, Treloar, S, Ryan, K, Sandford, T, Walsham, J, Jenkins, C, Williamson, D, Burrows, J, Hawkins, D, Tang, C, Dimakis, A, Holdgate, A, Micallef, S, Parr, M, White, H, Morrison, L, Sosnowski, K, Ramadoss, R, Soar, N, Wood, J, Franks, M, Williams, A, Hogan, C, Song, R, Tilsley, A, Rainsford, D, Wells, R, Dowling, J, Galt, P, Lamac, T, Lightfoot, D, Walker, C, Braid, K, DeVillecourt, T, Tan, HS, Seppelt, I, Chang, LF, Cheung, WS, Fok, SK, Lam, PK, Lam, SM, So, HM, Yan, W, Altea, A, Lancashire, B, Gomersall, CD, Graham, CA, Leung, P, Arora, S, Bass, F, Shehabi, Y, Isoardi, J, Isoardi, K, Powrie, D, Lawrence, S, Ankor, A, Chester, L, Davies, M, O'Connor, S, Poole, A, Soulsby, T, Sundararajan, K, Williams, J, Greenslade, JH, MacIsaac, C, Gorman, K, Jordan, A, Moore, L, Ankers, S, Bird, S, Fogg, T, Hickson, E, Jewell, T, Kyneur, K, O'Connor, A, Townsend, J, Yarad, E, Brown, S, Chamberlain, J, Cooper, J, Jenkinson, E, McDonald, E, Webb, S, Buhr, H, Coakley, J, Cowell, J, Hutch, D, Gattas, D, Keir, M, Rajbhandari, D, Rees, C, Baker, S, Roberts, B, Farone, E, Holmes, J, Santamaria, J, Winter, C, Finckh, A, Knowles, S, McCabe, J, Nair, P, Reynolds, C, Ahmed, B, Barton, D, Meaney, E, Nichol, A, Harris, R, Shields, L, Thomas, K, Karlsson, S, Kuitunen, A, Kukkurainen, A, Tenhunen, J, Varila, S, Ryan, N, Trethewy, C, Crosdale, J, Smith, JC, Vellaichamy, M, Furyk, J, Gordon, G, Jones, L, Senthuran, S, Bates, S, Butler, J, French, C, Tippett, A, Kelly, J, Kwans, J, Murphy, M, O'Flynn, D, Kurenda, C, Otto, T, Raniga, V, Williams, P, Ho, HF, Leung, A, and Wu, H
- Abstract
PURPOSE: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. MATERIAL AND METHODS: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years). RESULTS: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46-1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. CONCLUSIONS: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group.
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- 2020
30. Epidemiology, treatment and outcome of patients with lower respiratory tract infection presenting to emergency departments with dyspnoea (AANZDEMandEuroDEMstudies)
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Rousseau, G, Keijzers, G, van Meer, O, Craig, S, Karamercan, M, Klim, S, Body, R, Kuan, WS, Harjola, V-P, Jones, P, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Capsec, J, Barletta, C, Graham, CA, Garcia-Castrillo, L, Laribi, S, Kelly, A-M, Rousseau, G, Keijzers, G, van Meer, O, Craig, S, Karamercan, M, Klim, S, Body, R, Kuan, WS, Harjola, V-P, Jones, P, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Capsec, J, Barletta, C, Graham, CA, Garcia-Castrillo, L, Laribi, S, and Kelly, A-M
- Abstract
OBJECTIVE: Lower respiratory tract infection (LRTI) is a frequent cause of dyspnoea in EDs, and is associated with considerable morbidity and mortality. We described and compared the management of this disease in Europe and Oceania/South-East Asia (SEA) cohorts. METHODS: We conducted a prospective cohort study with three time points in Europe and Oceania/SEA. We included in this manuscript patients presenting to EDs with dyspnoea and a diagnosis of LRTI in ED. We collected comorbidities, chronic medication, clinical signs at arrival, laboratory parameters, ED management and patient outcomes. RESULTS: A total of 1389 patients were included, 773 in Europe and 616 in SEA. The European cohort had more comorbidities including chronic heart failure, obesity, chronic obstructive pulmonary disease and smoking. Levels of inflammatory markers were higher in Europe. There were more patients with inflammatory markers in Europe and more hypercapnia in Oceania/SEA. The use of antibiotics was higher in SEA (72.2% vs 61.8%, P < 0.001) whereas intravenous diuretics, non-invasive and invasive ventilation were higher in Europe. Intensive care unit admission rate was 9.9% in Europe cohort and 3.4% in Oceania/SEA cohort. ED mortality was 1% and overall in-hospital mortality was 8.7% with no differences between regions. CONCLUSIONS: More patients with LRTI in Europe presented with cardio-respiratory comorbidities, they received more adjunct therapies and had a higher intensive care unit admission rate than patients from Oceania/SEA, although mortality was similar between the two cohorts.
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- 2020
31. Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
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Minta Thomas, Yu-Ru Su, Elisabeth A. Rosenthal, Lori C. Sakoda, Stephanie L. Schmit, Maria N. Timofeeva, Zhishan Chen, Ceres Fernandez-Rozadilla, Philip J. Law, Neil Murphy, Robert Carreras-Torres, Virginia Diez-Obrero, Franzel J. B. van Duijnhoven, Shangqing Jiang, Aesun Shin, Alicja Wolk, Amanda I. Phipps, Andrea Burnett-Hartman, Andrea Gsur, Andrew T. Chan, Ann G. Zauber, Anna H. Wu, Annika Lindblom, Caroline Y. Um, Catherine M. Tangen, Chris Gignoux, Christina Newton, Christopher A. Haiman, Conghui Qu, D. Timothy Bishop, Daniel D. Buchanan, David R. Crosslin, David V. Conti, Dong-Hyun Kim, Elizabeth Hauser, Emily White, Erin Siegel, Fredrick R. Schumacher, Gad Rennert, Graham G. Giles, Heather Hampel, Hermann Brenner, Isao Oze, Jae Hwan Oh, Jeffrey K. Lee, Jennifer L. Schneider, Jenny Chang-Claude, Jeongseon Kim, Jeroen R. Huyghe, Jiayin Zheng, Jochen Hampe, Joel Greenson, John L. Hopper, Julie R. Palmer, Kala Visvanathan, Keitaro Matsuo, Koichi Matsuda, Keum Ji Jung, Li Li, Loic Le Marchand, Ludmila Vodickova, Luis Bujanda, Marc J. Gunter, Marco Matejcic, Mark A. Jenkins, Martha L. Slattery, Mauro D’Amato, Meilin Wang, Michael Hoffmeister, Michael O. Woods, Michelle Kim, Mingyang Song, Motoki Iwasaki, Mulong Du, Natalia Udaltsova, Norie Sawada, Pavel Vodicka, Peter T. Campbell, Polly A. Newcomb, Qiuyin Cai, Rachel Pearlman, Rish K. Pai, Robert E. Schoen, Robert S. Steinfelder, Robert W. Haile, Rosita Vandenputtelaar, Ross L. Prentice, Sébastien Küry, Sergi Castellví-Bel, Shoichiro Tsugane, Sonja I. Berndt, Soo Chin Lee, Stefanie Brezina, Stephanie J. Weinstein, Stephen J. Chanock, Sun Ha Jee, Sun-Seog Kweon, Susan Vadaparampil, Tabitha A. Harrison, Taiki Yamaji, Temitope O. Keku, Veronika Vymetalkova, Volker Arndt, Wei-Hua Jia, Xiao-Ou Shu, Yi Lin, Yoon-Ok Ahn, Zsofia K. Stadler, Bethany Van Guelpen, Cornelia M. Ulrich, Elizabeth A. Platz, John D. Potter, Christopher I. Li, Reinier Meester, Victor Moreno, Jane C. Figueiredo, Graham Casey, Iris Lansdorp Vogelaar, Malcolm G. Dunlop, Stephen B. Gruber, Richard B. Hayes, Paul D. P. Pharoah, Richard S. Houlston, Gail P. Jarvik, Ian P. Tomlinson, Wei Zheng, Douglas A. Corley, Ulrike Peters, and Li Hsu
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Science - Abstract
Abstract Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values
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- 2023
- Full Text
- View/download PDF
32. The role of primary care supporting older adults who self-harm: a qualitative study
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Troya, MI, Chew-Graham, CA, Babatunde, OO, Bartlam, B, Mughal, F, and Dikomitis, L
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R1 - Abstract
Background\ud Self-harm and suicide are major public health concerns. Self-harm is the strongest risk factor for suicide, with amongst the highest suicide rates reported in older populations. Little is known about how older adults access care following self-harm, but they are in frequent contact with primary care.\ud \ud Aim\ud Identify and explore barriers and facilitators for accessing care within primary care for older adults who self-harm. Design and Setting An exploratory qualitative methods study using semi-structured interviews with older adults and third sector workers in England. Older adults invited to participate in one follow-up interview.\ud \ud Method\ud Interviews occurred between September 2017 and September 2018. These were audio-recorded, transcribed verbatim and data analysed thematically. A Patient Public Involvement Engagement group contributed to study design, data analysis and interpretation. Keele University granted ethical approval. Results Twenty-four interviews with nine older adults and seven support workers, including eight follow-up interviews with older adults. Three themes emerged: i) help-seeking decision factors; ii) sources of support; iii) barriers and facilitators to accessing primary care.\ud \ud Conclusion\ud Despite older adults’ frequent contact with general practitioners, barriers to primary care existed which included stigma, previous negative experiences and practical barriers such as mobility restrictions. Older adults’ help-seeking behaviour was facilitated by previous positive experiences. Primary care is a potential avenue for delivering effective self-harm support, management and suicide prevention in older adults. Given the complex nature of self-harm, there is a need for primary care to work with other sectors to provide comprehensive support to older adults who self-harm.
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- 2019
33. Depression predicts emergency care use in people with Chronic Obstructive Pulmonary Disease: A large cohort study in primary care
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Blakemore, A, Dickens, C, Chew-Graham, CA, Afzal, CW, Tomenson, B, Coventry, PA, and Guthrie, E
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RC705 ,International Journal of Chronic Obstructive Pulmonary Disease ,R1 ,RA - Abstract
A Blakemore,1 C Dickens,2 CA Chew-Graham,3 CW Afzal,4 B Tomenson,5 PA Coventry,6 E Guthrie71Division of Nursing, Social Work and Midwifery, School of Health Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 2University of Exeter Medical School, Exeter, St Luke’s Campus, Exeter, UK; 3Research Institute, Primary Care and Health Sciences, West Midlands CLAHRC, Keele, University, Newcastle, UK; 4Health Innovation Manchester, Greater Manchester’s Academic Health Science Network, Manchester Academic Health Science Centre, Manchester, UK; 5Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK; 6Department of Health Sciences, University of York, York, UK; 7Leeds Institute of Health Sciences, Faculty of Medicine and Health, University of Leeds, Leeds, UKBackground: Depression is common in people with chronic obstructive pulmonary disease (COPD) and has been associated with a variety of poor outcomes. A large proportion of health care costs in the UK are spent on emergency care. This study examined the prospective relationship between depression and use of emergency care in patients with COPD managed in primary care.Methods: This was a twelve-month, prospective longitudinal study of 355 patients with COPD in six primary care practices in the UK. Baseline measures included demographic characteristics, depression and anxiety, severity of COPD, presence or absence of other chronic diseases, and prior use of emergency care. Outcome measures were (a) number of emergency department (ED) visits; or (b) an emergency hospital admission in the follow-up year.Results: Older age, number of comorbid physical health conditions, severity of COPD, prior use of emergency care, and depression were all independently associated with both ED attendance and an emergency hospital admission in the follow-up year. Subthreshold depression (HADS depression score 4–7) was associated with a 2.8 times increased odds of emergency hospital admission, and HADS depression >8 was associated with 4.8 times increased odds.Conclusion: Depression is a predictor of emergency care in COPD, independent of severity of disease or physical comorbidity. Even mild (subthreshold) symptoms of depression more than double the risk of using emergency care, suggesting there is a strong case to develop and deploy integrated preventive strategies in primary care that can promote mental health in people with COPD.Keywords: COPD, depression, anxiety, emergency care, United Kingdom, hospital admission, primary care
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- 2019
34. Cost-utility Analysis of Routine Anxiety and Depression Screening in Patients Consulting for Osteoarthritis: results from the POST Trial
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Kigozi, J, Jowett, S, Nicholl, BI, Lewis, M, Bartlam, B, Green, D, Belcher, J, Clarkson, K, Lingard, Z, Pope, C, Chew-Graham, CA, Croft, P, Hay, EM, Peat, G, and Mallen, CD
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RC925 - Abstract
OBJECTIVE: To investigate the cost-effectiveness (cost-utility) of introducing general practitioner screening for anxiety and depression in patients consulting with osteoarthritis (OA). METHODS: A cluster-randomised trial-based economic evaluation to assess general practitioners screening for anxiety and depression symptoms in patients consulting with OA compared to usual care (screening for pain intensity) was undertaken over a 12-month period from a UK National Health Service and Societal perspective. Patient-level mean costs and mean quality-adjusted life years (QALYs) were estimated and cost-effectiveness acceptability curves controlling for cluster-level data were constructed. The base-case analysis used the net-benefit regressions approach. The two-stage non-parametric sampling technique was explored in a sensitivity analysis. RESULTS: The base-case analysis demonstrated that the intervention was as costly as, and less effective than, the control (QALY diff, 95% CI: - 0.029 (95% CI -0.062 to 0.003)). In the base-case analyses, GP screening for anxiety and depression was unlikely to be a cost-effective option (probability < 5% at £20,000/QALY). Similar results were observed in all sensitivity analyses. CONCLUSIONS: Prompting GP's to routinely screen and manage comorbid anxiety and depression in patients presenting with OA is unlikely to be cost-effective. Further research is needed to explore clinically-effective and cost-effective models of managing anxiety and depression in patients presenting with clinical OA. This article is protected by copyright. All rights reserved.
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- 2018
35. Depression predicts emergency care use in people with chronic obstructive pulmonary disease: a large cohort study in primary care
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Blakemore A, Dickens C, Chew-Graham CA, Afzal CW, Tomenson B, Coventry PA, and Guthrie E
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Male ,Time Factors ,emergency care ,Comorbidity ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,primary care ,Patient Admission ,Risk Factors ,Humans ,COPD ,Longitudinal Studies ,Prospective Studies ,Aged ,Original Research ,lcsh:RC705-779 ,Aged, 80 and over ,Primary Health Care ,Depression ,lcsh:Diseases of the respiratory system ,Middle Aged ,anxiety ,United Kingdom ,Affect ,hospital admission ,Mental Health ,Feasibility Studies ,Female ,Emergency Service, Hospital - Abstract
A Blakemore,1 C Dickens,2 CA Chew-Graham,3 CW Afzal,4 B Tomenson,5 PA Coventry,6 E Guthrie71Division of Nursing, Social Work and Midwifery, School of Health Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 2University of Exeter Medical School, Exeter, St Luke’s Campus, Exeter, UK; 3Research Institute, Primary Care and Health Sciences, West Midlands CLAHRC, Keele, University, Newcastle, UK; 4Health Innovation Manchester, Greater Manchester’s Academic Health Science Network, Manchester Academic Health Science Centre, Manchester, UK; 5Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK; 6Department of Health Sciences, University of York, York, UK; 7Leeds Institute of Health Sciences, Faculty of Medicine and Health, University of Leeds, Leeds, UKBackground: Depression is common in people with chronic obstructive pulmonary disease (COPD) and has been associated with a variety of poor outcomes. A large proportion of health care costs in the UK are spent on emergency care. This study examined the prospective relationship between depression and use of emergency care in patients with COPD managed in primary care.Methods: This was a twelve-month, prospective longitudinal study of 355 patients with COPD in six primary care practices in the UK. Baseline measures included demographic characteristics, depression and anxiety, severity of COPD, presence or absence of other chronic diseases, and prior use of emergency care. Outcome measures were (a) number of emergency department (ED) visits; or (b) an emergency hospital admission in the follow-up year.Results: Older age, number of comorbid physical health conditions, severity of COPD, prior use of emergency care, and depression were all independently associated with both ED attendance and an emergency hospital admission in the follow-up year. Subthreshold depression (HADS depression score 4–7) was associated with a 2.8 times increased odds of emergency hospital admission, and HADS depression >8 was associated with 4.8 times increased odds.Conclusion: Depression is a predictor of emergency care in COPD, independent of severity of disease or physical comorbidity. Even mild (subthreshold) symptoms of depression more than double the risk of using emergency care, suggesting there is a strong case to develop and deploy integrated preventive strategies in primary care that can promote mental health in people with COPD.Keywords: COPD, depression, anxiety, emergency care, United Kingdom, hospital admission, primary care
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- 2018
36. Treatment and outcome of adult patients with acute asthma in emergency departments in Australasia, South East Asia and Europe: Are guidelines followed? AANZDEM/EuroDEM study
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Craig, S, Kuan, WS, Kelly, A-M, Van Meer, O, Motiejunaite, J, Keijzers, G, Jones, P, Body, R, Karamercan, MA, Klim, S, Harjola, V-P, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Graham, CA, Capsec, J, Barletta, C, Garcia-Castrillo, L, Laribi, S, Craig, S, Kuan, WS, Kelly, A-M, Van Meer, O, Motiejunaite, J, Keijzers, G, Jones, P, Body, R, Karamercan, MA, Klim, S, Harjola, V-P, Verschuren, F, Holdgate, A, Christ, M, Golea, A, Graham, CA, Capsec, J, Barletta, C, Garcia-Castrillo, L, and Laribi, S
- Abstract
OBJECTIVE: Asthma exacerbations are common presentations to ED. Key guideline recommendations for management include administration of inhaled bronchodilators, systemic corticosteroids and titrated oxygen therapy. Our aim was to compare management and outcomes between patients treated for asthma in Europe (EUR) and South East Asia/Australasia (SEA) and compliance with international guidelines. METHODS: In each region, prospective, interrupted time series studies were performed including adult (age >18 years) patients presenting to ED with the main complaint of dyspnoea during three 72 h periods. This was a planned sub-study that included those with an ED primary diagnosis of asthma. Data was collected on demographics, clinical features, treatment in ED, diagnosis, disposition and in-hospital outcome. The results of interest were differences in treatment and outcome between EUR and SEA cohorts. RESULTS: Five hundred and eighty-four patients were identified from 112 EDs (66 EUR and 46 SEA). The cohorts had similar demographics and co-morbidity patterns, with 89% of the cohort having a previous diagnosis of asthma. There were no significant differences in treatment between EUR and SEA patients - inhaled beta-agonists were administered in 86% of cases, systemic corticosteroids in 66%, oxygen therapy in 44% and antibiotics in 20%. Two thirds of patients were discharged home from the ED. CONCLUSION: The data suggests that compliance with guideline-recommended therapy in both regions, particularly corticosteroid administration, is sub-optimal. It also suggests over-use of antibiotics.
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- 2019
37. Multi‐omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability
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Matthew Devall, Mourad W. Ali, Stephen Eaton, Daniel J. Weisenberger, Matthew J. Reilley, Steven M. Powell, Li Li, and Graham Casey
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colon organoids ,colorectal cancer ,Lynch syndrome ,microsatellite instability ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Introduction Lynch syndrome (LS) is a hereditary condition that increases the risk of colorectal (CRC) and extracolonic cancers that exhibit microsatellite instability (MSI‐H). MSI‐H is driven by defective mismatch repair (dMMR), and approximately 15% of nonhereditary CRCs also exhibit MSI‐H. Here, we aimed to better define mechanisms underlying tumor initiation in LS and MSI‐H cancers through multi‐omic analyses of LS normal colon organoids and MSI‐H tumors. Methods Right (n = 35) and left (n = 23) colon organoids generated from normal colon biopsies at routine colonoscopy of LS and healthy individuals were subjected to Illumina EPIC array. Differentially methylated region (DMR) analysis was performed by DMRcate. RNA‐sequencing (n = 16) and bisulfite‐sequencing (n = 15) were performed on a subset of right colon organoids. CRISPR‐cas9‐mediated editing of MMR genes in colon organoids of healthy individuals was followed by quantitative PCR of MSH4. The relationship between MSH4 expression and tumor mutational burden was further explored in three independent tumor data sets. Results We identified a hypermethylated region of MSH4 in both the right and left colon organoids of LS versus healthy controls, which we validated using bisulfite‐sequencing. DMR analysis in three gastrointestinal and one endometrial data set revealed that this region was also hypermethylated in MSI‐H versus microsatellite stable (MSS) tumors. MSH4 expression was increased in colon organoids of LS versus healthy subjects and in publicly available MSI‐H versus MSS tumors across four RNA‐seq and four microarray data sets. CRISPR‐cas9 editing of MLH1 and MSH2, but not MSH6, in normal colon organoids significantly increased MSH4 expression. MSH4 expression was significantly associated with tumor mutational burden in three publicly available data sets. Conclusions Our findings implicate DNA methylation and gene expression differences of MSH4 as a marker of dMMR and as a potential novel biomarker of LS. Our study of LS colon organoids supports the hypothesis that dMMR exists in the colons of LS subjects prior to CRC.
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- 2023
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38. Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial
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Ellen James, David Erritzoe, Tiffanie Benway, Zelah Joel, Christopher Timmermann, Meghan Good, Claudio Agnorelli, Brandon M. Weiss, Tommaso Barba, Graham Campbell, Michelle Baker Jones, Charlotte Hughes, Helen Topping, Malcolm Boyce, and Carol Routledge
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dimethyltryptamine ,major depressive disorder ,pharmacodynamic ,psychedelic ,safety ,tolerability ,Psychiatry ,RC435-571 - Abstract
BackgroundDue to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD).AimThe aim of Part A of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate) in psychedelic-naïve healthy participants to determine a dose for administration to patients with MDD in the subsequent Phase 2a part of the trial (Part B: not presented in this manuscript).MethodsIn the Phase 1, randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation trial, psychedelic-naïve participants were randomized to placebo (n = 8) or four different escalating doses [9, 12, 17 and 21.5 mg intravenously (IV)] of SPL026 (n = 6 for each dose) together with psychological support from 2 therapy team members. PK and acute (immediately following dosing experience) psychometric measures [including mystical experience questionnaire (MEQ), ego dissolution inventory (EDI), and intensity rating visual analogue scale (IRVAS)] were determined. Additional endpoints were measured as longer-term change from baseline to days 8, 15, 30 and 90. These measures included the Warwick and Edinburgh mental wellbeing scale and Spielberger’s state-trait anxiety inventory.ResultsSPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events. There was some evidence of a correlation between maximum plasma concentration and increased IRVAS, MEQ, and EDI scores. These trends are likely to require confirmation in a larger sample size. Using the analysis of the safety, tolerability, PD, PK results, doses of 21.5 mg SPL026 were the most likely to provide an intense, tolerated experience.ConclusionBased on the data obtained from this part of the trial, a dose of 21.5 mg SPL026 given as a 2-phase IV infusion over 10 min (6 mg/5 min and 15.5 mg/5 min) was selected as the dose to be taken into patients in Part B (to be presented in a future manuscript).Clinical trial registration:www.clinicaltrials.gov, identifier NCT04673383; https://www.clinicaltrialsregister.eu, identifier 2020-000251-13; https://www.isrctn.com/, identifier ISRCTN63465876.
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- 2024
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39. Use of point-of-care ultrasound (POCUS) by emergency physicians for general surgical patients in resuscitation room
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Cheung, KH, Ong, YS, Graham, CA, Rainer, TH, and Cheung, NK
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- 2014
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40. Focused echocardiogram by emergency physicians (EP) in resuscitation room of Accident and Emergency (A&E) Department
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Ong, YS, Cheung, KH, Graham, CA, Rainer, TH, and Cheung, NK
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- 2014
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41. MIRtazapine added to SSRIs or SNRIs for Treatment Resistant Depression in Primary Care: a placebo controlled randomised trial (MIR)
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Kessler, DS, MacNeil, SJ, Tallon, D, Lewis, G, Peters, TJ, Hollingworth, W, Round, J, Burns, A, Chew-Graham, CA, Anderson, IM, SHEPHERD, T, Campbell, J, Dickens, CM, Carter, M, Jenkinson, C, Macleod, U, Gibson, H, Davies, S, and Wiles, NJ
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R1 - Abstract
Objective: To investigate the effectiveness of combining mirtazapine with Serotonin-Noradrenaline Reuptake Inhibitor (SNRI) or Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants for patients in primary care who had not responded to an antidepressant.\ud \ud Design: A two parallel-group multi-centre, placebo controlled, randomised trial comparing the addition of mirtazapine to placebo for patients who had been adherent to an SSRI or SNRI for at least 6 weeks and were still depressed. Participants were stratified by centre and minimised by baseline Beck Depression Inventory score [BDI-II], gender and current psychological therapy. Participants, their General Practitioners (GPs), and the research team were blind to the allocation. Primary analyses compared the two groups as allocated without imputing missing data Setting: 106 general practices in 4 centres in the UK; Bristol, Exeter, Hull and North Staffordshire.\ud \ud Participants: Between August 2013 and October 2015, we recruited 480 participants aged over 17 years, 69.1% of whom were female. Participants scored >13 using the BDI-II and fulfilled International Classification of Diseases [ICD]-10 criteria for depression. Exclusion criteria included bipolar disorder, psychosis and major alcohol/substance abuse. 431 (89.8%) were included in the (primary) 12-week follow-up. \ud \ud Intervention: 241 participants were randomised to mirtazapine and 239 to placebo, both given in addition to their usual SSRI/SNRI medication. They were followed up at 12, 24 and 52 weeks. \ud Main outcome measures: Depressive symptoms at 12 weeks post-randomisation, measured using the BDI-II score as a continuous variable. Secondary outcomes include measures of anxiety, quality of life and adverse effects at 12, 24 and 52 weeks. \ud \ud Results: BDI-II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline BDI-II and minimisation/stratification variables, although the confidence interval included the null (mean (SD) BDI-II scores at 12 weeks: 18.0 (12.3) in the mirtazapine group; 19.7 (12.4) in the placebo group; adjusted difference between means -1.83 (95% confidence interval: -3.92 to 0.27, p=0.087)). Adverse effects were more frequent in the mirtazapine group and associated with stopping the trial medication.\ud \ud Conclusion: This study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI antidepressant over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where there is limited evidence of effective treatment options.
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- 2018
42. Preterm birth and maternal cardiovascular outcomes: a systematic review and meta-analysis
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Wu, P, Gulati, M, Kwok, CS, Wong, CW, Narain, A, O'Brien, SJ, Chew-Graham, CA, Verma, G, Kadam, UT, and Mamas, M
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RG ,RC666 ,R1 - Abstract
Background\ud Preterm delivery (
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- 2018
43. Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer
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Charlie Hatcher, George Richenberg, Samuel Waterson, Long H. Nguyen, Amit D. Joshi, Robert Carreras-Torres, Victor Moreno, Andrew T. Chan, Marc Gunter, Yi Lin, Conghui Qu, Mingyang Song, Graham Casey, Jane C. Figueiredo, Stephen B. Gruber, Jochen Hampe, Heather Hampel, Mark A. Jenkins, Temitope O. Keku, Ulrike Peters, Catherine M. Tangen, Anna H. Wu, David A. Hughes, Malte C. Rühlemann, Jeroen Raes, Nicholas J. Timpson, and Kaitlin H. Wade
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Medicine ,Science - Abstract
Abstract The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
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- 2023
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44. The Hexokinase 1 5′-UTR Mutation in Charcot–Marie–Tooth 4G Disease Alters Hexokinase 1 Binding to Voltage-Dependent Anion Channel-1 and Leads to Dysfunctional Mitochondrial Calcium Buffering
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Maria Ceprian, Raul Juntas-Morales, Graham Campbell, Ulrike Walther-Louvier, François Rivier, William Camu, Florence Esselin, Andoni Echaniz-Laguna, Tanya Stojkovic, Françoise Bouhour, Philippe Latour, and Nicolas Tricaud
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CMT4G ,mitochondria ,Hexokinase I ,VDAC ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Demyelinating Charcot–Marie–Tooth 4G (CMT4G) results from a recessive mutation in the 5′UTR region of the Hexokinase 1 (HK1) gene. HK participates in mitochondrial calcium homeostasis by binding to the Voltage-Dependent Anion Channel (VDAC), through its N-terminal porin-binding domain. Our hypothesis is that CMT4G mutation results in a broken interaction between mutant HK1 and VDAC, disturbing mitochondrial calcium homeostasis. We studied a cohort of 25 CMT4G patients recruited in the French gypsy population. The disease was characterized by a childhood onset, an intermediate demyelinating pattern, and a significant phenotype leading to becoming wheelchair-bound by the fifth decade of life. Co-IP and PLA studies indicated a strong decreased interaction between VDAC and HK1 in the patients' PBMCs and sural nerve. We observed that either wild-type HK1 expression or a peptide comprising the 15 aa of the N-terminal wild-type HK1 administration decreased mitochondrial calcium release in HEK293 cells. However, mutated CMT4G HK1 or the 15 aa of the mutated HK1 was unable to block mitochondrial calcium release. Taken together, these data show that the CMT4G-induced modification of the HK1 N-terminus disrupts HK1-VDAC interaction. This alters mitochondrial calcium buffering that has been shown to be critical for myelin sheath maintenance.
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- 2024
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45. Asthma among adult patients presenting with dyspnea to the emergency department: An observational study
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Kuan, WS, Craig, S, Kelly, A-M, Keijzers, G, Klim, S, Graham, CA, Jones, P, Holdgate, A, Lawoko, C, Laribi, S, Kuan, WS, Craig, S, Kelly, A-M, Keijzers, G, Klim, S, Graham, CA, Jones, P, Holdgate, A, Lawoko, C, and Laribi, S
- Abstract
INTRODUCTION: Shortness of breath is a common presenting symptom to the emergency department (ED) that can arise from a myriad of possible diagnoses. Asthma is one of the major causes. OBJECTIVE: The aim of this study was to describe the demographic features, clinical characteristics, management and outcomes of adults with an ED diagnosis of asthma who presented to an ED in the Asia Pacific region with a principal symptom of dyspnea. METHODS: Planned sub-study of patients with an ED diagnosis of asthma identified in the Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study. AANZDEM was a prospective cohort study conducted in 46 EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia over three 72 hour periods in May, August and October 2014. Primary outcomes were patient epidemiology, clinical features, treatment and outcomes (hospital length of stay (LOS) and mortality). RESULTS: Of the 3044 patients with dyspnea, 387 (12.7%) patients had an ED diagnosis of asthma. The median age was 45 years, 60.1% were female, 16.1% were active or recent smokers and 30.4% arrived by ambulance. Inhaled bronchodilator therapy was initiated in 88.1% of patients, and 66.9% received both inhaled bronchodilators and systemic corticosteroids. After treatment in the ED, 65.4% were discharged. No death was reported. CONCLUSION: Asthma is common among patients presenting with a principal symptom of dyspnea in the ED of the Asia Pacific region. There was a suboptimal adherence to international guidelines on investigations and treatments of acute asthma exacerbations presenting an opportunity to improve the efficiency of care.
- Published
- 2018
46. Epidemiology, treatment, disposition and outcome of patients with acute exacerbation of COPD presenting to emergency departments in Australia and South East Asia: An AANZDEM study
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Kelly, AM, Holdgate, A, Keijzers, G, Klim, S, Graham, CA, Craig, S, Kuan, WS, Jones, P, Lawoko, C, Laribi, S, Kelly, AM, Holdgate, A, Keijzers, G, Klim, S, Graham, CA, Craig, S, Kuan, WS, Jones, P, Lawoko, C, and Laribi, S
- Abstract
BACKGROUND AND OBJECTIVE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common presentation to emergency departments (ED) but data regarding its epidemiology and outcomes are scarce. We describe the epidemiology, clinical features, treatment and outcome of patients treated for AECOPD in ED. METHODS: This was a planned sub-study of patients with an ED diagnosis of AECOPD identified in the Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study. The AANZDEM was a prospective, interrupted time series cohort study conducted in 46 ED in Australia, New Zealand, Singapore, Hong Kong and Malaysia over three 72-h periods in May, August and October 2014. Primary outcomes were patient epidemiology, clinical features, treatment and outcomes (hospital length of stay (LOS) and mortality). RESULTS: Forty-six ED participated. There were 415 patients with an ED primary diagnosis of AECOPD (13.6% of the overall cohort; 95% CI: 12.5-14.9%). Median age was 73 years, 60% males and 65% arrived by ambulance. Ninety-one percent had an existing COPD diagnosis. Eighty percent of patients received inhaled bronchodilators, 66% received systemic corticosteroids and 57% of those with pH < 7.30 were treated with non-invasive ventilation (NIV). Seventy-eight percent of patients were admitted to hospital, 7% to an intensive care unit. In-hospital mortality was 4% and median LOS was 4 days (95% CI: 2-7). CONCLUSION: Patients treated in ED for AECOPD commonly arrive by ambulance, have a high admission rate and significant in-hospital mortality. Compliance with evidence-based treatments in ED is suboptimal affording an opportunity to improve care and potentially outcomes.
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- 2018
47. Author Correction: Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer
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Charlie Hatcher, George Richenberg, Samuel Waterson, Long H. Nguyen, Amit D. Joshi, Robert Carreras-Torres, Victor Moreno, Andrew T. Chan, Marc Gunter, Yi Lin, Conghui Qu, Mingyang Song, Graham Casey, Jane C. Figueiredo, Stephen B. Gruber, Jochen Hampe, Heather Hampel, Mark A. Jenkins, Temitope O. Keku, Ulrike Peters, Catherine M. Tangen, Anna H. Wu, David A. Hughes, Malte C. Rühlemann, Jeroen Raes, Nicholas J. Timpson, and Kaitlin H. Wade
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Medicine ,Science - Published
- 2023
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48. S02. Pre-Implantation Genetic Diagnosis (PGD) in Ireland - from validation to introduction of a clinical service
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Morrison, PJ, Campbell, E, Kennedy, F, Russell, A, Smithson, WH, Parsons, L, Liggan, B, Irwin, B, Delanty, N, Hunt, SJ, Craig, J, Morrow, J, Dineen, T, Zhang, X, Flanagan, J, Kovacs, A, Mihart, R, O'Callaghan, J, Culligan, J, Daly, N, Waterstone, J, Magee, AC, Stewart, FJ, Dabir, TA, McConachie, M, McCoubrey, A, McConnell, VPM, Stack, D, O'Meara, E, Phelan, S, McDonagh, N, Kelly, L, Sciot, R, Debiec-Rychter, M, Morris, T, Cochrane, D, Sorensen, P, O'Sullivan, MJ, O'Byrne, JJ, Sweeney, M, Donnelly, D, Lambert, D, Beattie, D, Gervin, C, Graham, CA, Barton, DE, Lynch, SA, Whelan, CD, Hibar, DP, Stein, JL, Speed, D, Sisodiya, S, Ohnson, M, Goldstein, D, Medland, SE, Ranke, B, Thompson, PM, Cavalleri, G, Coleman, C, Quinn, EM, Ryan, AW, Anney, RJL, Trimble, V, Morris, DW, Donohoe, G, Conroy, J, Trynka, G, Wijmenga, C, Ennis, S, McManus, R, O'Halloran, ET, Magalhaes, TR, Cole, A, Cox, S, Jeong, C, Witonsky, D, Robbins, P, Montgomery, H, Ota, M, Hanaoka, M, Droma, Y, Beall, CM, Rienzo, A Di, Casey, J, McGettigan, P, Crushell, E, Hughes, J, Smyth, LJ, Kilner, JK, Benson, KA, Maxwell, AP, McKnight, AJ, Donnelly, DE, Jeffers, L, Hampton, S, Baillie, N, Cooke, S, O'Connell, SM, McDonald, A, O'Toole, N, Bradfield, A, Bradley, M, Hattersley, A, Ellard, S, Proks, P, Mattis, KK, Ashcroft, F, O'Riordan, SMP, Coyle, D, McDermott, M, O'Sullivan, M, Roche, E, Quinn, F, Cody, D, MacMahon, JM, Morrissey, R, Green, A, Thompson, AR, Kulkarni, A, Marks, KJ, Snape, K, Taylor, R, Bradley, L, Ramachandrappa, S, Pinto, CF, Dabir, T, Logan, P, Liew, S., Znaczko, A, Ryan, H., McDevitt, T, Higgins, M, Crowley, A, Rogers, M, Geoghegan, S, Shorto, J, Ramsden, S, O'Riordan, MP, Moore, M, Murphy, M, Irvine, A, Znaczko, Anna, Wilson, A, Stewart, F, Cather, MH, Young, IS, Nicholls, DP, O'Kane, M, Sharpe, P, Hanna, E, Hart, PJ, Savage, N, Humphreys, MW, Shaw-Smith, C, Osio, D, Collinson, MN, McKee, S, McNerlan, S, McGorrian, C, Galvin, J, O'Byrne, J, Stewart, S, Heggarty, SV, Hegarty, SP, McConnell, V, Turner, J, Ward, A, Kelly, R, Joyce, C, ó hIcí, B, Meaney, K, Gibson, L, Kelly, PM, Costigan, C, Gul, R, Byrne, S, Hughes, L, Ozaki, M, O'Sullivan, F, Parle-McDermott, A, Heavin, SB, McCormack, M, Slattery, L, Walley, N, Avbersek, A, Novy, J, Sinha, S, S, Alarts, N, Legros, B, Radtke, R., Sisodiya, Depondt, C, Cavalleri, GL, Connolly, S, Heron, EA, Irvine, MAG, Hughes, AE, Darlow, JM, Darlay, R, Hunziker, M, Kutasy, B, Green, AJ, Cordell, H, Puri, P, Chand, S, McCaughan, JA, Shabir, S, Chan, W, Kilner, J, Borrows, R, Douglas, AP, O'Neill, T, Shepherd, C, Hardy, R, Kenny, Molloy, B, Freeley, M, Quinn, E, McGinn, R, Long, A, Gahan, JM, Connolly, E, Byrne, MM, Gray, SG, Murphy, RT, Gui, H, Heinzen, E, Goldstein, D B, Petrovski, S, O'Brien, TJ, Cherny, S, Sham, PC, Baum, L, Duffy, S, Catherwood, N, McVeigh, TP, Sweeney, KJ, Miller, N, Kerin, MJ, and Weidhaas, JB
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Poster Presentations ,Abstracts ,Spoken Papers - Published
- 2014
49. Sustaining cultures through cinematic space – the historical continuance of art and architectural traditions in 20 C Film
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Graham Cairns
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architecture ,film ,culture ,heritage ,Architecture ,NA1-9428 ,Building construction ,TH1-9745 - Abstract
This paper explores the idea of film as a medium that has been used to celebrate, develop and ultimately sustain cultural traditions in an age of globalization and technological and cultural change. It borrows ideas from the sector of heritage, namely intangible cultural heritage, and uses this to offer a framework for understanding the work of two key mid 20th century film directors, Jean Renoir and Yasujiro Ozu. Through a detailed analysis of the cinematography employed by both directors, their use of architectural space and the cultural traditions that they drew heavily upon, it explores examples how both directors used film as a medium for the reutilization of their particular cultural artistic traditions in a contemporary setting.
- Published
- 2022
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50. Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk
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Cameron B. Haas, Yu-Ru Su, Paneen Petersen, Xiaoliang Wang, Stephanie A. Bien, Yi Lin, Demetrius Albanes, Stephanie J. Weinstein, Mark A. Jenkins, Jane C. Figueiredo, Polly A. Newcomb, Graham Casey, Loic Le Marchand, Peter T. Campbell, Victor Moreno, John D. Potter, Lori C. Sakoda, Martha L. Slattery, Andrew T. Chan, Li Li, Graham G. Giles, Roger L. Milne, Stephen B. Gruber, Gad Rennert, Michael O. Woods, Steven J. Gallinger, Sonja Berndt, Richard B. Hayes, Wen-Yi Huang, Alicja Wolk, Emily White, Hongmei Nan, Rami Nassir, Noralane M. Lindor, Juan P. Lewinger, Andre E. Kim, David Conti, W. James Gauderman, Daniel D. Buchanan, Ulrike Peters, and Li Hsu
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Medicine ,Science - Abstract
Abstract Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene–environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case–control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E−4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E−4), and Aspartylglucosaminidase (AGA: p = 4.5E−4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.
- Published
- 2022
- Full Text
- View/download PDF
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