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2. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex, Saunders, Edward, Chen, Fei, Janivara, Rohini, Darst, Burcu, Sheng, Xin, Xu, Yili, Chou, Alisha, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark, Plym, Anna, Sahimi, Ali, Hoffman, Thomas, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy, Schleutker, Johanna, Tammela, Teuvo, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham, Southey, Melissa, MacInnis, Robert, Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher, Cho, Kelly, Mcmahon, Benjamin, Neal, David, Donovan, Jenny, Hamdy, Freddie, Martin, Richard, Nordestgaard, Borge, Nielsen, Sune, Weischer, Maren, Bojesen, Stig, Røder, Andreas, Stroomberg, Hein, Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith, Tilly, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison, Ghoussaini, Maya, Travis, Ruth, Key, Tim, Riboli, Elio, Park, Jong, Sellers, Thomas, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael, Mucci, Lorelei, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David, Penney, Kathryn, Turman, Constance, Tangen, Catherine, Goodman, Phyllis, Thompson, Ian, Hamilton, Robert, Fleshner, Neil, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet, Ostrander, Elaine, Koutros, Stella, Beane Freeman, Laura, Stampfer, Meir, Wolk, Alicja, and Håkansson, Niclas

Subjects
Humans, Male, Black People, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk Factors, White People, Asian People
Abstract

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Published
2023

3. Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy

Author

Cartwright, Emily J, Pierret, Chloe, Minassian, Caroline, Esserman, Denise A, Tate, Janet P, Goetz, Matthew B, Bhattacharya, Debika, Fiellin, David A, Justice, Amy C, Re, Vincent Lo, and Rentsch, Christopher T

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Clinical Research, Emerging Infectious Diseases, Infectious Diseases, Hepatitis, Chronic Liver Disease and Cirrhosis, Alcoholism, Alcohol Use and Health, Substance Misuse, Liver Disease, Hepatitis - C, Digestive Diseases, Infection, Good Health and Well Being, United States, Male, Humans, Middle Aged, Hepacivirus, Antiviral Agents, Alcoholism, Hepatitis C, Chronic, Sustained Virologic Response, Cohort Studies, Retrospective Studies, Hepatitis C, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceSome payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection.ObjectiveTo evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR).Design, setting, and participantsThis retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023.ExposureAlcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.Main outcomes and measuresThe primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category.ResultsAmong 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30).Conclusions and relevanceIn this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

Published
2023

4. A multi-ancestry genetic study of pain intensity in 598,339 veterans

Author

Toikumo, Sylvanus, Vickers-Smith, Rachel, Jinwala, Zeal, Xu, Heng, Saini, Divya, Hartwell, Emily E., Pavicic, Mirko, Sullivan, Kyle A., Xu, Ke, Jacobson, Daniel A., Gelernter, Joel, Rentsch, Christopher T., Stahl, Eli, Cheatle, Martin, Zhou, Hang, Waxman, Stephen G., Justice, Amy C., Kember, Rachel L., and Kranzler, Henry R.

Published
2024
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5. Dyadic Characteristics and Intimate Partner Violence among Men Who Have Sex with Men

Author

Stephenson, Robert, Rentsch, Christopher, Salazar, Laura, and Sullivan, Patrick

Subjects
IPV, MSM, Relationships, Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Objective: Although the research community has begun to recognize intimate partner violence (IPV) as an important issue in same-sex relationships, there has been a lack of attention to characteristics of these relationships that may be associated with IPV. In particular, there has been a lack of attention paid to the associations between dyadic characteristics and IPV in same-sex relationships. This paper examined associations between dyadic characteristics, including relationship satisfaction, communal coping and efficacy, and perpetrating and experiencing IPV among a sample of United States men who have sex with men (MSM). Methods: We collected data via an online survey with 528 MSM, who were greater than 18 years of age and reported at least one male sex partner in the last 12 months. The analysis examined dyadic factors associated with reporting of experiencing and perpetrating emotional violence, physical violence, and sexual violence. Results: The prevalence of violence in the sample ranged from nine percent reporting perpetrating sexual violence to 33% of men reporting experiencing emotional violence. MSM who reported greater satisfaction with their relationship or who reported a higher degree of concordance with their partner on lifestyle choices were less likely to report experiencing or perpetrating emotional violence. MSM who perceived a stigma to being in a male same-sex couple were less likely to report experiencing or perpetrating sexual violence. Conclusion: The results presented here demonstrate high levels of IPV among MSM and that dyadic characteristics are associated with the occurrence of IPV. Understanding relationship characteristics associated with increased IPV among same-sex male couples can contribute to the development of more accurate IPV screening tools, and more sensitively and appropriately designed intervention messages. [West J Emerg Med. 2011;12(3):324-332.]

Published
2011

6. Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction

Author

Kember, Rachel L, Vickers-Smith, Rachel, Xu, Heng, Toikumo, Sylvanus, Niarchou, Maria, Zhou, Hang, Hartwell, Emily E, Crist, Richard C, Rentsch, Christopher T, Davis, Lea K, Justice, Amy C, Sanchez-Roige, Sandra, Kampman, Kyle M, Gelernter, Joel, and Kranzler, Henry R

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Biotechnology, Drug Abuse (NIDA only), Human Genome, Genetics, Neurosciences, Substance Misuse, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Behavior, Addictive, Brain, Furin, Genome-Wide Association Study, Humans, Opioid-Related Disorders, Million Veteran Program, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Despite an estimated heritability of ~50%, genome-wide association studies of opioid use disorder (OUD) have revealed few genome-wide significant loci. We conducted a cross-ancestry meta-analysis of OUD in the Million Veteran Program (N = 425,944). In addition to known exonic variants in OPRM1 and FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1 and KCNN1. A meta-analysis including other datasets identified a locus in TSNARE1. In total, we identified 14 loci for OUD, 12 of which are novel. Significant genetic correlations were identified for 127 traits, including psychiatric disorders and other substance use-related traits. The only significantly enriched cell-type group was CNS, with gene expression enrichment in brain regions previously associated with substance use disorders. These findings increase our understanding of the biological basis of OUD and provide further evidence that it is a brain disease, which may help to reduce stigma and inform efforts to address the opioid epidemic.

Published
2022

7. Care interruptions and mortality among adults in Europe and North America

Author

Trickey, Adam, Zhang, Lei, Rentsch, Christopher T., Pantazis, Nikos, Izquierdo, Rebeca, Antinori, Andrea, Leierer, Gisela, Burkholder, Greer, Cavassini, Matthias, Palacio-Vieira, Jorge, Gill, M. John, Teira, Ramon, Stephan, Christoph, Obel, Niels, Vehreschild, Jorg-Janne, Sterling, Timothy R., Van Der Valk, Marc, Bonnet, Fabrice, Crane, Heidi M., Silverberg, Michael J., Ingle, Suzanne M., and Sterne, Jonathan A.C.

Published
2024
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8. Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support

Author

Crothers, Kristina, DeFaccio, Rian, Tate, Janet, Alba, Patrick R, Goetz, Matthew Bidwell, Jones, Barbara, King, Joseph T, Marconi, Vincent, Ohl, Michael E, Rentsch, Christopher T, Rodriguez-Barradas, Maria C, Shahrir, Shahida, Justice, Amy C, and Akgün, Kathleen M

Subjects
Lung, Good Health and Well Being, Aged, Dexamethasone, Female, Hospitalization, Humans, Male, SARS-CoV-2, COVID-19 Drug Treatment, Veterans Aging Cohort Study Clinical COVID-19 Working Group, Medical and Health Sciences, Respiratory System
Abstract

BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.MethodsWe included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.ResultsOf 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36).ConclusionsIn patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.

Published
2022

9. Clinical coding of long COVID in primary care 2020–2023 in a cohort of 19 million adults: an OpenSAFELY analysis

Author

Walker, Alex, Green, Amelia, Mehrkar, Amir, Schaffer, Andrea, Brown, Andrew, Goldacre, Ben, Butler-Cole, Ben, MacKenna, Brian, Morton, Caroline, Walters, Caroline, Stables, Catherine, Cunningham, Christine, Wood, Christopher, Andrews, Colm, Evans, David, Hickman, George, Curtis, Helen, Drysdale, Henry, Dillingham, Iain, Morley, Jessica, Massey, Jon, Nab, Linda, Hopcroft, Lisa, Fisher, Louis, Bridges, Lucy, Wiedemann, Milan, DeVito, Nicholas, Macdonald, Orla, Inglesby, Peter, Smith, Rebecca, Croker, Richard, Park, Robin, Higgins, Rose, Bacon, Sebastian, Davy, Simon, Maude, Steven, O'Dwyer, Thomas, Ward, Tom, Speed, Victoria, Hulme, William, Hart, Liam, Stokes, Pete, Bhaskaran, Krishnan, Costello, Ruth, Cowling, Thomas, Douglas, Ian, Eggo, Rosalind, Evans, Stephen, Forbes, Harriet, Grieve, Richard, Grint, Daniel, Herrett, Emily, Langan, Sinead, Mahalingasivam, Viyaasan, Mansfield, Kathryn, Mathur, Rohini, McDonald, Helen, Parker, Edward, Rentsch, Christopher, Schultze, Anna, Smeeth, Liam, Tazare, John, Tomlinson, Laurie, Walker, Jemma, Williamson, Elizabeth, Wing, Kevin, Wong, Angel, Zheng, Bang, Bates, Christopher, Cockburn, Jonathan, Parry, John, Hester, Frank, Harper, Sam, O'Hanlon, Shaun, Eavis, Alex, Jarvis, Richard, Avramov, Dima, Griffiths, Paul, Fowles, Aaron, Parkes, Nasreen, Perera, Rafael, Harrison, David, Khunti, Kamlesh, Sterne, Jonathan, Quint, Jennifer, Henderson, Alasdair D., Butler-Cole, Ben FC., Tomlinson, Laurie A., Marks, Michael, Jit, Mark, Briggs, Andrew, Lin, Liang-Yu, Carlile, Oliver, Bates, Chris, Bacon, Sebastian CJ., Dennison, William A., Costello, Ruth E., Wei, Yinghui, Walker, Alex J., and Eggo, Rosalind M.

Published
2024
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10. Impact of long COVID on health-related quality-of-life: an OpenSAFELY population cohort study using patient-reported outcome measures (OpenPROMPT)

Author

Walker, Alex, Green, Amelia, Mehrkar, Amir, Schaffer, Andrea, Brown, Andrew, Goldacre, Ben, Butler-Cole, Ben, MacKenna, Brian, Morton, Caroline, Walters, Caroline, Stables, Catherine, Cunningham, Christine, Wood, Christopher, Andrews, Colm, Evans, David, Hickman, George, Curtis, Helen, Drysdale, Henry, Dillingham, Iain, Morley, Jessica, Massey, Jon, Nab, Linda, Hopcroft, Lisa, Fisher, Louis, Bridges, Lucy, Wiedemann, Milan, DeVito, Nicholas, Macdonald, Orla, Inglesby, Peter, Smith, Rebecca, Croker, Richard, Park, Robin, Higgins, Rose, Bacon, Sebastian, Davy, Simon, Maude, Steven, O'Dwyer, Thomas, Ward, Tom, Speed, Victoria, Hulme, William, Hart, Liam, Stokes, Pete, Bhaskaran, Krishnan, Costello, Ruth, Cowling, Thomas, Douglas, Ian, Eggo, Rosalind, Evans, Stephen, Forbes, Harriet, Grieve, Richard, Grint, Daniel, Herrett, Emily, Langan, Sinead, Mahalingasivam, Viyaasan, Mansfield, Kathryn, Mathur, Rohini, McDonald, Helen, Parker, Edward, Rentsch, Christopher, Schultze, Anna, Smeeth, Liam, Tazare, John, Tomlinson, Laurie, Walker, Jemma, Williamson, Elizabeth, Wing, Kevin, Wong, Angel, Zheng, Bang, Bates, Christopher, Cockburn, Jonathan, Parry, John, Hester, Frank, Harper, Sam, O'Hanlon, Shaun, Eavis, Alex, Jarvis, Richard, Avramov, Dima, Griffiths, Paul, Fowles, Aaron, Parkes, Nasreen, Perera, Rafael, Harrison, David, Khunti, Kamlesh, Sterne, Jonathan, Quint, Jennifer, Carlile, Oliver, Briggs, Andrew, Henderson, Alasdair D., Butler-Cole, Ben F.C., Tomlinson, Laurie A., Marks, Michael, Jit, Mark, Lin, Liang-Yu, Bates, Chris, Bacon, Sebastian C.J., Dennison, William A., Costello, Ruth E., Walker, Alex J., and Eggo, Rosalind M.

Published
2024
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11. Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration

Author

Rein, Sophia M, Lodi, Sara, Logan, Roger W, Touloumi, Giota, Antoniadou, Anastasia, Wittkop, Linda, Bonnet, Fabrice, van Sighem, Ard, van der Valk, Marc, Reiss, Peter, Klein, Marina B, Young, James, Jarrin, Inmaculada, d'Arminio Monforte, Antonella, Tavelli, Alessandro, Meyer, Laurence, Tran, Laurent, Gill, Michael J, Lang, Raynell, Surial, Bernard, Haas, Andreas D, Justice, Amy C, Rentsch, Christopher T, Phillips, Andrew, Sabin, Caroline A, Miro, Jose M, Trickey, Adam, Ingle, Suzanne M, Sterne, Jonathan A C, and Hernán, Miguel A

Published
2023
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14. Statin exposure and risk of cancer in people with and without HIV infection.

Author

Bedimo, Roger J, Park, Lesley S, Shebl, Fatima M, Sigel, Keith, Rentsch, Christopher T, Crothers, Kristina, Rodriguez-Barradas, Maria C, Goetz, Matthew Bidwell, Butt, Adeel A, Brown, Sheldon T, Gibert, Cynthia, Justice, Amy C, and Tate, Janet P

Subjects
Clinical Research, HIV/AIDS, Prevention, Cancer, Infectious Diseases, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Cohort Studies, Female, HIV Infections, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Neoplasms, Proportional Hazards Models, cancer, HIV, hypolipidemic agents, neoplasms, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology
Abstract

ObjectiveTo determine whether statin exposure is associated with decreased cancer and mortality risk among persons with HIV (PWH) and uninfected persons. Statins appear to have immunomodulatory and anti-inflammatory effects and may reduce cancer risk, particularly among PWH as they experience chronic inflammation and immune activation.DesignPropensity score-matched cohort of statin-exposed and unexposed patients from 2002 to 2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data.MethodsWe calculated Cox regression hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, microbial cancers (associated with bacterial or oncovirus coinfection), nonmicrobial cancers, and mortality.Results:The propensity score-matched sample (N = 47 940) included 23 970 statin initiators (31% PWH). Incident cancers were diagnosed in 1160 PWH and 2116 uninfected patients. Death was reported in 1667 (7.0%) statin-exposed, and 2215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial-associated cancers (hazard ratio 0.76; 95% CI 0.69-0.85), but was not associated with nonmicrobial cancer risk (hazard ratio 1.00; 95% CI 0.92-1.09). Statin use was associated with 33% lower risk of death overall (hazard ratio 0.67; 95% CI 0.63-0.72). Results were similar in analyses stratified by HIV status, except for non-Hodgkin lymphoma where statin use was associated with reduced risk (hazard ratio 0.56; 95% CI 0.38-0.83) for PWH, but not for uninfected (P interaction = 0.012).ConclusionIn both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not nonmicrobial cancer incidence, and with decreased mortality.

Published
2021

15. Radiative forcing by CO$_2$ observed at top of atmosphere from 2002-2019

Author

Rentsch, Christopher

Subjects
Physics - Atmospheric and Oceanic Physics
Abstract

Spectroscopic measurements at top of atmosphere are uniquely capable of attributing changes in Earth's outgoing infrared radiation field to specific greenhouse gasses. The Atmospheric Infrared Sounder (AIRS) placed in orbit in 2002 has spectroscopically resolved a portion of Earth's outgoing longwave radiation for over 17 years. Concurrently, atmospheric CO$_2$ rose from 373 to 410 ppm, or 28% of the total increase over pre-industrial levels. The Coupled Model Intercomparison Project Phase 6 (CMIP6) multi-model ensemble average predicts 0.477 Wm$^{-2}$ clear-sky longwave effective radiative forcing from this increase. Global measurements under nighttime, clear-sky conditions reveal 0.360$\pm$0.026 Wm$^{-2}$ of CO$_2$-induced longwave radiative forcing, or 75$\pm$5% of model predictions., Comment: 11 pages, 8 figures, no external funding

Published
2019

16. Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform

Author

Chaturvedi, Nishi, Park, Chloe, Carnemolla, Alisia, Williams, Dylan, Knueppel, Anika, Boyd, Andy, Turner, Emma L., Evans, Katharine M., Thomas, Richard, Berman, Samantha, McLachlan, Stela, Crane, Matthew, Whitehorn, Rebecca, Oakley, Jacqui, Foster, Diane, Woodward, Hannah, Campbell, Kirsteen C., Timpson, Nicholas, Kwong, Alex, Soares, Ana Goncalves, Griffith, Gareth, Toms, Renin, Jones, Louise, Annie, Herbert, Mitchell, Ruth, Palmer, Tom, Sterne, Jonathan, Walker, Venexia, Huntley, Lizzie, Fox, Laura, Denholm, Rachel, Knight, Rochelle, Northstone, Kate, Kanagaratnam, Arun, Horne, Elsie, Forbes, Harriet, North, Teri, Taylor, Kurt, Arab, Marwa A.L., Walker, Scott, Coronado, Jose I.C., Karthikeyan, Arun S., Ploubidis, George, Moltrecht, Bettina, Booth, Charlotte, Parsons, Sam, Wielgoszewska, Bozena, Bridger-Staatz, Charis, Steves, Claire, Thompson, Ellen, Garcia, Paz, Cheetham, Nathan, Bowyer, Ruth, Freydin, Maxim, Roberts, Amy, Goldacre, Ben, Walker, Alex, Morley, Jess, Hulme, William, Nab, Linda, Fisher, Louis, MacKenna, Brian, Andrews, Colm, Curtis, Helen, Hopcroft, Lisa, Green, Amelia, Patalay, Praveetha, Maddock, Jane, Patel, Kishan, Stafford, Jean, Jacques, Wels, Tilling, Kate, Macleod, John, McElroy, Eoin, Shah, Anoop, Silverwood, Richard, Denaxas, Spiros, Flaig, Robin, McCartney, Daniel, Campbell, Archie, Tomlinson, Laurie, Tazare, John, Zheng, Bang, Smeeth, Liam, Herrett, Emily, Cowling, Thomas, Mansfield, Kate, Costello, Ruth E., Wang, Kevin, Mansfield, Kathryn, Mahalingasivam, Viyaasan, Douglas, Ian, Langan, Sinead, Brophy, Sinead, Parker, Michael, Kennedy, Jonathan, McEachan, Rosie, Wright, John, Willan, Kathryn, Badrick, Ellena, Santorelli, Gillian, Yang, Tiffany, Hou, Bo, Steptoe, Andrew, Giorgio, Di Gessa, Zhu, Jingmin, Zaninotto, Paola, Wood, Angela, Cezard, Genevieve, Ip, Samantha, Bolton, Tom, Sampri, Alexia, Rafeti, Elena, Almaghrabi, Fatima, Sheikh, Aziz, Shah, Syed A., Katikireddi, Vittal, Shaw, Richard, Hamilton, Olivia, Green, Michael, Kromydas, Theocharis, Kopasker, Daniel, Greaves, Felix, Willans, Robert, Glen, Fiona, Sharp, Steve, Hughes, Alun, Wong, Andrew, Howes, Lee Hamill, Rapala, Alicja, Nigrelli, Lidia, McArdle, Fintan, Beckford, Chelsea, Raman, Betty, Dobson, Richard, Folarin, Amos, Stewart, Callum, Ranjan, Yatharth, Carpentieri, Jd, Sheard, Laura, Fang, Chao, Baz, Sarah, Gibson, Andy, Kellas, John, Neubauer, Stefan, Piechnik, Stefan, Lukaschuk, Elena, Saunders, Laura C., Wild, James M., Smith, Stephen, Jezzard, Peter, Tunnicliffe, Elizabeth, Sanders, Zeena-Britt, Finnigan, Lucy, Ferreira, Vanessa, Green, Mark, Rhead, Rebecca, Kibble, Milla, Wei, Yinghui, Lemanska, Agnieszka, Perez-Reche, Francisco, Piehlmaier, Dominik, Teece, Lucy, Parker, Edward, Walker, Alex J., Inglesby, Peter, Curtis, Helen J., Morton, Caroline E., Morley, Jessica, Mehrkar, Amir, Bacon, Sebastian C.J., Hickman, George, Croker, Richard, Evans, David, Ward, Tom, DeVito, Nicholas J., Green, Amelia C.A., Massey, Jon, Smith, Rebecca M., Hulme, William J., Davy, Simon, Andrews, Colm D., Hopcroft, Lisa E.M., Drysdale, Henry, Dillingham, Iain, Park, Robin Y., Higgins, Rose, Cunningham, Christine, Wiedemann, Milan, Maude, Steven, Macdonald, Orla, Butler-Cole, Ben F.C., O'Dwyer, Thomas, Stables, Catherine L., Wood, Christopher, Brown, Andrew D., Speed, Victoria, Bridges, Lucy, Schaffer, Andrea L., Walters, Caroline E., Rentsch, Christopher T., Bhaskaran, Krishnan, Schultze, Anna, Williamson, Elizabeth J., McDonald, Helen I., Tomlinson, Laurie A., Mathur, Rohini, Eggo, Rosalind M., Wing, Kevin, Wong, Angel Y.S., Grieve, Richard, Grint, Daniel J., Mansfield, Kathryn E., Douglas, Ian J., Evans, Stephen J.W., Walker, Jemma L., Cowling, Thomas E., Herrett, Emily L., Parker, Edward P.K., Bates, Christopher, Cockburn, Jonathan, Parry, John, Hester, Frank, Harper, Sam, O'Hanlon, Shaun, Eavis, Alex, Jarvis, Richard, Avramov, Dima, Griffiths, Paul, Fowles, Aaron, Parkes, Nasreen, Nicholson, Brian, Perera, Rafael, Harrison, David, Khunti, Kamlesh, Sterne, Jonathan AC., Quint, Jennifer, Henderson, Alasdair D., Carreira, Helena, Bidulka, Patrick, Warren-Gash, Charlotte, Hayes, Joseph F., Quint, Jennifer K., Katikireddi, Srinivasa Vittal, and Langan, Sinéad M.

Published
2023
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17. Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Author

Chen, Fei, Madduri, Ravi K., Rodriguez, Alex A., Darst, Burcu F., Chou, Alisha, Sheng, Xin, Wang, Anqi, Shen, Jiayi, Saunders, Edward J., Rhie, Suhn K., Bensen, Jeannette T., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Stanford, Janet L., Zheng, Wei, Sanderson, Maureen, John, Esther M., Park, Jong Y., Xu, Jianfeng, Wang, Ying, Berndt, Sonja I., Huff, Chad D., Yeboah, Edward D., Tettey, Yao, Lachance, Joseph, Tang, Wei, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A., Yamoah, Kosj, Murphy, Adam B., Crawford, Dana C., Patel, Alpa V., Bush, William S., Aldrich, Melinda C., Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine M., Stern, Mariana C., Kote-Jarai, Zsofia, Govindasami, Koveela, Cook, Michael B., Chokkalingam, Anand P., Hsing, Ann W., Goodman, Phyllis J., Hoffmann, Thomas J., Drake, Bettina F., Hu, Jennifer J., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Idowu, Michael O., Popoola, Olufemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Mensah, James E., Diop, Halimatou, Van Den Eeden, Stephen K., Blanchet, Pascal, Fowke, Jay H., Casey, Graham, Hennis, Anselm J., Lubwama, Alexander, Thompson, Ian M., Jr., Leach, Robin, Easton, Douglas F., Preuss, Michael H., Loos, Ruth J., Gundell, Susan M., Wan, Peggy, Mohler, James L., Fontham, Elizabeth T., Smith, Gary J., Taylor, Jack A., Srivastava, Shiv, Eeles, Rosaline A., Carpten, John D., Kibel, Adam S., Multigner, Luc, Parent, Marie-Élise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A., Andrews, Caroline, Rebbeck, Timothy R., Brureau, Laurent, Ambs, Stefan, Edwards, Todd L., Watya, Stephen, Chanock, Stephen J., Witte, John S., Blot, William J., Michael Gaziano, J., Justice, Amy C., Conti, David V., and Haiman, Christopher A.

Published
2023
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18. Association of OPRM1 Functional Coding Variant With Opioid Use Disorder

Author

Zhou, Hang, Rentsch, Christopher T, Cheng, Zhongshan, Kember, Rachel L, Nunez, Yaira Z, Sherva, Richard M, Tate, Janet P, Dao, Cecilia, Xu, Ke, Polimanti, Renato, Farrer, Lindsay A, Justice, Amy C, Kranzler, Henry R, and Gelernter, Joel

Subjects
Human Genome, Brain Disorders, Substance Misuse, Genetics, Drug Abuse (NIDA only), Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Aged, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Opioid-Related Disorders, Receptors, Opioid, mu, United States, United States Department of Veterans Affairs, Neurosciences, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Biotechnology, Pediatric, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Animals, Autism Spectrum Disorder, Brain, Cerebral Cortex, Epigenesis, Genetic, Epigenomics, Evolution, Molecular, Gene Expression, Histone Code, Interneurons, Macaca mulatta, Neurons, Pan troglodytes, Primates, Regulatory Elements, Transcriptional, Regulatory Sequences, Nucleic Acid, Transcriptome, H3K27ac histone modification, regulatory elements, glutamatergic neurons, GABAergic neurons, primate evolution, Other Medical and Health Sciences, Psychology, Cognitive Sciences
Abstract

The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type-specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype-specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergoes subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type-dependent gene-expression programs, and provides a resource for further exploration of human brain evolution and function.

Published
2020

20. Medical Intensive Care Unit Admission Among Patients With and Without HIV, Hepatitis C Virus, and Alcohol-Related Diagnoses in the United States

Author

Rentsch, Christopher T, Tate, Janet P, Steel, Tessa, Butt, Adeel A, Gibert, Cynthia L, Huang, Laurence, Pisani, Margaret, Soo Hoo, Guy W, Crystal, Stephen, Rodriguez-Barradas, Maria C, Brown, Sheldon T, Freiberg, Matthew S, Graber, Christopher J, Kim, Joon W, Rimland, David, Justice, Amy C, Fiellin, David A, Crothers, Kristina A, and Akgün, Kathleen M

Subjects
Liver Disease, Hepatitis - C, Hepatitis, Chronic Liver Disease and Cirrhosis, HIV/AIDS, Infectious Diseases, Substance Misuse, Digestive Diseases, Clinical Research, Alcoholism, Alcohol Use and Health, Emerging Infectious Diseases, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Adult, Alcohol Drinking, Alcohol-Related Disorders, Coinfection, Female, HIV Infections, Hepatitis C, Humans, Intensive Care Units, Male, Middle Aged, Patient Admission, Retrospective Studies, Risk Factors, United States, intensive care units, HIV, hepatitis C, alcoholism, electronic health records, veterans, Clinical Sciences, Public Health and Health Services, Virology
Abstract

BackgroundHIV, hepatitis C virus (HCV), and alcohol-related diagnoses (ARD) independently contribute increased risk of all-cause hospitalization. We sought to determine annual medical intensive care unit (MICU) admission rates and relative risk of MICU admission between 1997 and 2014 among people with and without HIV, HCV, and ARD, using data from the largest HIV and HCV care provider in the United States.SettingVeterans Health Administration.MethodsAnnual MICU admission rates were calculated among 155,550 patients in the Veterans Aging Cohort Study by HIV, HCV, and ARD status. Adjusted rate ratios and 95% confidence intervals (CIs) were estimated with Poisson regression. Significance of trends in age-adjusted admission rates were tested with generalized linear regression. Models were stratified by calendar period to identify shifts in MICU admission risk over time.ResultsCompared to HIV-/HCV-/ARD- patients, relative risk of MICU admission decreased among HIV-mono-infected patients from 61% (95% CI: 1.56 to 1.65) in 1997-2009% to 21% (95% CI: 1.16 to 1.27) in 2010-2014, increased among HCV-mono-infected patients from 22% (95% CI: 1.16 to 1.29) in 1997-2009% to 54% (95% CI: 1.43 to 1.67) in 2010-2014, and remained consistent among patients with ARD only at 46% (95% CI: 1.42 to 1.50). MICU admission rates decreased by 48% among HCV-uninfected patients (P-trend

Published
2019

21. Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform

Author

MacKenna, Brian, Kennedy, Nicholas A, Mehrkar, Amir, Rowan, Anna, Galloway, James, Matthewman, Julian, Mansfield, Kathryn E, Bechman, Katie, Yates, Mark, Brown, Jeremy, Schultze, Anna, Norton, Sam, Walker, Alex J, Morton, Caroline E, Harrison, David, Bhaskaran, Krishnan, Rentsch, Christopher T, Williamson, Elizabeth, Croker, Richard, Bacon, Seb, Hickman, George, Ward, Tom, Davy, Simon, Green, Amelia, Fisher, Louis, Hulme, William, Bates, Chris, Curtis, Helen J, Tazare, John, Eggo, Rosalind M, Evans, David, Inglesby, Peter, Cockburn, Jonathan, McDonald, Helen I, Tomlinson, Laurie A, Mathur, Rohini, Wong, Angel Y S, Forbes, Harriet, Parry, John, Hester, Frank, Harper, Sam, Douglas, Ian J, Smeeth, Liam, Lees, Charlie W, Evans, Stephen J W, Goldacre, Ben, Smith, Catherine H, and Langan, Sinéad M

Published
2022
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22. Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study

Author

Trickey, Adam, Zhang, Lei, Gill, M John, Bonnet, Fabrice, Burkholder, Greer, Castagna, Antonella, Cavassini, Matthias, Cichon, Piotr, Crane, Heidi, Domingo, Pere, Grabar, Sophie, Guest, Jodie, Obel, Niels, Psichogiou, Mina, Rava, Marta, Reiss, Peter, Rentsch, Christopher T, Riera, Melchor, Schuettfort, Gundolf, Silverberg, Michael J, Smith, Colette, Stecher, Melanie, Sterling, Timothy R, Ingle, Suzanne M, Sabin, Caroline A, and Sterne, Jonathan A C

Published
2022
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25. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records

Author

Thompson, Ellen J., Williams, Dylan M., Walker, Alex J., Mitchell, Ruth E., Niedzwiedz, Claire L., Yang, Tiffany C., Huggins, Charlotte F., Kwong, Alex S. F., Silverwood, Richard J., Di Gessa, Giorgio, Bowyer, Ruth C. E., Northstone, Kate, Hou, Bo, Green, Michael J., Dodgeon, Brian, Doores, Katie J., Duncan, Emma L., Williams, Frances M. K., Steptoe, Andrew, Porteous, David J., McEachan, Rosemary R. C., Tomlinson, Laurie, Goldacre, Ben, Patalay, Praveetha, Ploubidis, George B., Katikireddi, Srinivasa Vittal, Tilling, Kate, Rentsch, Christopher T., Timpson, Nicholas J., Chaturvedi, Nishi, and Steves, Claire J.

Published
2022
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26. Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: a cohort study from OpenSAFELY

Author

Green, Amelia, Curtis, Helen, Hulme, William, Williamson, Elizabeth, McDonald, Helen, Bhaskaran, Krishnan, Rentsch, Christopher, Schultze, Anna, MacKenna, Brian, Mahalingasivam, Viyaasan, Tomlinson, Laurie, Walker, Alex, Fisher, Louis, Massey, Jon, Andrews, Colm, Hopcroft, Lisa, Morton, Caroline, Croker, Richard, Morley, Jessica, Mehrkar, Amir, Bacon, Seb, Evans, David, Inglesby, Peter, Hickman, George, Ward, Tom, Davy, Simon, Mathur, Rohini, Tazare, John, Eggo, Rosalind, Wing, Kevin, Wong, Angel, Forbes, Harriet, Bates, Chris, Cockburn, Jonathan, Parry, John, Hester, Frank, Harper, Sam, Douglas, Ian, Evans, Stephen, Smeeth, Liam, and Goldacre, Ben

Published
2022
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27. Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform

Author

Williamson, Elizabeth J., Tazare, John, Bhaskaran, Krishnan, McDonald, Helen I., Walker, Alex J., Tomlinson, Laurie, Wing, Kevin, Bacon, Sebastian, Bates, Chris, Curtis, Helen J., Forbes, Harriet J., Minassian, Caroline, Morton, Caroline E., Nightingale, Emily, Mehrkar, Amir, Evans, David, Nicholson, Brian D., Leon, David A., Inglesby, Peter, MacKenna, Brian, Davies, Nicholas G., DeVito, Nicholas J., Drysdale, Henry, Cockburn, Jonathan, Hulme, William J., Morley, Jessica, Douglas, Ian, Rentsch, Christopher T., Mathur, Rohini, Wong, Angel, Schultze, Anna, Croker, Richard, Parry, John, Hester, Frank, Harper, Sam, Grieve, Richard, Harrison, David A., Steyerberg, Ewout W., Eggo, Rosalind M., Diaz-Ordaz, Karla, Keogh, Ruth, Evans, Stephen J. W., Smeeth, Liam, and Goldacre, Ben

Published
2022
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30. Core Concepts in Pharmacoepidemiology: Quantitative Bias Analysis.

Author

Brown, Jeremy P., Hunnicutt, Jacob N., Ali, M. Sanni, Bhaskaran, Krishnan, Cole, Ashley, Langan, Sinead M., Nitsch, Dorothea, Rentsch, Christopher T., Galwey, Nicholas W., Wing, Kevin, and Douglas, Ian J.

Abstract

Pharmacoepidemiological studies provide important information on the safety and effectiveness of medications, but the validity of study findings can be threatened by residual bias. Ideally, biases would be minimized through appropriate study design and statistical analysis methods. However, residual biases can remain, for example, due to unmeasured confounders, measurement error, or selection into the study. A group of sensitivity analysis methods, termed quantitative bias analyses, are available to assess, quantitatively and transparently, the robustness of study results to these residual biases. These approaches include methods to quantify how the estimated effect would be altered under specified assumptions about the potential bias, and methods to calculate bounds on effect estimates. This article introduces quantitative bias analyses for unmeasured confounding, misclassification, and selection bias, with a focus on their relevance and application to pharmacoepidemiological studies. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Provider verification of electronic health record receipt and nonreceipt of direct-acting antivirals for the treatment of hepatitis C virus infection

Author

Rentsch, Christopher T, Cartwright, Emily J, Gandhi, Neel R, Brown, Sheldon T, Rodriguez-Barradas, Maria C, Goetz, Matthew Bidwell, Marconi, Vincent C, Gibert, Cynthia L, Re, Vincent Lo, Fiellin, David A, Justice, Amy C, and Tate, Janet P

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Emerging Infectious Diseases, Infectious Diseases, Clinical Research, Hepatitis, Hepatitis - C, Liver Disease, Infection, Good Health and Well Being, Aged, Antiviral Agents, Drug Prescriptions, Electronic Health Records, Female, Hepatitis C, Chronic, Humans, Male, Middle Aged, Pharmacoepidemiology, Pharmacy, United States, United States Department of Veterans Affairs, Veterans, Veterans Health, Antivirals, Direct-acting antiviral, Hepatitis C, Observational data, Validation, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

PurposePharmacoepidemiologic studies using electronic health record data could serve an important role in assessing safety and effectiveness of direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity of these data needs to be determined. We evaluated the accuracy of pharmacy fill records in the national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) as compared to facility-level electronic health record.MethodsPatients prescribed a direct-acting antiviral regimen at five VA sites between 2014 and 2016 were randomly selected and reviewed. A random sample of patients with chronic HCV infection without evidence of HCV treatment during the study period also underwent chart review. We calculated positive predictive value and negative predictive value overall and by site.ResultsOf the 501 patients who received a total of 2416 prescriptions, 494 were validated using data extracted from CDW 6 months after the study period, yielding a positive predictive value of 98.6% (95% confidence interval, 97.6%-99.6%). Of the 100 patients with chronic HCV infection without prescriptions for HCV treatment, 99 were confirmed not to have received antiviral treatment (negative predictive value, 99.0%; 95% confidence interval, 97.1%-100%).ConclusionsThese findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information on HCV therapies in the modern treatment era.

Published
2018

32. OpenSAFELY: A platform for analysing electronic health records designed for reproducible research

Author

Nab, Linda, primary, Schaffer, Andrea L., additional, Hulme, William, additional, DeVito, Nicholas J., additional, Dillingham, Iain, additional, Wiedemann, Milan, additional, Andrews, Colm D., additional, Curtis, Helen, additional, Fisher, Louis, additional, Green, Amelia, additional, Massey, Jon, additional, Walters, Caroline E., additional, Higgins, Rose, additional, Cunningham, Christine, additional, Morley, Jessica, additional, Mehrkar, Amir, additional, Hart, Liam, additional, Davy, Simon, additional, Evans, David, additional, Hickman, George, additional, Inglesby, Peter, additional, Morton, Caroline E., additional, Smith, Rebecca M., additional, Ward, Tom, additional, O'Dwyer, Thomas, additional, Maude, Steven, additional, Bridges, Lucy, additional, Butler‐Cole, Ben F. C., additional, Stables, Catherine L., additional, Stokes, Pete, additional, Bates, Chris, additional, Cockburn, Jonny, additional, Hester, Frank, additional, Parry, John, additional, Bhaskaran, Krishnan, additional, Schultze, Anna, additional, Rentsch, Christopher T., additional, Mathur, Rohini, additional, Tomlinson, Laurie A., additional, Williamson, Elizabeth J., additional, Smeeth, Liam, additional, Walker, Alex, additional, Bacon, Sebastian, additional, MacKenna, Brian, additional, and Goldacre, Ben, additional

Published
2024
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33. Quantifying possible bias in clinical and epidemiological studies with quantitative bias analysis: common approaches and limitations

Author

Brown, Jeremy P, primary, Hunnicutt, Jacob N, additional, Ali, M Sanni, additional, Bhaskaran, Krishnan, additional, Cole, Ashley, additional, Langan, Sinead M, additional, Nitsch, Dorothea, additional, Rentsch, Christopher T, additional, Galwey, Nicholas W, additional, Wing, Kevin, additional, and Douglas, Ian J, additional

Published
2024
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36. Antiviral Strategies Against SARS-CoV-2: A Systems Biology Approach

Author

Prates, Erica T., primary, Garvin, Michael R., additional, Jones, Piet, additional, Miller, J. Izaak, additional, Sullivan, Kyle A., additional, Cliff, Ashley, additional, Gazolla, Joao Gabriel Felipe Machado, additional, Shah, Manesh B., additional, Walker, Angelica M., additional, Lane, Matthew, additional, Rentsch, Christopher T., additional, Justice, Amy, additional, Pavicic, Mirko, additional, Romero, Jonathon, additional, and Jacobson, Daniel, additional

Published
2022
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37. Baseline, Time-Updated, and Cumulative HIV Care Metrics for Predicting Acute Myocardial Infarction and All-Cause Mortality

Author

Salinas, Jorge L, Rentsch, Christopher, Marconi, Vincent C, Tate, Janet, Budoff, Matthew, Butt, Adeel A, Freiberg, Matthew S, Gibert, Cynthia L, Goetz, Matthew Bidwell, Leaf, David, Rodriguez-Barradas, Maria C, Justice, Amy C, and Rimland, David

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, HIV/AIDS, Prevention, Cardiovascular, Infectious Diseases, Clinical Research, Heart Disease - Coronary Heart Disease, Genetics, Good Health and Well Being, Adult, Aged, Aging, Biomarkers, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Myocardial Infarction, Predictive Value of Tests, Proportional Hazards Models, Risk Assessment, Risk Factors, United States, Veterans, Viremia, acute myocardial infarction, HIV, mortality, VACS Index, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

Background After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals.Methods We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death.Results A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11-5.20) for AMI and a HR of 31.77 (95% CI, 26.17-38.57) for mortality.Conclusions Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.

Published
2016

39. Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform

Author

Rentsch, Christopher T, DeVito, Nicholas J, MacKenna, Brian, Morton, Caroline E, Bhaskaran, Krishnan, Brown, Jeremy P, Schultze, Anna, Hulme, William J, Croker, Richard, Walker, Alex J, Williamson, Elizabeth J, Bates, Chris, Bacon, Seb, Mehrkar, Amir, Curtis, Helen J, Evans, David, Wing, Kevin, Inglesby, Peter, Mathur, Rohini, Drysdale, Henry, Wong, Angel Y S, McDonald, Helen I, Cockburn, Jonathan, Forbes, Harriet, Parry, John, Hester, Frank, Harper, Sam, Smeeth, Liam, Douglas, Ian J, Dixon, William G, Evans, Stephen J W, Tomlinson, Laurie, and Goldacre, Ben

Published
2021
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40. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform

Author

Bhaskaran, Krishnan, Rentsch, Christopher T, MacKenna, Brian, Schultze, Anna, Mehrkar, Amir, Bates, Chris J, Eggo, Rosalind M, Morton, Caroline E, Bacon, Sebastian C J, Inglesby, Peter, Douglas, Ian J, Walker, Alex J, McDonald, Helen I, Cockburn, Jonathan, Williamson, Elizabeth J, Evans, David, Forbes, Harriet J, Curtis, Helen J, Hulme, William J, Parry, John, Hester, Frank, Harper, Sam, Evans, Stephen J W, Smeeth, Liam, and Goldacre, Ben

Published
2021
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42. Sustained virological response after treatment with direct antiviral agents in individuals with HIV and hepatitis C co‐infection

Author

Lodi, Sara, Klein, Marina, Rauch, Andri, Epstein, Rachel, Wittkop, Linda, Logan, Roger, Rentsch, Christopher T., Justice, Amy C., Touloumi, Giota, Berenguer, Juan, Jarrin, Inma, Egger, Matthias, Puoti, Massimo, Monforte, Antonella D'Arminio, Gill, John, Ceron, Dominique Salmon, Sighem, Ard, Linas, Benjamin, Valk, Marc, and Hernán, Miguel A.

Subjects
HIV (Viruses) -- Drug therapy -- Patient outcomes, Antiviral agents -- Complications and side effects -- Patient outcomes, Hepatitis C virus -- Drug therapy -- Patient outcomes, Health
Abstract

: Introduction: Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct‐acting antiviral (DAA) treatment in individuals with HIV and HCV co‐infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non‐random samples of individuals with available post‐DAA HCV‐RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co‐infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV‐RNA testing. Methods: We included adults with HIV‐HCV co‐infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV‐RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g‐formula to impute SVR status for individuals with no SVR assessment. Results and Discussion: A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV‐RNA test on or after 12 weeks after the end of treatment. The overall observed and g‐formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post‐DAA and strategies for more systematic routine HCV‐RNA testing should be considered. Conclusions: Our estimates with and without adjustment for missing HCV‐RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials., INTRODUCTION Direct‐acting antiviral (DAA) treatment has revolutionized the treatment of hepatitis C virus (HCV) infection. The availability of DAAs is especially important for persons with HIV because HCV co‐infection, which [...]

Published
2022
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44. Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform

Author

Schultze, Anna, Walker, Alex J, MacKenna, Brian, Morton, Caroline E, Bhaskaran, Krishnan, Brown, Jeremy P, Rentsch, Christopher T, Williamson, Elizabeth, Drysdale, Henry, Croker, Richard, Bacon, Seb, Hulme, William, Bates, Chris, Curtis, Helen J, Mehrkar, Amir, Evans, David, Inglesby, Peter, Cockburn, Jonathan, McDonald, Helen I, Tomlinson, Laurie, Mathur, Rohini, Wing, Kevin, Wong, Angel Y S, Forbes, Harriet, Parry, John, Hester, Frank, Harper, Sam, Evans, Stephen J W, Quint, Jennifer, Smeeth, Liam, Douglas, Ian J, and Goldacre, Ben

Published
2020
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47. Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records

Author

Doran, William, primary, Tunnicliffe, Louis, additional, Muzambi, Rutendo, additional, Rentsch, Christopher T, additional, Bhaskaran, Krishnan, additional, Smeeth, Liam, additional, Brayne, Carol, additional, Williams, Dylan M, additional, Chaturvedi, Nish, additional, Eastwood, Sophie V, additional, Dunachie, Susanna J, additional, Mathur, Rohini, additional, and Warren-Gash, Charlotte, additional

Published
2024
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48. Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform

Author

Costello, Ruth E, primary, Waller, Karen MJ, additional, Smith, Rachel, additional, Mells, George F, additional, Wong, Angel YS, additional, Schultze, Anna, additional, Mahalingasivam, Viyaasan, additional, Herrett, Emily, additional, Zheng, Bang, additional, Lin, Liang-Yu, additional, Mehrkar, Amir, additional, Bacon, Sebastian CJ, additional, Goldacre, Ben, additional, Tomlinson, Laurie A, additional, Tazare, John, additional, and Rentsch, Christopher T., additional

Published
2023
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49. UK prevalence of underlying conditions which increase the risk of severe COVID-19 disease: a point prevalence study using electronic health records

Author

Walker, Jemma L., Grint, Daniel J., Strongman, Helen, Eggo, Rosalind M., Peppa, Maria, Minassian, Caroline, Mansfield, Kathryn E., Rentsch, Christopher T., Douglas, Ian J., Mathur, Rohini, Wong, Angel Y. S., Quint, Jennifer K., Andrews, Nick, Bernal, Jamie Lopez, Scott, J. Anthony, Ramsay, Mary, Smeeth, Liam, and McDonald, Helen I.

Published
2021
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50. Factors associated with COVID-19-related death using OpenSAFELY

Author

Williamson, Elizabeth J., Walker, Alex J., Bhaskaran, Krishnan, Bacon, Seb, Bates, Chris, Morton, Caroline E., Curtis, Helen J., Mehrkar, Amir, Evans, David, Inglesby, Peter, Cockburn, Jonathan, McDonald, Helen I., MacKenna, Brian, Tomlinson, Laurie, Douglas, Ian J., Rentsch, Christopher T., Mathur, Rohini, Wong, Angel Y. S., Grieve, Richard, Harrison, David, Forbes, Harriet, Schultze, Anna, Croker, Richard, Parry, John, Hester, Frank, Harper, Sam, Perera, Rafael, Evans, Stephen J. W., Smeeth, Liam, and Goldacre, Ben

Published
2020
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