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1. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice

Author: Peter von Dadelszen, Shigeru Saito, Louise C. Kenny, Sarosh Rana, Annemarie Hennessy, Mark Brown, Fergus McCarthy, Laura A. Magee, Sanjay Gupte, Jenny Myers, Anne Cathrine Staff, Eleni Tsigas, S. Ananth Karumanchi, Liona C. Poon, and David Hall
Subjects: Postnatal Care, medicine.medical_specialty, Pregnancy, business.industry, Obstetrics and Gynecology, Blood Pressure Determination, Audit, medicine.disease, Clinical trial, Proteinuria, Departmental management, Pre-Eclampsia, Risk Factors, Diagnosis management, Internal Medicine, medicine, Humans, Female, Intensive care medicine, business, Exercise, Antihypertensive Agents, Societies, Medical, reproductive and urinary physiology
Abstract: All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes. The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies.
Published: 2022
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2. <scp>WA</scp> Remote Aeromedical <scp>SUDs</scp> Outcomes

Author: Nicholas Faint, Mathew Coleman, Breeanna Spring, Alice Richardson, Ashleigh Thornton, Donna Bacon, Santharajah Kumaradevan, and Fergus W Gardiner
Subjects: Internal Medicine
Published: 2023
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3. Association Between Chronic Hypertension and the Risk of 12 Cardiovascular Diseases Among Parous Women: The Role of Adverse Pregnancy Outcomes

Author: Sukainah Al Khalaf, Lucy C. Chappell, Ali S. Khashan, Fergus P. McCarthy, and Éilis J. O’Reilly
Subjects: Internal Medicine
Abstract: BACKGROUND: Evidence on the association between chronic hypertension and the risk of cardiovascular disease (CVD) in mothers with adverse pregnancy outcomes (APOs) is limited. We investigated the association between chronic hypertension and risk of CVD, considering the role of APOs. METHODS: We used linked electronic health records in the CALIBER platform to define a UK cohort of women with recorded births between 1997 and 2016. We conducted multivariable Cox regression to estimate the association between chronic hypertension, with and without APOs, and 12 subsequent CVD events. RESULTS: The study cohort comprised 1 784 247 births (1.2 million women); of these 12 698 (0.71%) records had chronic hypertension, and 16 499 women had incident CVD during follow-up, of which 66% occurred in women under 40 years. Chronic hypertension (versus no chronic hypertension) was associated with a 2-fold higher risk of first subsequent CVD (adjusted hazard ratios, 2.22 [95% CI, 2.03–2.42]). Compared to normotensive women without APOs, the associations were the strongest in women with chronic hypertension and APOs across the 12 CVD outcomes, varying from 9.65 (5.96–15.6) for heart failure to 2.66 (2.17–3.26) for stable angina. In women with chronic hypertension without APOs, adjusted hazard ratios varied from 5.25 (3.47–7.94) for subarachnoid hemorrhage to 1.26 (0.59–2.67) for peripheral arterial disease. In women with APOs, but without chronic hypertension, adjusted hazard ratios varied from 3.27 (2.48–4.31) for intracerebral hemorrhage to 1.33 (1.26–1.41) for stable angina. CONCLUSIONS: We found strong associations between chronic hypertension and the risk of premature CVD, with greater risk in women who additionally had APOs. Intervention programs focused on these groups might lower their risk of subsequent CVD.
Published: 2023
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4. Psychological Health in Young Adults With Kidney Failure:A 5-Year Follow-up of the SPEAK Study

Author: Mohammed Al-Talib, Fergus J. Caskey, Carol Inward, Yoav Ben-Shlomo, and Alexander J. Hamilton
Subjects: Nephrology, Internal Medicine
Published: 2023
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5. Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort

Author: Paul Z, Benitez-Aguirre, M Loredana, Marcovecchio, Scott T, Chiesa, Maria E, Craig, Tien Y, Wong, Elizabeth A, Davis, Andrew, Cotterill, Jenny J, Couper, Fergus J, Cameron, Farid H, Mahmud, H Andrew W, Neil, Timothy W, Jones, Lauren A B, Hodgson, R Neil, Dalton, Sally M, Marshall, John, Deanfield, David B, Dunger, and Kim C, Donaghue
Subjects: Diabetes Mellitus, Type 1, Diabetic Retinopathy, Adolescent, Risk Factors, Albumins, Creatinine, Endocrinology, Diabetes and Metabolism, Internal Medicine, Albuminuria, Humans, Diabetic Nephropathies, Child
Abstract: Aims/hypothesis We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control. Methods This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as ‘high ACR’ or ‘low ACR’ (lowest and middle ACR tertiles) using baseline standardised log10 ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable. Results At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk. Conclusions/interpretation High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies. Trial registration isrctn.org ISRCTN91419926. Graphical abstract
Published: 2022
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6. Influence of Cancer Susceptibility Gene Mutations and ABO Blood Group of Pancreatic Cancer Probands on Concomitant Risk to First-Degree Relatives

Author: Kari G. Rabe, Samuel O. Antwi, Robert R. McWilliams, Sarah E Fagan, Shruti Chandra, Gloria M. Petersen, William R. Bamlet, Fergus J. Couch, Chunling Hu, Ann L. Oberg, and Margaret Meyer
Subjects: Male, Proband, medicine.medical_specialty, Epidemiology, Gastroenterology, Article, ABO Blood-Group System, Germline mutation, Risk Factors, Pancreatic cancer, ABO blood group system, Internal medicine, medicine, Humans, Family, Genetic Predisposition to Disease, Reference population, Registries, First-degree relatives, Aged, business.industry, Cancer Susceptibility Gene, Middle Aged, medicine.disease, Pancreatic Neoplasms, Oncology, Concomitant, Mutation, Female, business
Abstract: Background: ABO blood group is associated with pancreatic cancer risk. Whether ABO blood group alone or when combined with inherited mutation status of index pancreatic cancer cases (probands) can enhance pancreatic cancer risk estimation in first-degree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status. Methods: Data on 23,739 FDRs, identified through 3,268 pancreatic cancer probands, were analyzed. Probands' ABO blood groups were determined serologically or genetically, and 20 cancer susceptibility genes were used to classify probands as “mutation-positive” or “mutation-negative.” SIRs and 95% confidence intervals (CI) were calculated, comparing observed pancreatic cancer cases in the FDRs with the number expected in SEER-21 (reference population). Results: Overall, FDRs had 2-fold risk of pancreatic cancer (SIR = 2.00; 95% CI = 1.79–2.22). Pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.80; 95% CI = 2.81–5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57–2.04) probands (P < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIRblood-group-O = 1.57; 95% CI = 1.20–2.03, SIRnon-O = 1.83; 95% CI = 1.53–2.17; P = 0.33). Among FDRs of probands with non-O blood group, pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.98; 95% CI = 2.62–5.80) than mutation-negative (SIR = 1.66; 95% CI = 1.35–2.03) probands (P < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIRmutation-positive = 2.65; 95% CI = 1.09–5.47, SIRmutation-negative = 1.48; 95% CI = 1.06–5.47; P = 0.16). Conclusions: There is a range of pancreatic cancer risk to FDRs according to probands' germline mutation status and ABO blood group, ranging from 1.48 for FDRs of probands with blood group O and mutation-negative to 3.98 for FDRs of probands with non-O blood group and mutation-positive. Impact: Combined ABO blood group and germline mutation status of probands can inform pancreatic cancer risk estimation in FDRs.
Published: 2022
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7. National health policies and strategies for addressing chronic kidney disease: Data from the International Society of Nephrology Global Kidney Health Atlas

Author: Brendon L. Neuen, Aminu K. Bello, Adeera Levin, Meaghan Lunney, Mohamed A. Osman, Feng Ye, Gloria E. Ashuntantang, Ezequiel Bellorin-Font, Mohammed Benghanem Gharbi, Sara Davison, Mohammad Ghnaimat, Paul Harden, Vivekanand Jha, Kamyar Kalantar-Zadeh, Peter G. Kerr, Scott Klarenbach, Csaba P. Kovesdy, Valerie Luyckx, Shahrzad Ossareh, Jeffrey Perl, Harun Ur Rashid, Eric Rondeau, Emily J. See, Syed Saad, Laura Sola, Irma Tchokhonelidze, Vladimir Tesar, Kriang Tungsanga, Rumeyza Turan Kazancioglu, Angela Yee-Moon Wang, Chih-Wei Yang, Alexander Zemchenkov, Ming-hui Zhao, Kitty J. Jager, Fergus J. Caskey, Vlado Perkovic, Kailash K. Jindal, Ikechi G. Okpechi, Marcello Tonelli, John Feehally, David C. Harris, David W. Johnson, and KAZANCIOĞLU, RÜMEYZA
Subjects: Internal Diseases, Urology, Medicine (miscellaneous), Assessment and Diagnosis, Sağlık Bilimleri, Temel Bilgi ve Beceriler, Genel Tıp, Pathophysiology, İç Hastalıkları, Clinical Medicine (MED), TIP, GENEL & DAHİLİ, UROLOGY & NEPHROLOGY, Health Sciences, Internal Medicine, Klinik Tıp (MED), ÜROLOJİ VE NEFROLOJİ, Aile Sağlığı, MEDICINE, GENERAL & INTERNAL, Dahiliye, Patofizyoloji, Internal Medicine Sciences, Klinik Tıp, Fundamentals and Skills, Dahili Tıp Bilimleri, General Medicine, CLINICAL MEDICINE, Değerlendirme ve Teşhis, Tıp, Nefroloji, Nephrology, Üroloji, General Health Professions, Medicine, Tıp (çeşitli), Family Practice, Genel Sağlık Meslekleri
Abstract: National strategies for addressing chronic kidney disease (CKD) are crucial to improving kidney health. We sought to describe country-level variations in non-communicable disease (NCD) strategies and CKD-specific policies across different regions and income levels worldwide. The International Society of Nephrology Global Kidney Health Atlas (GKHA) was a multinational cross-sectional survey conducted between July and October 2018. Responses from key opinion leaders in each country regarding national NCD strategies, the presence and scope of CKD-specific policies, and government recognition of CKD as a health priority were described overall and according to region and income level. 160 countries participated in the GKHA survey, comprising 97.8% of the world’s population. Seventy-four (47%) countries had an established national NCD strategy, and 53 (34%) countries reported the existence of CKD-specific policies, with substantial variation across regions and income levels. Where CKD-specific policies existed, non-dialysis CKD care was variably addressed. 79 (51%) countries identified government recognition of CKD as a health priority. Low- and low-middle income countries were less likely to have strategies and policies for addressing CKD and have governments which recognise it as a health priority. The existence of CKD-specific policies, and a national NCD strategy more broadly, varied substantially across different regions around the world but was overall suboptimal, with major discrepancies between the burden of CKD in many countries and governmental recognition of CKD as a health priority. Greater recognition of CKD within national health policy is critical to improving kidney healthcare globally.
Published: 2023

8. Risk of Late-Onset Breast Cancer in Genetically Predisposed Women

Author: Lauren R. Teras, Siddhartha Yadav, Amy Trentham-Dietz, Dale P. Sandler, James M. Hodge, Elena Ma Martínez, Fergus J. Couch, Jack A. Taylor, Katie M. O'Brien, Alpa V. Patel, Christopher A. Haiman, Chunling Hu, Mia M. Gaudet, David E. Goldgar, Paul W. Auer, James V. Lacey, Nicholas J. Boddicker, Sara Lindström, Celine M. Vachon, Susan L. Neuhausen, Irene M. Ong, Kimberly A. Bertrand, Leslie Bernstein, Loic Le Marchand, Eric C. Polley, Janet E. Olson, Hongyan Huang, Christine B. Ambrosone, Tina Pesaran, Susan M. Domchek, Amal Yussuf, Nicole L. Larson, Rohan Gnanaolivu, Brian D. Carter, Song Yao, Steven N. Hart, Holly LaDuca, Rachid Karam, Jie Na, Chi Gao, Katherine L. Nathanson, Peter Kraft, Elizabeth C. Chao, Huiyan Ma, Jeffrey N. Weitzel, Julie R. Palmer, Christopher E. Scott, Charles Kooperberg, Jill S. Dolinsky, David J. Hunter, and Elizabeth S. Burnside
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Population, MEDLINE, Breast Neoplasms, Late onset, Germline, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, RAPID COMMUNICATIONS, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Age of Onset, skin and connective tissue diseases, education, Germ-Line Mutation, Aged, Aged, 80 and over, BRCA2 Protein, education.field_of_study, BRCA1 Protein, business.industry, Prognosis, medicine.disease, Checkpoint Kinase 2, Germ Cells, 030104 developmental biology, Case-Control Studies, 030220 oncology & carcinogenesis, cardiovascular system, Female, Fanconi Anemia Complementation Group N Protein, business, Follow-Up Studies
Abstract: PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)–negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.
Published: 2021
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9. The state of the global nephrology workforce: a joint ASN–ERA-EDTA–ISN investigation

Author: Fergus Caskey, Adeera Levin, Kurtis A. Pivert, and Stephen M. Sozio
Subjects: Nephrology, medicine.medical_specialty, business.industry, kidney disease, medicine.medical_treatment, nephrology, global health, medicine.disease, Internal medicine, Family medicine, Workforce, medicine, Global health, physician workforce, dialysis, Physician workforce, nephrologist, business, Dialysis, Kidney disease
Published: 2021
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10. Management of Colorectal Cancer with Synchronous Liver Metastases: An Inception Cohort Study (CoSMIC)

Author: Jonathan I. Epstein, Saifee Mullamitha, Fergus Reid, Aali J. Sheen, Michael Braun, Mohammud Kurrimboccus, Jurjees Hassan, Kamran Siddiqui, Thomas Satyadas, Arif Khan, Santhalingam Jegatheeswaran, James Mason, Derek A. O'Reilly, Raj Rajashankar, Rahul Deshpand, Rishi Sethi, Minas Baltatzis, Anthony K.C. Chan, Raymond Mcmahon, Saurabh Jamdar, Nicola de Liguori Carino, James O. Hill, Marius Paraoan, Gregory C. Wilson, Christopher Smart, Ajith K. Siriwardena, Nooreen Alam, David J. Smith, and Ramesh Aswatha
Subjects: medicine.medical_specialty, Chemotherapy, Colorectal cancer, business.industry, medicine.medical_treatment, Cancer, Perioperative, medicine.disease, INCEPTION COHORT, Oncology, Quality of life, Surgical oncology, Internal medicine, medicine, Surgery, business, Body mass index
Abstract: BACKGROUND Approximately one-fifth of patients with colorectal cancer present with hepatic metastases. There are limited prospective data on the outcomes of synchronous combined liver and bowel surgery and liver-first or bowel-first routes where contemporary chemo(radio)therapy is integrated into management. METHODS Between 1 April 2014 and 31 March 2017, 125 patients with colorectal cancer and synchronous liver metastases were recruited. Data are reported on pathway-specific outcomes, including perioperative complications, treatment completion, and overall and disease-free survival. The study was registered with ClinicalTrials.gov (NCT02456285). RESULTS There was no difference in age, body mass index, or Charlson score between surgical groups. Neoadjuvant chemotherapy was used in 50 (40%) patients for a mean duration of 4.6 months (standard deviation [SD] 5.4), and mean time from completion of chemotherapy to surgery was 2.6 months (SD 1.9). Complications were similar between patients completing the synchronous and staged pathways (p = 0.66). Mean total inpatient stay was 16.5 days (SD 8.1) for staged surgery compared with 16.8 days (SD 10.3) for the synchronous group (t-test; p = 0.91). There was no difference in time to treatment completion between pathways. Thirty six (35%) patients were disease-free at 12 months, with no significant difference between groups (Chi-square, p = 0.448). Quality of life was similar in all surgical groups. CONCLUSIONS Perioperative complications and oncological and healthcare occupancy outcomes are equivalent between patients completing staged and synchronous pathways for the management of patients with colorectal cancer and synchronous liver metastases. Future studies should focus on optimizing the criteria for pathway selection, incorporation of cancer genomics data, and patient (user) preferences.
Published: 2021
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11. Prognostic factors in triple-negative breast cancer: a retrospective cohort

Author: Fergus Tomás Rocha de Oliveira, Ana Lúcia Nascimento Araújo, Sabas Carlos Vieira, and Rafael Everton Assunção Ribeiro da Costa
Subjects: Oncology, medicine.medical_specialty, Medicine (General), medicine.medical_treatment, Sentinel lymph node, Pathological conditions, Triple Negative Breast Neoplasms, Cohort Studies, Breast cancer, R5-920, Internal medicine, Risk of mortality, medicine, Humans, Survival analysis, Triple-negative breast cancer, Mastectomy, Retrospective Studies, Medical records, Triple-negative breast neoplasms, business.industry, Anatomical, Retrospective cohort study, General Medicine, medicine.disease, Prognosis, Female, business, Cohort study
Abstract: SUMMARY OBJECTIVE: Triple-negative breast cancer (TNBC) is characterized by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression and accounts for 15–20% of all breast cancers. This study aims to analyze prognostic factors related to a reduction in overall survival (OS), disease-free survival (DFS), and risk of mortality and recurrence in TNBC. METHODS: This is a retrospective observational cohort study. Medical records of 532 patients with breast cancer diagnosed from 2007 to 2020 were analyzed. Of these patients, 93 (17%) were women with TNBC. Ten medical records were excluded, and the final sample was composed of 83 women with TNBC. OS and DFS were estimated by the Kaplan-Meier model. Univariate analysis (log-rank test) and multivariate analysis (Cox regression) were used to examine prognostic factors related to a statistically significant reduction (p
Published: 2021

12. The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Author: Lakeman, Inge M. M., Van Den Broek, Alexandra J., Vos, Juliën A. M., Barnes, Daniel R., Adlard, Julian, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Balmaña, Judith, Barrowdale, Daniel, Giraud, Sophie, Golmard, Lisa, Hake, Christopher R., Houdayer, Claude, Risch, Harvey A., Lasset, Christine, Laurent, Maïté, Spurdle, Amanda B., Hooning, Maartje J., Hopper, John L., Kets, Carolien M., Leroux, Dominique, Longy, Michel, Mari, Véronique, Mazoyer, Sylvie, Mebirouk, Noura, Mortemousque, Isabelle, Blok, Marinus J., Prieur, Fabienne, Hamann, Ute, Pujol, Pascal, Konstantopoulou, Irene, Heemskerk Gerritsen, Bernadette A. M., Isaacs, Claudine, Saule, Claire, Piedmonte, Marion, Schuster, Helene, Sevenet, Nicolas, Sobol, Hagay, Sokolowska, Johanna, Gómez Garcia, Encarna B., Venat Bouvet, Laurence, Claes, Kathleen B. M., Ahmed, Munaza, Teixeira, Manuel R., Barwell, Julian, Brady, Angela, Izatt, Louise, Hogervorst, Frans B. L., Brennan, Paul, Harrington, Patricia A., Henderson, Alex, Hodgson, Shirley, Kwong, Ava, Borg, Ake, Kennedy, M. John, Porteous, Mary E., Rogers, Mark T., Side, Lucy E., Snape, Katie, Walker, Lisa, Collée, J. Margriet, Jakubowska, Anna, Couch, Fergus J., Hahnen, Eric, Daly, Mary B., Dennis, Joe, Teo, Soo Hwang, Jensen, Uffe Birk, Rantala, Johanna, Dhawan, Mallika, Benitez, Javier, Domchek, Susan M., Eeles, Ros, Engel, Christoph, Legrand, Clémentine, Evans, D. Gareth, James, Paul A., Feliubadaló i Elorza, Maria Lídia, Teulé-Vega, Àlex, Foretova, Lenka, Castera, Laurent, Friedman, Eitan, Frost, Debra, Rennert, Gad, Ganz, Patricia A., Leslie, Goska, Garber, Judy, Hulick, Peter J., Imyanitov, Evgeny N., Glendon, Gord, Thomassen, Mads, Janavicius, Ramunas, Mulligan, Anna Marie, Hollestelle, Antoinette, Jager, Agnes, Koppert, Linetta B., Cook, Jackie, Koudijs, Marco, Kriege, Mieke, Meijers Heijboer, Hanne E. J., Schmutzler, Rita K., Mensenkamp, Arjen R., Dunning, Alison M., Mooij, Thea M., Oosterwijk, Jan C., Caux Moncoutier, Virginie, Singer, Christian F., Berthet, Pascaline, Caldés, Trinidad, Van den Ouweland, Ans M. W., Van der Baan, Frederieke H., Van der Hout, Annemieke H., Van der Kolk, Lizet E., Van der Luijt, Rob B., Thull, Darcy L., Van Deurzen, Carolien H. M., Sharma, Priyanka, Van Doorn, Helena C., Bignon, Yves Jean, Colas, Chrystelle, Van Engelen, Klaartje, Brewer, Carole, Van Hest, Liselotte P., Van Os, Theo A. M., Caligo, Maria A., Verhoef, Senno, Tischkowitz, Marc, Vogel, Maartje J., Wijnen, Juul T., Lalloo, Fiona, Beesley, Jonathan, Fox, Stephen, Collonge Rame, Marie Agnès, Simard, Jacques, Holland, Helene, Jiao, Yue, John, Esther M., Joseph, Vijai, Gerdes, Anne Marie, Karlan, Beth Y., Lesueur, Fabienne, Loud, Jennifer T., Lubiński, Jan, Manoukian, Siranoush, Mcguffog, Lesley, Miller, Austin, Coupier, Isabelle, Gomes, Denise Molina, Barouk Simonet, Emmanuelle, Montagna, Marco, Miller, Clare, Elan, Camille, Davidson, Rosemarie, Mouret Fourme, Emmanuelle, Gayther, Simon A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Pauw, Antoine de, Olah, Edith, Morrison, Patrick J., Olopade, Olufunmilayo I., Van Asperen, Christi J., Park, Sue K., Parsons, Michael T., Donaldson, Alan, Belotti, Muriel, Peterlongo, Paolo, Stadler, Zsofia, Stoppa Lyonnet, Dominique, Sutter, Christian, Ong, Kai Ren, Delnatte, Capucine, Tan, Yen Yen, Toland, Amanda E., Tung, Nadine, Van Rensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Devilee, Peter, Eason, Jacqueline, Chung, Wendy K., Bernstein, Jonine L., Offit, Kenneth, Aalfs, Cora M., Hanson, Helen, Godwin, Andrew K., Easton, Douglas F., Bonadona, Valérie, Rookus, Matti A., Chenevix-Trench, Georgia, Antoniou, Antonis C., O’shaughnessy Kirwan, Aoife, Robson, Mark, Eccles, Diana M., Schmidt, Marjanka K., Adank, Muriel A., Gemo Study Collaborators, Phillips, Kelly Anne, Embrace Collaborators, Ocgn Investigators, Goldgar, David E., Hebon Investigators, Perkins, Jo, Kconfab Investigators, Bressac de Paillerets, Brigitte, Buecher, Bruno, Caputo, Sandrine, Ausems, Margreet G. E. M., Gregory, Helen, Caron, Olivier, Faivre, Laurence, Fert Ferrer, Sandra, Gauthier Villars, Marion, Radice, Paolo, Gesta, Paul, Clinical Genetics, Medical Oncology, Surgery, Pathology, Gynecological Oncology, Schmidt, Marjanka K. [0000-0002-2228-429X], Apollo - University of Cambridge Repository, Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Schmidt, Marjanka K [0000-0002-2228-429X], HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Institut Català de la Salut, [Lakeman IMM] Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. [van den Broek AJ, Vos JAM] Division of Molecular Pathology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. [Barnes DR] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Adlard J] Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK. [Andrulis IL] Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. [Balmaña J] Hereditary cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Pediatric surgery, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Cancer biology and immunology, Epidemiology and Data Science, Human Genetics, ARD - Amsterdam Reproduction and Development, APH - Personalized Medicine, APH - Quality of Care, Chapel Allerton Hospital, University of Leeds, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Reykjavík University, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, The University of Texas M.D. Anderson Cancer Center [Houston], Unitat d'Alt Risc i Prevenció del Càncer, Vall d'Hebron University Hospital [Barcelona], University of Cambridge [UK] (CAM), Group of Human Genetics, Human Cancer Genetics Programme, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Section of Genetic Oncology, University of Pisa - Università di Pisa, Columbia University [New York], Ghent University Hospital, Department of Clinical Genetics, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Laboratory Medicine and Pathology, Mayo Clinic, Division of Population Science, Fox Chase Cancer Center, Institut Curie [Paris], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL), CHU Grenoble, CHI Poissy-Saint-Germain, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA KG Polikliniek (9), and Klinische Genetica
Subjects: 0301 basic medicine, Percentile, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [DISEASES], Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], SUSCEPTIBILITY ALLELES, Diàtesi, FAMILIES, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], MESH: BRCA2 Protein, Breast cancer, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Other subheadings::/diagnosis [Other subheadings], Medicine and Health Sciences, Medicine, Mama - Càncer - Diagnòstic, Family history, skin and connective tissue diseases, Genetics (clinical), MESH: Heterozygote, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Factors de risc en les malalties, BRCA1 Protein, Hazard ratio, MESH: Genetic Predisposition to Disease, 1184 Genetics, developmental biology, physiology, article, OVARIAN, BRCA2 Protein/genetics, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, 030220 oncology & carcinogenesis, Female, Malalties congènites, Adult, Heterozygote, medicine.medical_specialty, MESH: Mutation, Risk factors in diseases, Otros calificadores::/diagnóstico [Otros calificadores], Breast Neoplasms, Context (language use), MUTATION CARRIERS, Càncer de mama, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::susceptibilidad a enfermedades::predisposición genética a la enfermedad [ENFERMEDADES], 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Humans, Genetic Predisposition to Disease, MESH: BRCA1 Protein, Retrospective Studies, BRCA2 Protein, MESH: Humans, business.industry, Proportional hazards model, CONSORTIUM, Breast Neoplasms/diagnosis, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, Confidence interval, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, BRCA1 Protein/genetics, 3111 Biomedicine, business, MESH: Female, MESH: Breast Neoplasms
Abstract: Predicció de risc de càncer de mama; Dones europees; Variant patògena heterozigota Predicción del riesgo de cáncer de mama; Mujeres europeas; Variante patógena heterocigota Breast cancer risk prediction; European women; Heterozygous pathogenic variant Purpose To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC
Published: 2021
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13. Adolescent ambivalence about diabetes technology-The Janus faces of automated care

Author: Fergus J. Cameron, Michael Arnold, and John W. Gregory
Subjects: Technology, Adolescent, Endocrinology, Diabetes and Metabolism, Pediatrics, Perinatology and Child Health, Internal Medicine, Diabetes Mellitus, Humans, Prospective Studies, Retrospective Studies
Abstract: The Janus face metaphor approach highlights that a technology may simultaneously have two opposite faces or properties with unforeseen paradoxes within human-technology interaction. Suboptimal acceptance and clinical outcomes are sometimes seen in adolescents who use diabetes-related technologies. A traditional linear techno-determinist model of technology use would ascribe these unintended outcomes to suboptimal technology, suboptimal patient behavior, or suboptimal outcome measures. This paradigm has demonstratively not been successful at universally improving clinical outcomes over the last two decades. Alternatively, the Janus face metaphor moves away from a linear techno-determinist model and focuses on the dynamic interaction of the human condition and technology. Specifically, it can be used to understand variance in adoption or successful use of diabetes-related technology and to retrospectively understand suboptimal outcomes. The Janus face metaphor also allows for a prospective exploration of potential impacts of diabetes-related technology by patients, families, and their doctors so as to anticipate and minimize potential subsequent tensions.
Published: 2022

14. Increasing evidence of the benefits of a transition coordinator in type 1 diabetes

Author: Michele A O'Connell, Katharine Steinbeck, Mary White, Raghu Lingam, and Fergus J. Cameron
Subjects: Type 1 diabetes, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, law.invention, Randomized controlled trial, law, Intervention (counseling), Internal Medicine, medicine, Physical therapy, business
Published: 2021
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15. Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score

Author: Amy Trentham-Dietz, Katie M. O'Brien, Alpa V. Patel, Rohan Gnanaolivu, Chi Gao, Katherine L. Nathanson, Lauren R. Teras, Clarice R. Weinberg, Nicholas J. Boddicker, David J. Hunter, Julie R. Palmer, Polly A. Newcomb, Jeffrey N. Weitzel, Eric J. Jacobs, Dale P. Sandler, Jenna Lilyquist, Leslie Bernstein, Rulla M. Tamimi, Christine B. Ambrosone, Fergus J. Couch, Celine M. Vachon, Esther M. John, Christopher A. Haiman, Jack A. Taylor, Hongyan Huang, Mia M. Gaudet, David E. Goldgar, Irene M. Ong, Susan M. Domchek, Chunling Hu, Sara Lindström, Jie Na, Elizabeth S. Burnside, Susan L. Neuhausen, Janet E. Olson, Eric C. Polley, Song Yao, Peter Kraft, Huiyan Ma, Steven N. Hart, A. Heather Eliassen, and Paul L. Auer
Subjects: Adult, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, MEDLINE, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Gene, Aged, business.industry, Genetic Variation, ORIGINAL REPORTS, Middle Aged, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Polygenic risk score, business
Abstract: PURPOSE This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. METHODS A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor–specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC. RESULTS The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of BRCA1, BRCA2, and PALB2 carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of ATM and CHEK2 carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk. CONCLUSION PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of CHEK2 and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.
Published: 2021
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16. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis

Author: Agata Majewska, Jessica A Marathe, Jenny Chambers, Romana Brun-Furrer, Ugo Indraccolo, Yue Cui, Stefan C. Kane, George Attilakos, Maria C. Estiú, L.F. Audris Wong, Andrew Shennan, Rachel M. Tribe, Michael J. Peek, Richard H. Lee, Keren Zloto, Jim G Thornton, Hanns-Ulrich Marschall, Tharni Vasavan, Yoav Yinon, Yannick Bacq, Caroline Ovadia, Berrin Günaydin, Xiaohua Liu, Yayi Hu, Catherine Williamson, Jūratė Kondrackienė, Ayse Gul Kebapcilar, Martijn A. Oudijk, Qianwen Zhang, Kasia Maksym, Victoria Geenes, William M. Hague, Alexander Juusela, Min Ding, Levent Kebapcilar, Valeria Tripodi, Deniz Oztekin, Kajol Patel, Rocio I.R. Macias, Nicholas A. Williamson, Christian Haslinger, Monika Grymowicz, Linoy Batsry, Fergus W. Gardiner, Naciye Turk Ozterlemez, Riza Madazli, Lucy C Chappell, Peter H. Dixon, Paul T. Seed, Anna Locatelli, Kelsey Broom, Maria P.H. Koster, Laura N. Bull, Jenna Sajous, Adam Morton, Francesco Azzaroli, Katherine Kohari, Ovadia C., Sajous J., Seed P.T., Patel K., Williamson N.J., Attilakos G., Azzaroli F., Bacq Y., Batsry L., Broom K., Brun-Furrer R., Bull L., Chambers J., Cui Y., Ding M., Dixon P.H., Estiu M.C., Gardiner F.W., Geenes V., Grymowicz M., Gunaydin B., Hague W.M., Haslinger C., Hu Y., Indraccolo U., Juusela A., Kane S.C., Kebapcilar A., Kebapcilar L., Kohari K., Kondrackiene J., Koster M.P.H., Lee R.H., Liu X., Locatelli A., Macias R.I.R., Madazli R., Majewska A., Maksym K., Marathe J.A., Morton A., Oudijk M.A., Oztekin D., Peek M.J., Shennan A.H., Tribe R.M., Tripodi V., Turk Ozterlemez N., Vasavan T., Wong L.F.A., Yinon Y., Zhang Q., Zloto K., Marschall H.-U., Thornton J., Chappell L.C., Williamson C., Obstetrics and Gynaecology, ARD - Amsterdam Reproduction and Development, Ovadia, C, Sajous, J, Seed, P, Patel, K, Williamson, N, Attilakos, G, Azzaroli, F, Bacq, Y, Batsry, L, Broom, K, Brun-Furrer, R, Bull, L, Chambers, J, Cui, Y, Ding, M, Dixon, P, Estiu, M, Gardiner, F, Geenes, V, Grymowicz, M, Gunaydin, B, Hague, W, Haslinger, C, Hu, Y, Indraccolo, U, Juusela, A, Kane, S, Kebapcilar, A, Kebapcilar, L, Kohari, K, Kondrackiene, J, Koster, M, Lee, R, Liu, X, Locatelli, A, Macias, R, Madazli, R, Majewska, A, Maksym, K, Marathe, J, Morton, A, Oudijk, M, Oztekin, D, Peek, M, Shennan, A, Tribe, R, Tripodi, V, Turk Ozterlemez, N, Vasavan, T, Wong, L, Yinon, Y, Zhang, Q, Zloto, K, Marschall, H, Thornton, J, Chappell, L, Williamson, C, Obstetrics & Gynecology, and Amsterdam Reproduction & Development (AR&D)
Subjects: Cholagogues and Choleretics, medicine.medical_specialty, medicine.drug_class, Cholestasis, Intrahepatic, 03 medical and health sciences, 0302 clinical medicine, Cholestasis, Pregnancy, Internal medicine, Cholestasis of pregnancy, Humans, Medicine, Hepatology, Bile acid, business.industry, Obstetrics, Individual participant data, Gastroenterology, Obstetrics and Gynecology, General Medicine, Odds ratio, medicine.disease, Ursodeoxycholic acid, Pregnancy Complications, 030220 oncology & carcinogenesis, Meta-analysis, Female, 030211 gastroenterology & hepatology, stillbirth, Ursodeoxycholic acid, pregnancy, intrahepatic cholestasis of pregnancy, business, medicine.drug, Cohort study
Abstract: Background: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35–3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04–2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86–1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39–0·91; p=0·016). Interpretation: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Funding: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.
Published: 2021

17. Use of Flecainide in Stable Coronary Artery Disease: An Analysis of Its Safety in Both Nonobstructive and Obstructive Coronary Artery Disease

Author: Nway L. Ko Ko, Sai Harika Pujari, Vatsal Ladia, Pradyumna Agasthi, Hasan Ashraf, Luis R. Scott, Dan Sorajja, Fergus O’Herlihy, Tadhg Prendiville, and Siva K. Mulpuru
Subjects: medicine.medical_specialty, Stress testing, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, Myocardial perfusion imaging, 0302 clinical medicine, Internal medicine, medicine, Humans, Pharmacology (medical), cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Flecainide, Retrospective Studies, Proarrhythmia, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, medicine.anatomical_structure, Cardiology, Cardiology and Cardiovascular Medicine, business, Perfusion, medicine.drug, Artery
Abstract: Flecainide is a class IC antiarrhythmic drug that is contraindicated in patients who have a history of myocardial infarction, but its effect on mortality and risk of proarrhythmia in patients with stable obstructive and nonobstructive epicardial coronary artery disease (CAD) has not been assessed. We sought to compare the safety of flecainide administration in patients who had angiographic evidence of either no or minimal CAD versus nonobstructive CAD, and those who underwent nuclear stress testing with perfusion defects versus those without perfusion defects. We conducted a retrospective chart review of 348 patients who were treated with flecainide for at least 1 year duration and underwent evaluation for CAD with coronary angiography or myocardial perfusion imaging (MPI) stress testing within 3 months of initiating flecainide. We compared overall mortality and proarrhythmia between varying levels of CAD and perfusion defects. There was a similar 10-year survival between those with no or minimal CAD, nonobstructive CAD, and obstructive CAD (p = 0.6). Additionally, there was no difference in arrhythmia burden, including sustained ventricular tachycardias or frequent premature ventricular contractions (> 5% daily burden; p = 0.25). There was also no increase in mortality among those who had reversible perfusion defects >0% compared with those without, among subjects who underwent MPI (p = 0.14). On subgroup analysis, there was no increased risk in all-cause mortality with any specific coronary artery involvement, or with obstructive multivessel CAD (p = 0.89). Flecainide use is not associated with an increase in either all-cause mortality or ventricular arrhythmias in low-risk patients with stable nonobstructive CAD.
Published: 2021
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18. Exercise oscillatory ventilation during autonomic blockade in young athletes and healthy controls

Author: Kris Nilsen, Fergus Sully, D. Flannery, Andrew T. Jeklin, Matthew T. Naughton, Andre La Gerche, Vaughan G. Macefield, and Matthew J Ellis
Subjects: medicine.medical_specialty, Sports medicine, Physiology, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, Autonomic blockade, medicine, Orthopedics and Sports Medicine, Tidal volume, Metoprolol, biology, Athletes, business.industry, Public Health, Environmental and Occupational Health, 030229 sport sciences, General Medicine, biology.organism_classification, medicine.disease, Atropine, Heart failure, Periodic breathing, Cardiology, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Exercise oscillatory ventilation (EOV) is a form of periodic breathing that is associated with a poor prognosis in heart failure patients, but little is known about EOV in other populations. We sought to provide insights into the phenomenon of EOV after it was observed in young healthy subjects, including athletes, after the administration of dual autonomic blockade (DAB). From 29 participants who completed cardiopulmonary exercise testing (CPET) with and without DAB (0.04 mg/kg atropine and 0.2 mg/kg metoprolol), 5 subjects developed EOV (age = 29 ± 5 years; 3/5 were athletes) according to American Heart Association criteria. For each case, we identified 2 non-EOV healthy controls (age = 34.2 ± 8.3; 7/10 were athletes) that were subsequently age- and sex-matched. No participants had EOV during exercise without DAB. The 5 participants (4 male, 1 female) who demonstrated EOV with DAB had lower mean tidal volume (1.7 ± 0.5 L/min vs. 1.8 ± 0.5 L/min; p = 0.04) compared to participants in the non-EOV group and a decrease in peak tidal volume (2.9 ± 0.6 L/min to 2.2 ± 0.7 L/min; p = 0.004) with DAB. There were few other differences in CPET measures between EOV and non-EOV participants, although the PETCO2 tended to be higher in the EOV group (p = 0.07). EOV can be elucidated in young healthy subjects, including athletes, during cardiopulmonary exercise testing, suggesting that it may not be an ominous sign in all populations.
Published: 2021
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19. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Nabeel Abdallah, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, David Abdo, Basir Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Amina Abdulle, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Ul Amna Abeer Ul Amna, Katrina Abernethy, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Sarah Acheampong, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Sara Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Charlotte Adams, Kate Adams, Lisa Adams, Richard Adams, Tim Adams, Kirsty Adcock, Jemaimah Addai, Ade Adebiyi, Ken Adegoke, Vicki Adell, Debo Ademokun, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Rina Adhikary, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Debbie Affleck, Dominic Affron, Carmel Afnan, Muhammad Afridi, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Penny Agent, Sunil Aggarwal, Arameh Aghababaie, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Humayun Ahmad, Mohammad Ahmad, Syed Ahmad, Asim Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Iram Ahmed, Irshad Ahmed, Khaled Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Sophia Ahmed, Syed Ahmed, Syed Haris Ahmed, Roa Ahmed Ali, Sana Ahmed, Sana Ahmer, Dhiraj Ail, Mark Ainsworth, Giulia Airoldi, Myriam Aissa, Lindianne Aitken, Bini Ajay, Francis Ajeneye, Abdulakeem Ajibode, Ayesha Ajmi, Tahir Akbar, Naim Akhtar, Nasim Akhtar, Nauman Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Olajide Akinwumiju, Olugbenro Aktinade, Ahmad Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Narendra Aladangady, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Karina Al-Asadi, Kyriaki Alatzoglou, Manaf Al-Bayati, Paul Albert, Lorraine Albon, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter D G Alexander, Charlotte Alford, Julyan Al-Fori, Laith Alghazawi, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Asad Ali, Fawzia R Ali, Hoodo Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Nayab Ali, Oudai Ali, Sabira Ali, Sakina Ali, Syed Ali, Abid Alina, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Moutaz Alkhusheh, Allameddine Allameddine, Fiona Allan, Rachel Allan, Alison Allanson, Robert Allcock, Beverley Allen, Eireann Allen, Jess Allen, Kerry Allen, Laura Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Sara Altaf, Mary Alvarez, Balaal Alyas, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Kenneth Amenyah, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Amjad Amjad, Neelma Amjad, Mariam Ammoun, Victoria Amosun, Khaled Amsha, Pugh Amy, Atul Anand, Rekha Anand, Samantha Anandappa, Julie Anderson, Kevin Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Susan Andrews, Gregory Andrikopoulos, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, George Apostolides, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia Far Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Emily Arbon, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Sylvia Armstrong-Fisher, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Sarah Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Andrea Arroyo, Arslam Arter, Ayush Arya, Rita Arya, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Glen Ashby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Deborah Asher, 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Dinh, Tri Dinh, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Caroline Dixon, Giles Dixon, Stephen Dixon-Mould, Brice Djeugam, Petr Dlouhy, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Joanne Donnachie, Christopher Donnelly, Eilish Donnelly, Ronan Donnelly, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Sinead Donton, Emma Dooks, Grainne Doran, Kane Dorey, Sharon Dorgan, Amanda Dornan, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Katie Douglas, Jonathan Douse, Lucy Dowden, Michelle Dower, Kerry Dowling, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Philippa 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Eagles, Joanne Early, Melissa Earwaker, Nicholas Easom, Clare East, Kim East, Amy Easthope, Fraser Easton, Caroline Eaton, Caroline Eaton-Howell, Ruth Eatough, Adrian Ebbs, Oluwadamilola Ebigbola, Daniel Ebner, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Julie Edmonds, Dave Edmondson, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Tomos Edwards, Jenny Eedle, Dawn Egginton, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Moulod El-Agnaf, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Diana Eleanor, Ibrahim Eletu, Eman Elfar, Mayy Magdy Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Mohammed El-Karim, Andrew Victor Elkins, Julie Ellam, Nikki Ellard, Laura Nicola Ellerton, Lucy Elliot, Amy Elliott, Chris Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Toby Elliott, Annie Ellis, Ann-Marie Ellis, Christine Ellis, Kay Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Megan Ellison, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed Elmi, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Robert Elshaw, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Helen Escreet, Peter Eskander, Hanif Esmail, Lise Estcourt, Amy Evans, Brynach Evans, Chris Evans, Daren Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Lisa Evans, Lynn Evans, Margaret Evans, Michelle Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Ryan Evans, Teriann Evans, Terry John Evans, Tony Eve, Caroline Everden, Serenydd Everden, Hayley Evison, Lynsey Evison, Penny Eyton-Jones, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, Jonathan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Qayyum Farah, Novin Fard, Amr Farg, Margaret Farinto, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Karen Farrar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Maria Faulkner, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Kelly Feane, Simon Fearby, Alex Feben, Federico Fedel, Daria Fedorova, James Feely-Henderson, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Stephanie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Callum Jeevan Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari Gersogamo, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Len Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Sarah Finbow, Debbie Finch, Joanne Finch, Laurie Finch, Joanne Finden, Natalie Fineman, Lauren Finlayson, Adam Finn, Joanne Finn, Clare Finney, Sofia Fiouni, Jo Fiquet, Dani Fisher, Emily Fisher, James Fisher, Neil Fisher, Meadow Fisher Crisp, Daniel Fishman, Krystofer Fishwick, Lorraine Fitzgerald, Chloe Fitzpatrick-Creamer, Jan Flaherty, Michael Flanagan, Charles Flanders, Cathy Flatters, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Karen Flewitt, Christopher Flood, Ian Floodgate, Vincent Florence, Sharon Floyd, Kelly Flynn, Rachel Flynn, Sara Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Claire Foley, Paul Foley, Linda Folkes, Daniela Mock Font, Evodian Fonyonga, Aiwyne Foo, Jane Foo, Andrew Foot, Jayne Foot, Jane Forbes, Jamie Ford, Kathy Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Theodora Foukanelli, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Daniel Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Yasin Fozdar, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Jason Frankcam, Helen Frankland, Gayle Franklin, Jessica Franklin, Darron Franks, Catherine Fraser, Laura Fraser, Sharon Frayling, Martyn Fredlund, Matthew Free, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Ian Freestone, Eleanor French, Matthew Frise, Renate Fromson, Claire Froneman, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Jake Fryer, Janet Fu, Bridget Fuller, Liz Fuller, Neil Fuller, Tracy Fuller, Duncan Fullerton, Jenny Fullthorpe, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Charlene Furtado, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Diana Gabriel, Hadiza Gachi, Rose Gad, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Zacharoula Galani, Christopher Gale, Hugo Gale, Rebecca Gale, Swetha Gali, Karen Galilee, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Laura Gamble, Liz Gamble, Brian Gammon, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Abrar Gani, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Jill Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Justin Garner, Lucie Garner, Zoe Garner, Kimberley Garnett, Robert Garney, Rosaline Garr, Michael Garstka, Peter Gartan, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Noha Gasmalseed, Michaela Gaspar, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Alison Geddis, Ian Gedge, Sarah Gee, Minerva Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Susan Gent, Natalie Geoghegan, Chloe George, Sam George, Tina George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Hisham Ghanayem, Amardeep Ghattaoraya, Anca Gherman, Alison Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Andrew Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Cat Gilbert, Jeanette Gilbert, Joanne Gilbert, Kayleigh Gilbert, Sean Gilchrist, Benjamin Giles, Mandy Gill, Rose Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Matt Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Theodora Giokanini-Royal, Anna Gipson, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Ana Glennon, John Glover, Kyle Glover, Jan Glover Bengtsson, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Gillian Godding, Emma Godson, Gerry Gogarty, Sukanya Gogoi, Aiky Goh, Rebeca Goiriz, Sriya Gokaraju, Philip Gold, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Bob Goodenough, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Sharif Goolam-Hossen, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Peter Gordon, Sally Gordon, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Diana Gorog, Jan Gorry, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Amanda Gould, Angela Gould, Susan Gould, Lysander Gourbault, Anna Gouveia, Abha Govind, Sharon Gowans, Girish Gowda, Rohit Gowda, Pauline Gowdy, Hannah Gower, Thomas Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Beverley Graham, Clive Graham, Jane Graham, Jonathan Graham, Justin Graham, Libby Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, 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Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Stephen Grist, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Sharazeq Guettari, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Malin Gunawardena, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Rishi Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Victoria Guratsky, Alvyda Gureviciute, Sambasivarao Gurram, Bhawana Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Berkin Hack, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Nikolaos Hadjisavvas, Leah Hadzik, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Javed Hafsa, Samantha Hagan, Jack W Hague, Rosemary Hague, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Anne Haldeos, Writaja Halder, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Emma Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Bill Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Becky-Lee Halls, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Nicola Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Sara Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, Elizabeth Hampson, Jude Hampson, Lucy Hampson, Ozan Hanci, Ian Hancock, Sadiyah Hand, Jasmine Handford, Soran Handrean, Sarah Haney, Sheharyar Hanif, E Hanison, Alison Hanlon, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Anita Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Helen Hanwell, Mazhar Ul Haq, Ala Haqiqi, Monjurul Haque, Lesley Harden, Zoe Harding, Simon Hardman, Joanna Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, Emily Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Sandra Harlow, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Fiona Harper, Heather Harper, Melanie Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Naomi Harris, Nichola Harris, Sophie Harris, Alex Harrison, David Harrison, Julie Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Heli Harvala, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Sarah Haskins, Zena Haslam, Adil Hassan, Ali Hassan, Wagae UI Hassan, Waqar Ul Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Stephanie Hatch, Jonathan Hatton, Sheryl Haviland, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Annie Hawkins, Catherine Hawkins, Nancy Hawkins, Tanya Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Tamsin Haydon, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Vanessa Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Sarah Haysom, James Hayward, Patrick Haywood, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Amy Hearn, Angela Heath, Rowan Heath, Diane Heaton, Kerry Hebbron, Gemma Hector, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Rajdeep Heire, Ulla Hemmila, Cassie Hemmings, Scott 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Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Elizabeth Hillerby, Catherine Hillman-Cooper, Elisabeth Hilton, Zoe Hilton, Sarah Hinch, Marcus Hinde, Andrew Hindle, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Alison Hirst, Jemma Hives, Benson Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Renate Hodge, Simon Hodge, Lesley Hodgen, Holly Hodgkins, Louise Hodgkinson, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Catherine Holbrook, Catherine Holden, Melinda Holden, Thomas Holder, Niels Holdhof, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Marie Hollands, Elizabeth Holliday, Nina Holling, Gillian Hollis, Laszlo Hollos, Linda Holloway, Simon Holloway, Marcus Hollyer, Amy Holman, Ann Holmes, Benjamin Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Caroline Holt, Lyndsey Holt, Siobhan Holt, Susie Holt, Alexandra Holyome, Marie Home, Toni Home, Renate Homewood, Kate Hong, Laura Hontoria del Hoyo, Clare Hooper, Sarah Hoosdally, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Daniel Hornan, Nicola Hornby, Zoey Horne, Latoya Horsford, Megan Horsford, Mark Horsford, Valana Horsham, Alexander Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Nicola Horton-Turner, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Leanne Hostler, Maxine Hough, Sarah Hough, Brittany Houghton, Catherine Houghton, Iain Houghton, Kathryn Houghton, Rebecca Houlihan, Angela Houston, Hamish Houston, Tawedzegwa Hove, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Alison Howarth, Diane Howarth, Serena Howe, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Joanne Hoyle, Josh Hrycaiczuk, Naing Zaya Htoon, Su Htwe, Ying Hu, Chiang Ooi Huah Huah, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Alex Hudson, Cara Hudson, Heather Hudson, Peter Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Eithne Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Laura Humber, Megan Hume, Charlotte Humphrey, Ismay Humphreys, Alasdair Humphries, Joanne Humphries, Lena Hunold, Fiona Hunt, Kristen Hunt, Luke Hunt, Sophie Hunt, Al Hunter, Alexandra Hunter, Isobel Hunter, Karl Hunter, Neil Hunter, George Huntington, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Yusra Husaini, Coralie Huson, Afreen Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Wasim Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Raheem Hussein, Rebecca Hussey, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Mazen Ibraheim, Abdalla Ibrahim, Ahmed Ibrahim, Asil Ibrahim, Mohamed Ibrahim, Monzeer Ibrahim, Wadah Ibrahim, Adetokunbo I Idowu, Muhammad Idrees, Hina Iftikhar, Mawara Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Mary Ilsley, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Alison Imtiaz, Haider Imtiaz, Claire Ingall, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Jennifer Inglis, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Ilian P Iordanov, Anil Ipe, Adil Iqbal, Madiha Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Jane Ireland, Robert Irons, Mohannad Irshad, Muhammad S Irshad, Janice Irvine, Val Irvine, Pamela Irving, Robert Irving, Mina Ishak, Erica Isherwood, Aminul Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, Caroline Ison, M'hamedi Israa, Sharon Isralls, Ali Issa, Monica Ivan, Catrina Ivel, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Menaka Iyer, Mia Iyer, Calum Jack, Amanda Jackson, Anthony Jackson, Ben Jackson, Beth Jackson, Douglas Jackson, Ella Jackson, Hayley Jackson, Helen Jackson, Jane Jackson, Julie Jackson, Karin Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Sharon Jackson, Nikita Jacob, Patricia Jacob, Reni Jacob, Nicola Jacques, Terri-Lisa Jacques-Brown, Anisa Jafar, Daniel Jafferji, Ali Jaffery, Chandrashekar Jagadish, Vijay Jagannathan, Sam Jaggard, Mandeep Jagpal, Fernandez R Jaime, Neemisha Jain, Seema Jain, Susan Jain, Sanjay Jaiswal, Danyal Jajbhay, Thomas Jaki, Bintou Jallow, Yusuf Jaly, Sabine Jamal, Zeba Jamal, Yasmin Jameel, Albie James, Christie James, Kate James, Lee James, Linda James, Mark James, Nicholas James, Olivia James, Rebecca James, Ruth James, Tracy James, Jack Jameson, Aaron Jamison, Phoebe Jane, Azara Janmohamed, Sabrina Jansz, Deepa Japp, Lorraine Jappy, Victor Jardim, Catherine Jardine, Emma Jarnell, Ellie Jarvie, Ann Jarvis, Claire Jarvis, Lisa Jarvis, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Mays Jawad, Lona Jawaheer, Kauky Jawaid, Anu Jayachandran, Dinakaran Jayachandran, Angelina Jayakumar, Deepak Jayaram, Ravi Jayaram, Geeshath Jayasekera, Thilina Jayatilleke, Abi Jayebalan, Saman Jeddi, Vandana Jeebun, Mohammad S Jeelani, Zeynab Jeewa, Emma Jefferson, Katie Jeffery, Helen Jeffrey, Jenni Jeffrey, Rachel Jeffrey, Sue Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, Christopher Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Jacqui Jennings, Louise Jennings, Rebecca Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge Antonio Jesus Silva, Champa Jetha, Kishan Jethwa, Jeby Jeyachandran, Visuvanathan Jeyakumar, Dharshana Jeyapalan, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Laura Jimenez, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Navin John, Sarah John, Emma Johns, Margaret Johns, Anne-Marie Johnson, Antoinette Johnson, David Johnson, Emma Johnson, Gillian Johnson, Kathryn Johnson, Katie Johnson, Luke Johnson, Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Rachel Johnson, Tracy Johnson, Zoe Johnson, Claire Johnston, Janet Johnston, Laura Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Hazel Jones, Jac Jones, James Jones, Jamie Jones, Jessica Jones, Jonathon Jones, Julie Jones, Karen Jones, Kate E Jones, Kevin Jones, Laura Jones, Laura M Jones, Lorna Jones, Louise Jones, Mathew Jones, Nicola Jones, Paul Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Taya Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Annette Jose, Sanal Jose, Anna Joseph, Joseph Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Revati Joshi, Benz Josiah, Tiffany Joyce, Adriel Ju Wen Kwek, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Katarina Kacinova, Nikhil Kadam, Rebecca Kahari, Gail Kakoullis, Azad Kala Bhushan, Richard JK Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Seika Kalsoom, Elisa Kam, John Kamara, Mohamed Kamara, Ajay Kamath, Prakash Kamath, Ravindra Kamath, Siddharth Arun Kamerkar, Nick Kametas, Musaiwale Kamfose, Arul Kandaswamy, Leia Kane, Osei Kankam, Thogulava Kannan, Abhinav Kant, Vikas Kapil, Ritoo Kapoor, Sonal Kapoor, Sourjya Kar, Janaka Kara, Vasita Kara, Marina Karakantza, Rona Kark, Nicholas Karunaratne, Natashja Kasianczuk, Vidya Kasipandian, Rizwan Kassam, Janarth Kathirgamachelvam, Victoria Katsande, Kulbinder Kaul, Daljit Kaur, Dervinder Kaur, Jasmin Kaur, Jaspreet Kaur, Satvinder Kaur, Zunaira Kausar, Mohammad AA Kawser, Andrea Kay, Sarah Kay, Jossy N Kayappurathu, Callum Kaye, Ahemd Kazeem, Naved Kazi, Sharon Kaznica, Samantha Kearley, Rachel Kearns, Nichola Kearsley, Joanne Keating, John Keating, Liza Keating, Elizabeth Keddie-Gray, Katie Keen, Natalie Keenan, Jonathan Kefas, Stephen Kegg, Laura Keith, Uzoamaka Keke, Tosin Kelani, Joanne Kellett, Jeremy Kellington, Alison Kelly, Conor Kelly, David Kelly, Diane Kelly, Dominic Kelly, Emma Kelly, Laura Kelly, Martin Kelly, Michael Kelly, Rosalind Kelly, Sinead Kelly, Stephen Kelly, Thomas Kelly, Mary Kelly-Baxter, Marketa Keltos, Timothy Kemp, Kelly Kemsley, Alexandra Kendall-Smith, Sarah Kennard, Ann Kennedy, Caroline Kennedy, James Kennedy, Sophie Kennedy-Hay, Julia Kenny, Kelly Kent, Melanie Kent, Lynne Keogan, Alexander Keough, Clement Kerlin, A Kerr, Andrew Kerr, Maria Kerr, Caroline Kerrison, Anthony Kerry, Samantha Kershaw, Helen Kerslake, Ian Kerslake, Helen Kerss, Jocelyn Keshet-Price, Margaret Kevern, Georgina Keyte, Abdul Khadar, Ali Khalid, Muhammad U Khalid, Syed Khalid, Amir Khalil, Asma Khalil, Sijjad Khalil, Abubakar Khan, Ali Khan, Al-Imran Khan, Arham Khan, Asad Khan, Aurangzeb Khan, Burhan Khan, Camran Khan, Fatimah Khan, Kausik Khan, Malik Aamaz Khan, Marria Khan, Mehrunnisha Khan, Mohammad Khan, Mohammed Khan, Nayeem Khan, Omar Khan, Rahe Khan, Rahila Khan, Sabiya Khan, Shabana Khan, Shahul Khan, Shoaib Khan, Tasaduksultan Khan, Waseem Khan, Usman F Khatana, Jibran Khatri, Jyoti Khatri, Hafiza Khatun, Taslima Khatun, Mena Kheia, Jacyntha Khera, Htet Ei Khin, Najaf Khoja, Kiran Khokhar, Jayne Khorsandi, Chloe Khurana, Faith Kibutu, Andrew Kidd, Michelle Kidd, Joe Kidney, Shane Kidney, Will Kieffer, James Kilbane, Caroline Kilby, Eileen Killen, Susan Kilroy, Bomee Kim, Jee Whang Kim, Sarah Kimber, Andy King, Barbara King, Jennifer King, Kirsten King, Rachel King, Sarah King, Tony King, Victoria King, Emily King-Oakley, Laura Kingsmore, Andy King-Venables, Fiona Kinney, Sidra Kiran, Jeremy Kirk, Jodie Kirk, Daniel Kirkbride, Amy Kirkby, Ian Kirker, Emily Kirkham, Gemma Kirkman, Ursula Kirwan, Kelly Kislingbury, Toby Kitching, Laura Kitto, Lauren Kittridge, Sarah Klaczek, Frieder Kleemann, Susan Kmachia, Chris Knapp, Lucy Knibbs, Alicia Knight, Fraser Knight, Marian Knight, Sarah Knight, Steven Knight, Tom Knight, Ellen Knights, Jane Knights, Toby Knights, Martin Knolle, Carol Knott, Charlotte Knowles, Karen Knowles, Laurence Knowles, Emily Knox, Lucy Knox, Oliver Koch, Ronan Kodituwakku, Gouri Koduri, Aisha Koirata, Eirene Kolakaluri, Magdalena Kolodziej, Eirini Kolokouri, Keith Kolsteren, Samantha Kon, Niladri Konar, Mari Kononen, Athanasios Konstantinidis, Hui Fen Koo, Imogen Koopmans, Emmanuela Kopyj, Laura Korcierz, James Korolewicz, George Koshy, Chris Kosmidis, Jalpa Kotecha, Easwari Kothandaraman, Leonidas Koukouflis, Koushan Kouranloo, Rukhsana Kousar'c, Margarita Kousteni, Maja Kovac, Alex Kozak Eskenazia, Kestutis Krasauskas, Raghu Krishnamurthy, Vinodh Krishnamurthy, Manju Krishnan, Hari Krishnan, Suzanne Krizak, Sean Krupej, Agnieszka Kubisz-Pudelko, Soren Kudsk-Iversen, Aurimas Kudzinskas, Chirag Kukadiya, Nainesha Kulkarni, Aditi Kumar, Mayur Kumar, Ramesh Kumar, Ravi Kumar, Rita Kumar, Rupa Kumar, Satish Kumar, Vimal Kumar, Arun Kundu, Heinke Kunst, Amit Kurani, Mohammed Kurdy, Rincy Kurian, Vimal Kurmars, Cameron Kuronen-Stewart, Ranganai S Kusangaya, Vlad Kushakovsky, Mandy Kuunal, Apexa Kuverji, Amma Kyei-Mensah, Thyra Kyere-Diabour, Moe Kyi, Nyan M Kyi, Laura Kyle, Karali-Tsilimpari Kyriaki, Julius Labao, Louise Lacey, Nikki Lack, Emma Ladlow, Heather Lafferty, Shondipon Laha, Sushil Lahane, Clement Lai, James Lai, Emma Laing, Robert Laing, Inez Laing-Faiers, Emily Laity, Michelle Lake, Nicki Lakeman, David Lalloo, Fiona Lalloo, Alison Lam, Fiona Lamb, Lucy Lamb, Thomas Lamb, Nick Lambe, Pauline Lambert, Claudia Lameirinhas, Mohammed KG Lami, Abigail Lamikanra, Holly Lamont, Michal Lamparski, Djillali Lamrani, Christine Lanaghan, Rebecca Lanaway, Ivone Lancona-Malcolm, Julia Lancut, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Alidih Lang, Stephen Lang, Daniel Langer, Margaret Langley, Charles Langoya, Emily Langthorne, Taiya Large, Wojciech Lason, Anna Last, Scott Latham, John Latham-Mollart, Afzal Latheef, Darren Latimer, Nang Latt, Carly-Jane Lattimore, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jennifer Law, Jessica Law, Penny Law, Richard Law, Colin Lawler, Mark Lawley, Emma Lawrence, Jo Lawrence, Neil Lawrence, Ryan Lawrie, Jemima Lawson, Joanne Lawson, Louise Lawson, Rebecca Lawton, Michael Lay, Christine Laycock, Reina Layug, Maria Lazo, Vietland Le, Amelia Lea, William Lea, Ian Leadbitter, Thomas Leahy, Richard Lean, Lorna Leandro, Darren Leaning, Sandra Leason, Christina Leaver, Marie Anne Ledingham, Emma Lee, Hannah Lee, Irish Lee, Judith Lee, Sam Lee, Shi Han Lee, Simon Lee, Sindy Lee, Stephanie Lee, Tracey Lee, Xiang Lee, Diana Lees, Jennifer Lees, Helen Legge, Julian Leggett, Katie Leigh-Ellis, Kevan Leighton, Nicky Leitch, Eleni Lekoudis, Petula Lemessy, Nicholas Lemoine, Joana Lemos, Irina Lenchuk, Katy Leng, Katrina Lennon, Liz Lennon, Isabel Lentell, Kelly Leonard, Wen Leong, Nicky Leopold, Oskar Lepiarczyk, Isla Leslie, Eleni Lester, Joe Leung, Ullrich Leuschner, Emma Levell, Chris Levett, Alice Lewin, Michaela Lewin, Alison Lewis, David Lewis, Dee Lewis, Georgina Lewis, Gillian Lewis, Joanne Lewis, Joseph Lewis, Kathryn Lewis, Keir Lewis, Leon Lewis, Lisa Lewis, Marissa Lewis, Rob Lewis, Robert Lewis, Catherine Lewis-Clarke, Lorraine Lewis-Prosser, Katherine Lewiston, Adam Lewszuk, Penny Lewthwaite, Samantha Ley, Anna Li, Jenny Li, Angela Liao, Victoria Licence, David Lieberman, Susan 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Kateryna Macconaill, Chloe Macdonald, Stuart MacDonald, Tania MacDonald, Claire Macfadyen, James G Macfarlane, Jill Macfarlane, Laura Macfarlane, Cara MacGuigan, Lisa MacInnes, Iain MacIntyre, Jill MacIntyre, Kirsten Mack, Callum Mackay, Euan Mackay, Laura Mackay, Alexander Mackenzie, Matt Mackenzie, Robert MacKenzie Ross, Ami Mackey, Patricia Mackey, Fiona Mackie, Robert Mackie, Carolyn Mackinlay, Claire Mackintosh, Katherine Mackintosh, Sheila MacLennan, Mary Joan MacLeod, Michael Macmahon, Andrew MacNair, Catherine Macphee, Iain Macpherson, Catriona Macrae, Allan MacRaild, Eilidh MacVean, Alannah Madden, Mary Madden, Norman Madeja, Karen Madgwick, Pradeep Madhivathanan, Madhavi Madhusudhana, Harriet Madiyiko, Alpha Madu, Lorraine Madziva, Marion Mafham, Nick Magee, Frederick Magezi, Tim Maggs, Negar Maghsoodi, Christopher Magier, Marios Magriplis, Kathryn Maguire, Natasha Mahabir, Subramanian Mahadevan-Bava, Anjanie Maharajh, Ajit Mahaveer, Bal Mahay, Kanta Mahay, Hibo Mahdi, Thushika Mahendiran, Siva Mahendran, Sarah Maher, Anistta Maheswaran, Shameera Maheswaran, Tina Maheswaran, Parisa Mahjoob-Afag, Ahmed Mahmood, Farhana Mahmood, Waheed Mahmood, Zahra Mahmood, Hager Mahmoud, Ewan Mahony, Luke Mair, Toluwani Majekdunmi, Kesson Majid, Rupert Major, Jaydip Majumdar, Mohammad KH Majumder, Stephen Makin, Marius Malanca, Hannah Malcolm, Flora Malein, Neeraj Malhan, Ayesha Malik, Gulshan Malik, Mohammed Maljk, Paul Mallett, Petrina Mallinder, Georgia Mallison, Louise Mallon, Edward Malone, Gracie Maloney, Edgar Malundas, Madhu Mamman, Irene Man, Kathy Man, Rossana Mancinelli, Marco Mancuso-Marcello, Tracy Manders, Lauren Manderson, Justin Mandeville, Roope Manhas, Carmen Maniero, Ravi Manikonda, Bobby Mann, Jonathan Manning, Lynne Mannion, Katherine Mansi, Katarina Manso, Dina Mansour, Isheunesu T Mapfunde, Predeesh Mappa, Hemant Maraj, Garikayi Marange, Lisa March, Clare Marchand, Neil Marcus, Maria Marecka, Gomathi Margabanthu, Jordi Margalef, Lavinia Margarit, Georgios Margaritopoulos, Mike Margarson, Fernandez M Maria del Rocio, Teresa Maria Pfyl, Victor Mariano, Helen Maria-Osborn, Ashleigh Maric, Grace Markham, John Markham, Maria Marks, Pamela Marks, Elisabeth Marouzet, Arran Marriott, Cheryl Marriott, Nemonie Marriott, Brian Marsden, Karen Marsden, Paul Marsden, Sarah Marsden, Tracy Marsden, Robyn Marsh, Adam Marshall, Andrew Marshall, Gail Marshall, Henry Marshall, Jaimie Marshall, James Marshall, Jenna Marshall, Nicola Marshall, Riley Marshall, Jennifer Marshall, Samantha Marston, Emmeline Martin, Hayley Martin, Hope Martin, Jane Martin, Karen Martin, Kate Martin, Laila Martin, Michael Martin, Noelia Martin, Tim Martin, Winston Martin, Sarah Martin, Tim Martindale, Marcus Martineau, Alexander Martinez, Lauren Martinez, Jose Carlos Martinez Garrido, Juan Martin-Lazaro, Olivia Martins, Lucas Martins Ferreira, Vijay Kumar Maruthamuthu, Gemma Maryan, Roman Mary-Genetu, Sam Maryosh, Vidan Masani, Diego Maseda, Sheila Mashate, Yasaman Mashhoudi, Al Mashta, Izhaq Masih, Sanna Masih, Nick Maskell, Perry Maskell, Matthew Masoli, Lynn Mason, Rebecca Mason, Richard Mason, Ruth Mason, Claire Mason, Mohammad Masood, Mohammad T Masood, Syed Masood, Syed SME Masood, Aaqib Masud, Lear Matapure, Cristina Matei, Ropafadzo Matewe, Manraj Matharu, Stephy Mathen, Alex Mather, Nicole Mather, Jonathan Mathers, Joanna Matheson, Amal Mathew, Anna Mathew, Moncy Mathew, Verghese Mathew, Caroline Mathews, Jesha Mathews, Kate Mathias, Marion Mathie, Darwin Matila, Wadzanai Matimba-Mupaya, Nashaba Matin, Elina Matisa, Max Matonhodze, Elijah Matovu, Jaysankar Mattappillil, Alison J Matthews, Heather Matthews, Helen Matthews, Sue Matthews, Gwynn Matthias, Fiona Maxton, Adam Maxwell, Gemma Maxwell, Veronica Maxwell, James May, Joanne May, Oliver May, Philippa May, Irving Mayanagao, Matthew Maycock, Graham Mayers, Lee Maynard, Shelley Mayor, Ibreaheim Mazen, Andrea Mazzella, Nyambura Mburu, Mercy Mbwembwe, Martyn McAdam, Eleanor McAleese, Helinor McAleese, Paul McAlinden, Audrey McAlpine, Graeme McAlpine, Jonathan McAndrew, Hamish McAuley, Sarah McAuliffe, Claire McBrearty, Carole McBride, Erin McBride, Michael McBuigan, James McBurney, Laura McCabe, Amanda McCairn, Martina McCalmont, Jake McCammon, Nicole McCammon, Conor McCann, Alexandra McCarrick, Brendan McCarron, Eoghan McCarthy, Michelle McCarthy, Natalie McCarthy, Sinead McCaughey, Gareth McChlery, Tara McClay, Beverley McClelland, Declan McClintock, Patricia McCormack, Jacqueline McCormick, Wendy McCormick, Paul McCourt, Jame McCrae, Sharon McCready, Allison McCreath, Gordan McCreath, Helen McCreedy, Louise McCreery, Iain J McCullagh, Josephine McCullagh, Liz McCullagh, Megan McCullagh, Conor McCullough, Katherine McCullough, Nicola McCullough, Sarah McCullough, Fiona McCurrach, Rory McDermott, Katharine McDevitt, Helen McDill, Basil McDonald, Claire McDonald, Debbie McDonald, Rob McDonald, Sam McDonald, Damhnaic McDonald, Rowan McDougall, Irene 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Mollet, Malid Molloholli, Aoife Molloy, April Molloy, Linda Molloy, Andrew Molyneux, Tasnim Momoniat, Holly Monaghan, Josephine Monaghan, Krista Monaghan, Shiva Mongolu, Katelyn Monsell, Mahmoud Montasser, Alan Montgomery, Hugh Montgomery, Prebashan Moodley, Ian Moody, Margaret Moody, Nick Moody, Angela Moon, James Moon, Ji-Hye Moon, Maria Moon, May Moonan, Parvez Moondi, Alex Moore, Carly Moore, Christopher Moore, Davidjar Moore, Faye Moore, Gillian Moore, Hannah Moore, Judith Moore, Laura Moore, Sally Moore, Sonia Moore, Tracy Moore, Rachel Moores, Ed Morab, Jose Morales, Nuria Moramorell, Louise Moran, Grishma Moray, Jeronimo Moreno-Cuesta, Adam Morgan, Amy Morgan, Christine Morgan, Colin Morgan, Jackie Morgan, Lauren Morgan, Leila Morgan, Matthew Morgan, Patrick Morgan, Katie Morgan-Jones, Emily Morgan-Smith, Anna Morley, Thomas Morley, Wendy Morley, Anna Morris, Damian Morris, Fiona Morris, Helen Morris, Juliet Morris, Katie Morris, Laura Morris, Lucy Morris, Mary-Anne Morris, Niall Morris, Paul Morris, Sheila Morris, Susan Morris, Douglas Morrison, Moira Morrison, Mary Morrissey, Anna Morrow, Chantal Morrrell, Franca Morselli, Gordon Mortem, Chelsea Morton, Gordon Morton, Rosna Mortuza, Priti Morzaria, Alison Moss, Charlotte Moss, Rachel Moss, Sarah Moss, Stuart Moss, Nicki Motherwell, Johanna Mouland, Caroline Moulds, Hilary Moulton, Lorraine Mounsey, Elizabeth Mousley, Karen Moxham, Borja Moya, Quberkani Moyo, Eunice Mshengu, Sheila Mtuwa, Ali Muazzam, Iqtedar A Muazzam, Nykki Muchenje, Dalia Mudawi, Girish Muddegowda, Imran Mugal, Ahsan Mughal, Javaid Muglu, Javed Muhammad, Alison Muir, Carol Muir, Martin Muir, Dipak Mukherjee, Syed Asim Ali Mukhtar, Denise Mukimbiri, Tshinupay Mukwa, Peter Mulgrew, Ben Mulhearn, Arafat Mulla, Dee Mullan, Dileepkumar Mullasseril Kutten, Niall Mullen, Rosemary Mullett, Sandra Mulligan, Barbara Mullin, Joanne Mullings, Lana Mumelj, Andrew Mumford, Sarah Mumford, Mohammed Munavvar, Henry Munby, Anne-Marie Munro, Sheila Munt, Nafissah Munu, McDonald Mupudzi, Arshid Murad, Oluwatosin H Muraina, Koteshwara Muralidhara, Diane Murdoch, Mhairi Murdoch, Jennifer Murira, Alison Murphy, Carl Murphy, Emily Murphy, Fidelma Murphy, Gail Murphy, Jo Murphy, Peter Murphy, Sheenagh Murphy, Simon Murphy, Clare Murray, David Murray, Eleanor Murray, Katie Murray, Kenneth Murray, Lisa Murray, Lorna Murray, Tracey Murray, Eoin Murtagh, Mithun Murthy, Catherine Murton, Rosie Murton, Neeka Muru, Rosemary Musanhu, Maimuna Mushabe, Kaiser Mushtaq, Omaisa Mushtaq, Ahmed M Mustafa, Elhaytham Mustafa, Mustafa Mustafa, Ibrahim Mustapha, Zhain Mustufvi, Callum Mutch, Eric Mutema, Balakumar Muthukrishnan, Sheree Mutton, Natasha Muzengi, Memory Mwadeyi, Bettina Mwale, Esther Mwaura, Raji Myagerimath, Alice Myers, Sam Myers, Khin Swe Myint, Yadee Myint, Libor Myslivecek, Helen Nabakka, Evelyn Nadar, Iftikhar Nadeem, Moosa Nadheem, Asma Naeem, Hassan Naeem, Salman Naeem, Samraiz Nafees, Mohamed Nafei, Parminder Naga, Thapas Nagarajan, Imrun Nagra, Deepak Nagra, Mina Naguib, Kirushthiga Naguleswaran, K Shonit Nagumantry, Kevin Naicker, Sarveshni Naidoo, Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Sri Nallapareddy, Soum Nallapeta, Arumugan Nallasivan, Uttam Nanda, Aarti Nandani, Ali Raza Naqvi, Asadullah Naqvi, Sara Naqvi, Shruthi Narayan, Sophia Nasa, Dominic Nash, Nader Nasheed, Abdul Nasimudeen, Umer Nasir, Marwan Nassari, Tahir Nasser, Anushka Natajaran, Anuja Natarajan, Geetha Natarajan, Nalin Natarajan, Nikhila Natarajan, Rajkumar Natarajan, Noel Nathaniel, Mala Nathvani, Priyan Nathwani, George Nava, Neena Navaneetham, Jeya Navaratnam, Helen Navarra, Sadaf Naveed, John Navin, Khuteja Nawaz, Sarfaraz Nawaz, Shasta Nawaz, Bonilla Nayar, Suzanne Naylor, Moez Nayyar, Farrah Naz, Mobeena Naz, Salima Nazarali, Babak Nazari, S Nazir, Sehar Nazir, Dumisani Ncomanzi, Onyine Ndefo, Alan Neal, Elaine Neary, Mostafa Negmeldin, Paula Neill, Hector E Neils, Avideah Nejad, Louise Nel, Marie Nelson, Richard Nelson, Scott Nelson, Rajesh Nemane, Samiksha Nepal, Daniel Nethercott, Kimberley Netherton, Kimberley Nettleton, Claire-Michelle Neville, Tracy Nevin, Josephine Newanji, Alison Newby, Angela Newby, David Newby, Tracy Newcombe, Charlotte Newman, Diana Newman, Julie Newman, Oscar Newman, Richard Newman, Tabitha Newman, Thomas Newman, Rachel Newport, Claire Newsam, Christopher Newson, Maria Newton, Anthony YKC Ng, Ka Wing Ng, Maxine Ng, Sarah Ng, Wee Jin Ng, Thomas Ngan, Gabriel CE Ngui, Alice Ngumo, Caoimhe Nic Fhogartaigh, Nathalie Nicholas, Philip Nicholas, Rachel Nicholas, Teresa Nicholas, Donna Nicholls, Lisa Nicholls, Alice Nicholson, Anne Nicholson, Annette Nicholson, Janet Nicholson, Ian Nickson, Eileen Nicol, Elizabeth Nicol, Rebecca Nicol, Pantelis Nicola, Antony Nicoll, Pantzaris Nikolaos, Georgii Nikonovich, Annette Nilsson, Kofi Nimako, Louise Nimako, Camus Nimmo, Preethy Ninan, Mahesh Nirmalan, Muhammad Nisar, Toby 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Sudershan, Lee Sudlow, Gayle Sugden, Peter Sugden, Rudresh Sukla, Ali Suliman, Fatimah Suliman, Ian Sullivan, Sugrah Sultan, Jennifer Summers, Mark Summerton, Samyukta Sundar, Reka Sundhar, Edmond Sung, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Shilpa Suresh, Rachel Suri, Michael Surtees, Danielle Suter, Helen Sutherland, Rachel Sutherland, Rebecca Sutherland, Dovile Sutinyte, Deborah Sutton, John Sutton, Sam Sutton, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Thomas Swaine, Christopher Swales, Lorna Swan, Nicola Swarbrick, Tirion Swart, Stephen Sweetman, Samaher Sweity, Ealish Swift, Paul Swift, Pauline Swift, Peter Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Omair Syed, Catriona Sykes, Daisy Sykes, Eliot Sykes, Luke Sylvester, Dominic Symon, Andrew Syndercombe, Zoe Syrimi, Jen Syson, Gemma Szabo, Tamas Szakmany, Megan Szekely, Matthew Szeto, Maria Tadros, Amr Tageldin, Lucy Tague, Hasan Tahir, Muhammad Tahir, Silvia Taibo, Zsofia Takats, Abigail Takyi, Peter Talbot, Alison Talbot -Smith, James Talbot-Ponsonby, Richard Tallent, Bradley Tallon, Phoebe Tamblin-Hopper, Adrian Tan, Bee T Tan, Hock Tan, Huey Tan, Jade Tan, Keith Tan, WeiTeen Tan, Anand Tana, Xiaohui Tang, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Ran Tao, Mark Taplin, Hayley Tarft, Priyal Taribagil, Obaid Tarin, Syed Tariq, Zeeshan Tariq, David Tarpey, Lisa Tarrant, Antonia Tasiou, Elizabeth Tatam, Margaret L Tate, Kate Tatham, Vera Tavoukjian, Alexander Taylor, Beverley Taylor, Brian Taylor, Charlie Taylor, Charlotte Taylor, David Taylor, Elisabeth Taylor, Janet Taylor, Jennifer Taylor, Joanne Taylor, Julie Taylor, Karen Taylor, Leanne Taylor, Margaret Taylor, Matthew Taylor, Melanie Taylor, Natalie Taylor, Rachael Taylor, Rachel Taylor, Samantha Taylor, Suzanne Taylor, Tina Taylor, Tracey Taylor, Vicky Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Jessica Teasdale, Julie Tebbutt, Caroline Tee, Rajni Tejwani, Seble Tekle, Adam Telfer, Vibha Teli, Jennifer Tempany, Holly Templar, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Lynne Terrett, Louise Terry, Abbi Tervit, Dariusz Tetla, Kate Tettmar, Shirish Tewari, Daniel Tewkesbury, Joana Texeira, ChiaLing Tey, Clare Thakker, Manish Thakker, Amirtharajh Tharmakulasingam, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Lambrini Theocharidou, Phyu Thet, Kapeendran Thevarajah, Mayooran Thevendra, Nang Thiri Phoo, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Andrew Thomas, Caradog Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Hannah Thomas, Helen Thomas, James Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Samantha Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Rhian Thomas-Turner, Samantha Thomas-Wright, Catherine Thompson, Christopher Thompson, Clara Thompson, Fiona Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Luke Thompson, Michael Thompson, Orla Thompson, Rebecca Thompson, Roger Thompson, Trevor Thompson, Usilla Thompson, Nicola Thomson, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Wendy Thorne, Jim Thornton, Michael Thornton, Richard Thornton, Sara Thornton, Susan Thornton, Thomas Thornton, Tracey Thornton, Allison Thorpe, Christopher Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Elisha Thuesday, Vicky Thwaiotes, Guy Thwaites, Simon Tiberi, Jane Tidman, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Amanda Tiller, John Timerick, Elizabeth Timlick, Alison Timmis, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Helen Tivenan, Helen T-Michael, Anne Todd, Jackie Todd, Stacy Todd, Mohamed Tohfa, Helena Tollick, Melanie Tolson, Ana Luisa Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Jo Tomlinson, James Tonkin, Ivan Tonna, Catherine Toohey, Kirsty Topham, Mathew Topping, Ruhaif Tousis, Peter Tovey, Gareth Towersey, Jason Towler, Jill Townley, Alain Townsend, Chris Townsend, Richard Tozer, Claire Tranter, Helen Tranter, Jonathan Trattles, Christopher Travill, Sarah Traynor, Karis Treuberg, Mike Trevett, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Thomas Trimble, Alex Trimmings, Tom Trinick, Sven Troedson, Emily Tropman, Amy Trotter, Madeleine Trowsdale Stannard, Nigel Trudgill, Maria Truslove, Shaun Trussell, Tariq Trussell, Sara Tryon, Kyriaki Tsakiridou, Christine Tsang, Hoi Pat Tsang, Peter Tsang, Tan Tsawayo, Kyriaki Karali Tsilimpari, Georgios Tsinaslanidis, Simon Tso, Sally Tucker, Victoria Tuckley, Caroline Tuckwell, Aisha Tufail, Redmond Tully, Grace Tunesi, Saidat Turawa, Killiam Turbitt, Anna Turco, Krystyna Turek, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, David Turner, Frances Turner, Gail Turner, Kate Turner, Kelly Turner, Louise Turner, Lucy Turner, Marc Turner, Mark Turner, Patricia Turner, Ruth Turner, Sally Turner, Samantha Turner, Susan Turner, Victoria Turner, Sharon Turney, Jon Turvey, Conor Tweed, David Tweed, Rebecca Twemlow, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Mohammad S Uddin, Ruhama Uddin, Ruzena Uddin, Salamat Ullah, Sana Ullah, Sanda Ullah, Athavan Umaipalan, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Ben Ummat, Charlotte Underwood, Jonathan Underwood, Laura Unitt, Adam Unsworth, Jasvinder Uppal, Veerpal S Uppal, James Uprichard, Gerry Upson, Masood Ur Rasool, Alison Uriel, Sebastian Urruela, Hiromi Uru, Miranda Usher, Rebecca Usher, Alex UsherRea, Andrew Ustianowski, Jane Uttley, Linda C Vaccari, Uddhav Vaghela, Abhay Vaidya, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Pramodh Vallabhaneni, Pedro Valle Vallines, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Joseph Vance-Daniel, Rama Vancheeswaran, Caryn Vander Riet, Samuel I Vandeyoon, Padma Vankayalapati, Piyush Vanmali, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Kate Vardigans, Stehen J Vardy, Anu Varghese, Maria Varghese, William Varney, Giulia Varnier, Valeria Vasadi, Olivia Vass, Vimal Vasu, Vasanthi Vasudevan, Manu Vatish, Heloyes Vayalaman, Christopher Vaz, Niki Veale, Sachuda Veerasamy, Bar Velan, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Anitha Velusamy, Ian Venables, Mavi Venditti, David Veniard, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Lyn Ventilacion, Joanne Vere, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Rachel Vernall, Britney Vernon, Mark Vertue, Jerik Verula, Natalie Vethanayagam, Lucy Veys, Carinna Vickers, Saji Victor, Jennifer Vidler, Wayne Vietri, Bavithra Vijayakumar, Vinod Warrier Vijayaraghavan Nalini, Brigita Vilcinskaite, Neringa Vilimiene, Sudharkar Vimalanathan, Lynn Vinall, Sylvia Vinay, Latha Vinayakarao, Rachel Vincent, Rosie Vincent, Pritpal Virdee, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Jeyakumar Visuvanathan, Karunakaran Vithian, Sorice Vittoria, Elena Vlad, Ben Vlies, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Kirsten Wadsworth, Syed EI Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Abiodun Waheed Adigun, Sawan Waidyanatha, Rachel Wake, Alice Wakefield, William Wakeford, Michelle Wakelin, Fiona Wakinshaw, Andrew Walden, Jane Walden, Lorna Walding, Alexandria Waldron, Gemma Walker, Harriet Walker, Ian Walker, Jasmine Walker, Kevin Walker, Kim Walker, Linda Walker, Marie T Walker, Olivia Walker, Rachel Walker, Rebecca Walker, Susan Walker, Derek Wallbank, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Fiona Waller, Rosemary Waller, Gabiel Wallis, Gabriel Wallis, Louise Wallis, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Thin Wan, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Deborah Warbrick, Samantha Warburton, Deborah Ward, Emma Ward, Joanna Ward, Karen Ward, Luke Ward, Nicola Ward, Rachael Ward, Rebecca Ward, Thomas Ward, Tom Ward, Scott A Warden, Adele Wardle, Karen Wardle, Steve Wardle, Hassan Wardy, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Yolanda Warren, Hannah Warren-Miell, Gill Warwick, Charlotte Washington, Helen Wassall, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Nick Watkins, Abigail Watson, Adam JR Watson, Ekaterina Watson, Eleanor Watson, Paul Watson, Rebecca Watson, Robert Watson, Sandra Watson, Malcolm Watters, Donna Watterson, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Paul Weaver, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Tim Webster, Kathleen Wedgeworth, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Lauren Wentworth, Kate Wesseldine, James Wesson, Jim Wesson, Adam West, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Abbie White, Andrew White, Benjamin White, Christopher White, Duncan White, Emily White, James White, Jonathan White, Katie White, Marie White, Nick White, Sarah White, Sonia White, Stephen White, Tracey White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Sophie Whiteley, Victoria Whiteside, Drew Whitley, Kaitlyn Whitley, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Andrew Whittingham Hirst, Ashley Whittington, Helen Whittle, Robert Whittle, Suzanne Whyte, Eunice Wiafe, Lou Wiblin, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Ritchie Wildman, Tracey Wildsmith, Joe Wileman, Donna Wiles, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Chloe Wilkes, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Helen Wilkinson, Holly Wilkinson, Iain Wilkinson, Lesley Wilkinson, Martin Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, James Williams, Jayne Williams, Jennie Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Marie Williams, Matthew Williams, Patricia Williams, Penny Williams, Rachael Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Tamanna Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Rachel Williamson, Helen Williamson, Bruce Willian, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Laura Willmott, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Alison Wilson, Andrea Wilson, Antoinette Wilson, Billy Wilson, Catherine Wilson, Eve Wilson, James Wilson, Karen Wilson, Kate Wilson, Lucinda Wilson, Mark Wilson, Matthew Wilson, Toni Wilson, Evie Wiltsher, Marlar Win, Tin Win, Wut Yee Win Win, Lucinda Winckworth, Laura Winder, Piers Winder, Phillip Windrum, Kerry Winham-Whyte, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Pascal Winter, Barbara Winter-Goodwin, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Holly Wissett, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Magda Wolna, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Edwin Wong, Jessica Sue Yi Wong, Kit Y Wong, Lee Wong, Mei Yin Wong, Nick Wong, Sam Wong, Yun Man Wong, Amanda Wood, Caroline Wood, Carrie Anne Wood, Dianne Wood, Fiona Wood, Hannah Wood, Jennifer Wood, Joe Wood, Julia Wood, Kathryn Wood, Lisa Wood, Louise Wood, Michelle Wood, Stephen Wood, Tracy Wood, Ursula Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Luke Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Debra Woods, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Rachel Wookey, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Tim Wreford-Bush, Joanne Wren, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Imogen Wright, Lee Wright, Lianne Wright, Pete Wright, Rachel Wright, Rebecca Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Retno Wulandari, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Zhongyang Xia, Huiyuan Xiao, Masseh Yakubi, May Yan, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Naairah Yaqub, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Julie Yates, Mark Yates, Charlotte Yearwood Martin, Andrew Yeatman, Khin Yein, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Richard Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Raisa Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Lynn Zarb, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Marian Zelman, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Veronica Zindonda, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Roslin Zuha, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, Will Zuurbier, Sheba Zyengi, and University of St Andrews. School of Medicine
Subjects: Male, Convalescent plasma, medicine.medical_treatment, 030204 cardiovascular system & hematology, Antibodies, Viral, Rate ratio, 0302 clinical medicine, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Medicine, Hospital Mortality, 030212 general & internal medicine, 11 Medical and Health Sciences, Aged, 80 and over, Medicine(all), Mortality rate, Covid19, Articles, 3rd-DAS, General Medicine, Middle Aged, Hospitals, Treatment Outcome, Female, Open label, Coronavirus Infections, Life Sciences & Biomedicine, RM, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Humans, In patient, Pandemics, COVID-19 Serotherapy, Aged, Mechanical ventilation, Science & Technology, SARS-CoV-2, business.industry, Significant difference, Immunization, Passive, COVID-19, Length of Stay, NIS, R1, Respiration, Artificial, United Kingdom, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, business
Abstract: Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Published: 2021
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20. Blood group type A secretors are associated with a higher risk of COVID‐19 cardiovascular disease complications

Author: Marie Attwood, Jennifer Pooley, Catherine Hyams, Fiona Moghaddas, David J. Anstee, Adam Finn, Gabriella Ruffino, Nicola Cogan, Faroakh Hosseini, Alex Cooper, David T Arnold, Luned Nichols, Belinda K. Singleton, Gyongyver Gyorffy, Ashley M. Toye, Claire Asby, Pedro Luis Moura, Christian J Stevens-Hernandez, Alan R. Noel, Sabine Kupzig, Fergus Hamilton, and Tosti J. Mankelow
Subjects: medicine.medical_specialty, Fucosyltransferase, Coronavirus disease 2019 (COVID-19), biology, business.industry, Covid19, Disease, Group A, Asymptomatic, Gastroenterology, Virus, law.invention, fluids and secretions, law, Internal medicine, ABO blood group system, biology.protein, Medicine, medicine.symptom, Sickle Cell, Thrombosis, and Haematology, business, Research Articles, Polymerase chain reaction, Research Article
Abstract: The SARS‐CoV‐2 virus causes COVID‐19, an infection capable of causing severe disease and death but which can also be asymptomatic or oligosymptomatic. We investigated whether ABO blood group or secretor status was associated with COVID‐19 severity. We investigated secretor status because expression of ABO glycans on secreted proteins and non‐erythroid cells are controlled by a fucosyltransferase (FUT2), and inactivating FUT2 mutations result in a non‐secretor phenotype which protects against some viral infections. Data combined from healthcare records and our own laboratory tests (n = 275) of hospitalized SARS‐CoV‐2 polymerase chain reaction positive patients confirmed higher than expected numbers of blood group A individuals compared to O (RR = 1.24, CI 95% [1.05, 1.47], p = 0.0111). There was also a significant association between group A and COVID‐19‐related cardiovascular complications (RR = 2.56, CI 95% [1.43, 4.55], p = 0.0011) which is independent of gender. Molecular analysis revealed that group A non‐secretors are significantly less likely to be hospitalized than secretors. Testing of convalescent plasma donors, among whom the majority displayed COVID‐19 symptoms and only a small minority required hospitalization, group A non‐secretors were slightly over‐represented. Our findings showed that group A non‐secretors are not resistant to infection by SARS‐CoV‐2, but are more likely to experience a less severe form of associated disease.
Published: 2021
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21. Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict progression of diabetic kidney disease

Author: Michael J. Donovan, Lili Chan, Gohar Mosoyan, Fergus Fleming, Michael W. Kattan, Patricia Connolly, James R. McCullough, Joseph A. Vassalotti, Girish N. Nadkarni, Fadi Salem, Steven G. Coca, Scott M. Damrauer, and Barbara Murphy
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030232 urology & nephrology, Renal function, Kidney Function Tests, Article, Cohort Studies, Machine Learning, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, Positive predicative value, Internal Medicine, medicine, Electronic Health Records, Humans, Electronic data, Diabetic Nephropathies, 030212 general & internal medicine, Diabetic kidney disease, Aged, Aged, 80 and over, Creatinine, Framingham Risk Score, business.industry, Middle Aged, medicine.disease, Prognosis, United States, chemistry, Disease Progression, Biomarker (medicine), Female, business, Prediction, Biomarkers, Kidney disease, Cohort study, Glomerular Filtration Rate
Abstract: Aim Predicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX™) combining electronic health records (EHR) and biomarkers. Methods This is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for predicting a composite outcome of eGFR decline of ≥5 ml/min per year, ≥40% sustained decline, or kidney failure within 5 years. Results In 1146 patients, the median age was 63 years, 51% were female, the baseline eGFR was 54 ml min−1 [1.73 m]−2, the urine albumin to creatinine ratio (uACR) was 6.9 mg/mmol, follow-up was 4.3 years and 21% had the composite endpoint. On cross-validation in derivation (n = 686), KidneyIntelX had an AUC of 0.77 (95% CI 0.74, 0.79). In validation (n = 460), the AUC was 0.77 (95% CI 0.76, 0.79). By comparison, the AUC for the clinical model was 0.62 (95% CI 0.61, 0.63) in derivation and 0.61 (95% CI 0.60, 0.63) in validation. Using derivation cut-offs, KidneyIntelX stratified 46%, 37% and 17% of the validation cohort into low-, intermediate- and high-risk groups for the composite kidney endpoint, respectively. The PPV for progressive decline in kidney function in the high-risk group was 61% for KidneyIntelX vs 40% for the highest risk strata by KDIGO categorisation (p event for the high-risk group was 41% (p Conclusions KidneyIntelX improved prediction of kidney outcomes over KDIGO and clinical models in individuals with early stages of DKD. Graphical abstract
Published: 2021

22. Breast cancer risk factors and survival by tumor subtype

Author: Päivi Auvinen, Hoda Anton-Culver, Stig E. Bojesen, Gad Rennert, Christos Petridis, Taru A. Muranen, Lukas Schwentner, Jenny Chang-Claude, Chen-Yang Shen, Melissa A. Troester, Sara Y. Brucker, Miriam Dwek, Jingmei Li, Nadia Obi, Montserrat Garcia-Closas, Soo Hwang Teo, Pascal Guénel, Hidemi Ito, Sabine Behrens, Rulla M. Tamimi, Melissa C. Southey, Michelle D. Holmes, Christopher A. Haiman, Henrik Flyger, Roger L. Milne, Per Hall, Jyh-Cherng Yu, Thomas U. Ahearn, William G. Newman, D. Gareth Evans, Dong-Young Noh, Qin Wang, Robert Winqvist, Tjoung-Won Park-Simon, Angela Cox, Dimitrios Mavroudis, Federico Canzian, Celine M. Vachon, Annelie Augustinsson, Shivaani Mariapun, Keitaro Matsuo, Mia M. Gaudet, Anna Jakubowska, Loic Le Marchand, Rob A. E. M. Tollenaar, Paul D.P. Pharoah, Mikael Hartman, Jane Heyworth, Alison M. Dunning, Daniele Campa, Keun-Young Yoo, Anna Morra, Sileny Han, Anna H. Wu, David J. Hunter, Laura E. Beane Freeman, Mehdi Manoochehri, Volker Arndt, Elinor J. Sawyer, Peter A. Fasching, Alicja Wolk, Xiao-Ou Shu, José A. García-Sáenz, Hermann Brenner, Børge G. Nordestgaard, Pooja Middha Kapoor, Diether Lambrechts, Kamila Czene, Marjanka K. Schmidt, Nadege Presneau, Stephen J. Chanock, Mervi Grip, Ignacio Briceño, Stella Koutros, Nicola J. Camp, Kathleen M. Egan, Wei Zheng, Reiner Hoppe, Simon S. Cross, James V. Lacey, Manjeet K. Bolla, Cari M. Kitahara, Annika Lindblom, Carl Blomqvist, William J. Tapper, Diana Torres, Jan Lubinski, Milena Jakimovska, Vessela N. Kristensen, Jose E. Castelao, Graham G. Giles, Andrew F. Olshan, John L. Hopper, A. Heather Eliassen, Valerie Rhenius, Christopher G. Scott, Agnes Jager, Thilo Dörk, Justin A. Williams, Ian Tomlinson, Emmanouil Saloustros, Ji Yeob Choi, Dijana Plaseska-Karanfilska, Thérèse Truong, Audrey Y. Jung, Daehee Kang, Argyrios Ziogas, Peter Kraft, Arto Mannermaa, Rudolf Kaaks, Heiko Becher, Wolfgang Janni, Niclas Håkansson, Steven N. Hart, Xiaohong R. Yang, Håkan Olsson, Fergus J. Couch, Renske Keeman, Ute Hamann, Atocha Romero, Daniel O. Stram, Andreas Schneeweiss, Susan M. Gapstur, Michael Lush, Diana Eccles, Sara Margolin, Hedy S. Rennert, Muhammad Usman Rashid, Mitul Shah, Matthias W. Beckmann, Sophia S. Wang, Douglas F. Easton, Manuela Gago-Dominguez, Christine L. Clarke, and Medical Oncology
Subjects: 0301 basic medicine, Oncology, Adult, medicine.medical_specialty, Epidemiology, Estrogen receptor, Breast Neoplasms, Article, 03 medical and health sciences, Aged, Cause of Death, Female, Humans, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prospective Studies, Risk Factors, Survival Analysis, Life Style, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, business.industry, Proportional hazards model, Cancer, medicine.disease, Confidence interval, 3. Good health, Tumor Subtype, 030104 developmental biology, Clinical research, 030220 oncology & carcinogenesis, business, Body mass index
Abstract: Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus 0– Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
Published: 2021
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23. Synchronous Melanoma and Pancreas Malignancies Leading to a Discovery of a CDKN2A Mutation in a Patient with No Known Family History

Author: Mary O'Reilly, Ray Mc Dermott, and Fergus Keane
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, pancreatic cancer, malignant melanoma, Case Report, Malignancy, lcsh:RC254-282, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, CDKN2A, Internal medicine, Pancreatic cancer, Carcinoma, Medicine, Family history, synchronous primary malignancies, business.industry, cdkn2a mutation, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Adenocarcinoma, business, genetic predisposition
Abstract: We report a case of a 60-year-old male with metachronous primary malignancies, pancreatic cancer and malignant melanoma which recurred simultaneously. Both cancers were challenging to diagnose and throughout the case at different times, the presence of two active malignancies obscured the clinical picture. A bleeding gastric lesion found in the stomach 6 months after a distal pancreatectomy for pancreatic adenocarcinoma revealed metastatic melanoma, presumed secondary from a melanoma excised from the patient’s back 2 years previously. During surgery intended to resect the gastric lesion, peritoneal nodularity was identified, with histology confirming metastatic pancreas cancer. This case highlights two main points of interest. Firstly it emphasises the role for consideration of a genetic predisposition in young patients with more than one primary malignancy. The man in this case was not informed of his family history as he was adopted. If he had knowledge of previous family history, he may have been able to provide information to expedite arrival at the diagnosis of a CDKN2A mutation (melanoma-pancreatic carcinoma syndrome). In addition, this case also raises the issue of the challenges we face when treating synchronous primary malignancies. The two malignancies here behaved equally aggressively and posed obstacles for treatment as there is no mutual method of carcinogenesis that could be targeted with treatment; therefore, treatment modalities had to be chosen to treat each malignancy separately. To date, studies evaluating the role for targeted therapy in the setting of CDKN2A mutations have not conclusively provided meaningful benefits to patients.
Published: 2021
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24. Neuropsychiatric symptoms associated with cerebral small vessel disease: a systematic review and meta-analysis

Author: Fergus N. Doubal, Daniel Gilmartin, Angela C. C. Jochems, Lucy Knox, Joanna M. Wardlaw, and Una Clancy
Subjects: medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Internal medicine, Humans, Medicine, Dementia, Apathy, 030212 general & internal medicine, Vascular dementia, Stroke, Fatigue, Biological Psychiatry, business.industry, Mental Disorders, Odds ratio, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Cerebral Small Vessel Diseases, Meta-analysis, Delirium, Anxiety, medicine.symptom, business
Abstract: Summary Background Cerebral small vessel disease, a common cause of vascular dementia, is often considered clinically silent before dementia or stroke become apparent. However, some individuals have subtle symptoms associated with acute MRI lesions. We aimed to determine whether neuropsychiatric and cognitive symptoms vary according to small vessel disease burden. Methods In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and PsycINFO for articles published in any language from database inception to Jan 24, 2020. We searched for studies assessing anxiety, apathy, delirium, emotional lability, fatigue, personality change, psychosis, dementia-related behavioural symptoms or cognitive symptoms (including subjective memory complaints), and radiological features of cerebral small vessel disease. We extracted reported odds ratios (OR), standardised mean differences (SMD), and correlations, stratified outcomes by disease severity or symptom presence or absence, and pooled data using random-effects meta-analyses, reporting adjusted findings when possible. We assessed the bias on included studies using the Risk of Bias for Non-randomized Studies tool. This study is registered with PROSPERO, CRD42018096673. Findings Of 7119 papers identified, 81 studies including 79 cohorts in total were eligible for inclusion (n=21 730 participants, mean age 69·2 years). Of these 81 studies, 45 (8120 participants) reported effect estimates. We found associations between worse white matter hyperintensity (WMH) severity and apathy (OR 1·41, 95% CI 1·05–1·89) and the adjusted SMD in apathy score between WMH severities was 0·38 (95% CI 0·15–0·61). Worse WMH severity was also associated with delirium (adjusted OR 2·9, 95% CI 1·12–7·55) and fatigue (unadjusted OR 1·63, 95% CI 1·20–2·22). WMHs were not consistently associated with subjective memory complaints (OR 1·34, 95% CI 0·61–2·94) and unadjusted SMD for WMH severity between these groups was 0·08 (95% CI −0·31 to 0·47). Anxiety, dementia-related behaviours, emotional lability, and psychosis were too varied or sparse for meta-analysis; these factors were reviewed narratively. Overall heterogeneity varied from 0% to 79%. Only five studies had a low risk of bias across all domains. Interpretation Apathy, fatigue, and delirium associated independently with worse WMH, whereas subjective cognitive complaints did not. The association of anxiety, dementia-related behaviours, emotional lability, and psychosis with cerebral small vessel disease require further investigation. These symptoms should be assessed longitudinally to improve early clinical detection of small vessel disease and enable prevention trials to happen early in the disease course, long before cognition declines. Funding Chief Scientist Office of the Scottish Government, UK Dementia Research Institute, Fondation Leducq, Stroke Association Garfield-Weston Foundation, Alzheimer's Society, and National Health Service Research Scotland.
Published: 2021
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25. 30 Informant-Reported Decline Associates with Silent Acute Stroke Lesions and Worse Small Vessel Disease in Mild Stroke Patients

Author: Carmen Arteaga, Iona Hamilton, Rosalind Brown, Joanna M. Wardlaw, Michael S. Stringer, Will Hewins, Stewart Wiseman, Una Clancy, Fergus N. Doubal, Gordon W. Blair, Daniela Jaime Garcia, M Valdes-Hernadez, Dominic Job, Michael J. Thrippleton, and Francesca M Chappell
Subjects: Aging, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Mild stroke, Montreal Cognitive Assessment, Magnetic resonance imaging, General Medicine, Disease, medicine.disease, Embolism, Internal medicine, medicine, Cardiology, Dementia, Small vessel, Geriatrics and Gerontology, business, Acute stroke
Abstract: Introduction Small vessel disease (SVD) commonly causes stroke and dementia. Early clinical predictors of disease progression are lacking. We aimed to determine whether informant reports of chronic cognitive/functional decline, prerequisites for dementia diagnosis, are associated with (a)baseline SVD burden, measured by Fazekas scores and (b)SVD change, measured by incident subcortical Diffusion-weighted Imaging (DWI) lesions. Method We prospectively recruited patients with mild ischaemic stroke, performed diagnostic MRI, and invited participants to repeat MRI 3- to 6-monthly. Informants completed the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) prior to baseline visit, a 16-item questionnaire which assesses patients’ cognitive and functional decline in the preceding ten years. Scores range from 1–5: a score above 3.3 has high sensitivity/specificity for dementia post-stroke. We conducted linear regression with IQCODE as the dependent variable, adjusting for age, sex, baseline MoCA, disability (modified Rankin Scale). Results We recruited 106 participants (mean age 67 years;range 40–86;33% female). Ninety-three informant questionnaires were returned. IQCODE associated with baseline Fazekas score; Fazekas 6 (β = 0.28, p = 0.04) vs. Fazekas 3 (β = 0.03, p = 0.67), R2 = 0.11, adjusted for age, sex, baseline MoCA, disability. Incident DWI lesions were common (15/106; 14/15 subcortical; no active embolic sources; median 67 days post-stroke). Four were asymptomatic, two reported stroke-like symptoms and nine had neuropsychiatric/non-focal symptoms. IQCODE was higher in those with a new lesion vs. without (β = 0.21, p = 0.02), R2 = 0.09, while age (β = −0.004, p = 0.19), MoCA (β = −0.006, p = 0.56) and disability (β = 0.06, p = 0.2) were not. Conclusions Higher SVD burden and incident, mostly “silent” stroke lesions associate more strongly with informant concerns of cognitive/functional decline than age or objective cognitive tests. These findings are novel in an ischaemic stroke population and the first to assess IQCODE/SVD progression. Future work should determine whether combining informant reports with imaging features of small vessel disease improves early detection of dementia.
Published: 2021
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26. Germline BRCA1/2 mutations and severe haematological toxicities in patients with breast cancer treated with neoadjuvant chemotherapy

Author: Valentina Nekljudova, Christian Jackisch, Kerstin Rhiem, Jenny Furlanetto, Volker Möbus, Rita K. Schmutzler, Jens Huober, Jens Uwe Blohmer, Peter Klare, Bianca Lederer, Christoph Salat, Kristina Lübbe, Theresa Link, Fergus J. Couch, Eric Hahnen, Peter A. Fasching, Claus Hanusch, Ingo Bauerfeind, Michael Untch, Sibylle Loibl, Dirk Michael Zahm, Hans Tesch, Bernd Gerber, and Andreas Schneeweiss
Subjects: Adult, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Triple Negative Breast Neoplasms, Neutropenia, Risk Assessment, Gastroenterology, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Risk Factors, Germany, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Anthracyclines, Chemotherapy-Induced Febrile Neutropenia, Germ-Line Mutation, Randomized Controlled Trials as Topic, BRCA2 Protein, Chemotherapy, Taxane, BRCA1 Protein, business.industry, Odds ratio, Middle Aged, medicine.disease, Hematologic Diseases, Thrombocytopenia, Neoadjuvant Therapy, Confidence interval, Treatment Outcome, 030104 developmental biology, Oncology, chemistry, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Taxoids, business, medicine.drug
Abstract: BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities.Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed. Primary objective was the rate of neutropenia grade (G)III-IV in cycle 1 (C1). Secondary objectives included effects on overall and other haematological toxicities GIII-IV in C1, cumulative haematological toxicity across all cycles, relative total dose intensity, and granulocyte-colony stimulating factor prophylaxis. Haematological toxicities under taxanes, carboplatin, and cyclophosphamide were explored.Two hundred nine of 1171 (17.8%) evaluated patients had gBRCA1/2m. In C1, 37.4% gBRCA1/2m versus 35.7% wild-type patients had neutropenia GIII-IV (P = 0.683). For C1, gBRCA1/2m predicted neither for neutropenia GIII-IV (odds ratio [OR]: 1.26, 95% confidence intervals [CI]: 0.87-1.82, P = 0.226) nor for other haematological toxicities GIII-IV (OR: 0.91, 95% CI: 0.64-1.31, P = 0.625) in multivariable regression models. Analyses of cumulative toxicities across all cycles yielded similar results except thrombocytopaenia GIII-IV, which was increased in gBRCA1m patients. In patients treated with taxanes, the rate of haematological toxicities GIII-IV was higher in gBRCA1/2m compared with wild-type (59.5% versus 43.1%; p 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies.gBRCA1/2m was not associated with higher risk of overall severe haematological toxicities in the first cycle or cumulatively across all cycles under standard chemotherapy for TNBC. Under taxane, patients with gBRCA1/2m might have a higher risk of haematological toxicities GIII-IV, requiring further research.
Published: 2021
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27. Pulmonary metastasectomy in colorectal cancer: A letter in response to Antonoff and colleagues

Author: Fergus Macbeth, Joel Dunning, and Tom Treasure
Subjects: Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, Internal medicine, medicine, Metastasectomy, medicine.disease, business
Published: 2022

28. Targeted care navigation to reduce hospital readmissions in ‘at‐risk’ patients

Author: Velandai Srikanth, Iain Edwards, Carolina D Weller, Gary Braun, Fergus McGee, Ruth Azzopardi, Rebecca K Pang, David A. Snowdon, Belinda Berry, and Nadine E. Andrew
Subjects: Matching (statistics), medicine.medical_specialty, business.industry, Hazard ratio, Hazard, Confidence interval, Acute care, Emergency medicine, Propensity score matching, Cohort, Internal Medicine, Medicine, business, Health department
Abstract: BACKGROUND Care navigation is commonly used to reduce preventable hospitalisation. The use of Electronic Health Record derived algorithms may enable better targeting this intervention for greater impact. OBJECTIVE To evaluate if community-based Targeted Care Navigation, supported by an Electronic Health Record derived readmission risk algorithm, is associated with reduced rehospitalisation. METHODS A propensity score matched cohort (5 comparison to 1 intervention cohort ratio) study was conducted in an 850-bed Victorian public metropolitan health service, Australia, from May to November 2017. Admitted acute care patients with a non-surgical condition, identified as at-risk of hospital readmission using an Electronic Health Record derived readmission risk algorithm provide by the state health department, were eligible. Targeted Care Navigation involved telephone follow-up support provided for 30-days post-discharge by a Registered Nurse. The hazard ratio for hospital readmission was calculated at 30-, 60-, and 90-days post-discharge using multivariable Cox Proportional Hazards regression. RESULTS Sixty-five recipients received care navigation and were matched to 262 people who did not receive care navigation. Excellent matching was achieved with standardised differences between groups being
Published: 2022
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29. ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence

Author: John W. Gregory, Fergus J. Cameron, Kriti Joshi, Mirjam Eiswirth, Christopher Garrett, Katharine Garvey, Shivani Agarwal, and Ethel Codner
Subjects: Consensus, Diabetes Mellitus, Type 1, Endocrinology, Adolescent, Endocrinology, Diabetes and Metabolism, Pediatrics, Perinatology and Child Health, Internal Medicine, Humans, Practice Patterns, Physicians', Societies, Medical
Published: 2022

30. Decreased occurrence of ketoacidosis and preservation of beta cell function in relatives screened and monitored for type 1 diabetes in Australia and New Zealand

Author: John M. Wentworth, Helena Oakey, Maria E. Craig, Jennifer J. Couper, Fergus J. Cameron, Elizabeth A. Davis, Antony R. Lafferty, Mark Harris, Benjamin J. Wheeler, Craig Jefferies, Peter G. Colman, and Leonard C. Harrison
Subjects: Endocrinology, Diabetes and Metabolism, Pediatrics, Perinatology and Child Health, Internal Medicine
Abstract: Islet autoantibody screening of infants and young children in the Northern Hemisphere, together with semi-annual metabolic monitoring, is associated with a lower risk of ketoacidosis (DKA) and improved glucose control after diagnosis of clinical (stage 3) type 1 diabetes (T1D). We aimed to determine if similar benefits applied to older Australians and New Zealanders monitored less rigorously.DKA occurrence and metabolic control were compared between T1D relatives screened and monitored for T1D and unscreened individuals diagnosed in the general population, ascertained from the Australasian Diabetes Data Network.Between 2005 and 2019, 17,105 relatives (mean (SD) age 15.7 (10.8) years; 52% female) were screened for autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2. Of these, 652 screened positive to a single and 306 to multiple autoantibody specificities, of whom 201 and 215, respectively, underwent metabolic monitoring. Of 178 relatives diagnosed with stage 3 T1D, 9 (5%) had DKA, 7 of whom had not undertaken metabolic monitoring. The frequency of DKA in the general population was 31%. After correction for age, sex and T1D family history, the frequency of DKA in screened relatives was80% lower than in the general population. HbA1c and insulin requirements following diagnosis were also lower in screened relatives, consistent with greater beta cell reserve.T1D autoantibody screening and metabolic monitoring of older children and young adults in Australia and New Zealand, by enabling pre-clinical diagnosis when beta cell reserve is greater, confers protection from DKA. These clinical benefits support ongoing efforts to increase screening activity in the region and should facilitate the application of emerging immunotherapies.
Published: 2022

31. Hybrid closed‐loop therapy with a first‐generation system increases confidence and independence in diabetes management in youth with type 1 diabetes

Author: Alison, Roberts, Leanne, Fried, Julie, Dart, Martin, de Bock, Janice, Fairchild, Bruce, King, Geoffrey R, Ambler, Fergus, Cameron, Sybil A, McAuley, Anthony C, Keech, Alicia, Jenkins, David N, O Neal, Elizabeth A, Davis, Timothy W, Jones, and Mary B, Abraham
Subjects: Adult, Blood Glucose, Young Adult, Diabetes Mellitus, Type 1, Insulin Infusion Systems, Endocrinology, Adolescent, Blood Glucose Self-Monitoring, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Hypoglycemic Agents, Insulin
Abstract: Hybrid closed-loop (HCL) therapy improves glycaemic control in adolescents with type 1 diabetes; however, little is known about their lived experience using these systems. The aim of this study was to explore the lived experiences of youth with type 1 diabetes using HCL therapy, and their parents, to provide insight into their lived experiences.Adolescents and young adults aged 12-25 years, who used Medtronic MiniMed™ 670G HCL system during a 6-month randomised clinical trial, and their parents, were invited to participate in a semi-structured interview at the end of the study. Open-ended questions were used to explore the lived experiences of families using HCL. The interviews were audio-recorded, transcribed and analysed using thematic analysis to determine the main themes.In all, 17 young people with type 1 diabetes mean ± SD age: 17.5 ± 4.2 years, diabetes duration: 11.0 ± 4.9 years and HbABoth youth and parents acknowledged the benefits of this first-generation HCL system in improving glycaemic outcomes and in providing flexibility and independence. These lived experiences provide valuable information in the introduction and provision of targeted education with HCL therapy.
Published: 2022
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32. Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women

Author: Kathryn J. Ruddy, Qin Wang, Joe Dennis, Stacey J. Winham, Janet E. Olson, Thomas U. Ahearn, Rachel A. Murphy, Wing-Yee Lo, David J. Hunter, Manjeet K. Bolla, Douglas F. Easton, Derrick G. Lee, Marike Gabrielson, Gareth D. Evans, Nick Orr, Reiner Hoppe, Minouk J. Schoemaker, Paul L. Auer, Michael Lush, Andrew F. Olshan, Kristan J. Aronson, Ross L. Prentice, Argyrios Ziogas, Martha S. Linet, Melissa C. Southey, Robert J. MacInnis, Michael Jones, Nicole L. Larson, Elke M van Veen, Anthony Howell, Alison M. Dunning, Christopher A. Haiman, Peter Kraft, William G. Newman, Loic Le Marchand, Lauren R. Teras, Jenny Chang-Claude, Mikael Eriksson, Irene L. Andrulis, Graham G. Giles, Heiko Becher, Montserrat Garcia-Closas, Thomas Brüning, A. Heather Eliassen, Pascal Guénel, Cari M. Kitahara, Pooja Middha Kapoor, Hoda Anton-Culver, Niclas Håkansson, Emilie Cordina-Duverger, Xiaoliang Wang, Stephen J. Chanock, Christopher J. Scott, Anthony J. Swerdlow, Ute Krüger, Sara Lindström, Roger L. Milne, Alpa V. Patel, Kristen Brantley, Annelie Augustinsson, Rulla M. Tamimi, Lynne R. Wilkens, Celine M. Vachon, Alicja Wolk, Håkan Olsson, Fergus J. Couch, Ute Hamann, Philippe Wagner, Kamila Czene, Audrey Y. Jung, Rudolf Kaaks, Claire Mulot, Laure Dossus, Angela Brooks-Wilson, Kyriaki Michailidou, Per Hall, Jonine D. Figueroa, Thérèse Truong, Charles M. Perou, Melissa A. Troester, Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Dennis, Joe [0000-0003-4591-1214]
Subjects: Oncology, Male, medicine.medical_specialty, Hormone Replacement Therapy, 631/208/205/2138, Hormone Replacement Therapy/adverse effects, Breast Neoplasms, Genome, Text mining, Breast cancer, SDG 3 - Good Health and Well-being, 692/699/67/2324, Risk Factors, Internal medicine, medicine, Breast Neoplasms - chemically induced - epidemiology - genetics, Humans, Breast, Breast Neoplasms/chemically induced, Medicinsk genetik, Cancer och onkologi, Multidisciplinary, business.industry, Estrogen Replacement Therapy, Hormone Replacement Therapy - adverse effects, article, Estrogen Replacement Therapy/adverse effects, Estrogen Replacement Therapy - adverse effects, medicine.disease, Cancer and Oncology, 692/699/67/1347, Female, Menopausal hormone therapy, Menopause, business, Medical Genetics, 692/499
Abstract: Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.
Published: 2022
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33. 19-OR: KidneyIntelX Association with Clinical Outcomes in Diabetic Kidney Disease

Author: GIRISH N. NADKARNI, DIPTI TAKALE, BRUCE NEAL, KENNETH W. MAHAFFEY, YSHAI YAVIN, MICHAEL K. HANSEN, FERGUS FLEMING, HIDDO L. HEERSPINK, and STEVEN COCA
Subjects: Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Individuals with diabetic kidney disease (DKD) are at risk for progression, heart failure, and death. We assessed the association of KidneyIntelX, a bioprognostictest validated for DKD progression, with a composite time-to-event endpoint of 57% eGFR decline, kidney failure, heart failure hospitalization (HFH) , or death in a posthoc analysis of a subgroup of CANVAS participants with DKD. sTNFR-1, sTNFR-2, and KIM-1 were measured via proprietary assays, and KidneyIntelX scores were calculated using the existing algorithm. Hazard ratios for high vs. low-risk strata for the composite outcome were adjusted for age, sex, race, treatment arm, baseline CVD, HbA1c, SBP, DBP, LDL, BMI) . During 5.6 years follow-up, 282 (22%) of the 1278 CANVAS participants with DKD experienced the outcome (57% decline in eGFR/ESKD 3%, HFH 6%, death 16%) . The adjusted HR for the composite outcome in KidneyIntelX high-risk group was 2.7 (95% CI 1.9 to 3.8) vs. the low-risk group. Canagliflozin reduced the risk for the composite event vs. placebo, with larger absolute risk reductions for the high-risk stratum (11%) , compared to intermediate (6%) or low-risk strata (4%) (p In conclusion, KidneyIntelX successfully risk-stratified adults with DKD for clinical outcomes. Absolute risk reductions with canagliflozin were greatest in the high-risk stratum, thereby potentially allowing its use to identify patients most likely to benefit from treatment. Disclosure G.N.Nadkarni: Advisory Panel; Renalytix, Consultant; AstraZeneca, Reata Pharmaceuticals, Inc., Renalytix, Siemens, Other Relationship; Renalytix, Stock/Shareholder; Renalytix. D.Takale: None. B.Neal: Other Relationship; Janssen Research & Development, LLC. K.W.Mahaffey: Consultant; Novo Nordisk. Y.Yavin: Employee; Janssen Research & Development, LLC. M.K.Hansen: Employee; Janssen Research & Development, LLC. F.Fleming: Employee; Renalytix. H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. S.Coca: Advisory Panel; 3ive Labs, Nuwellis, Reprieve Cardiovascular, Consultant; Axon Therapies, Bayer AG, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Stock/Shareholder; pulseData, Renalytix. Funding Renalytix
Published: 2022
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34. Impact of Personalized Genetic Breast Cancer Risk Estimation With Polygenic Risk Scores on Preventive Endocrine Therapy Intention and Uptake

Author: Christina Kim, Lonzetta Neal, Lori A. Thicke, Julian O. Kim, Debjani Grenier, Andrew Cooke, Benjamin A Goldenberg, Jason P. Sinnwell, Amy C. Degnim, Fergus J. Couch, Linda Hasadsri, Daniel J. Schaid, Sandhya Pruthi, Celine M. Vachon, and Daniela L. Stan
Subjects: Adult, Counseling, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Aftercare, Breast Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Genetic breast cancer, Risk Factors, Internal medicine, Biomarkers, Tumor, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Precision Medicine, skin and connective tissue diseases, Aged, Estimation, Aromatase Inhibitors, business.industry, Incidence, Incidence (epidemiology), Endocrine therapy, Middle Aged, medicine.disease, 030104 developmental biology, Genetic Loci, 030220 oncology & carcinogenesis, Female, Polygenic risk score, Risk assessment, business
Abstract: Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer–Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median (range) age, 56.1 (36.0–76.4 years)]. Median 10-year and lifetime IBIS risks were 7.9% and 25.3%. Inclusion of PRS increased lifetime IBIS breast cancer risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased breast cancer risk by PRS, 39 (41.9%) had greater intent to take endocrine therapy; of those with decreased breast cancer risk by PRS, 28 (46.7%) had less intent to take endocrine therapy (P < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy (P < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; P < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed.Prevention Relevance: Counseling women at increased breast cancer risk using polygenic risk score (PRS) risk estimates can significantly impact preventive endocrine therapy uptake. Further development of PRS testing to personalize breast cancer risk assessments and endocrine therapy counselling may serve to potentially reduce the incidence of breast cancer in the future.
Published: 2021
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35. Association of mammographic density measures and breast cancer 'intrinsic' molecular subtypes

Author: Aaron D. Norman, Rulla M. Tamimi, Christopher G. Scott, Celine M. Vachon, Kimberly A. Bertrand, Yunn Yi Chen, Fergus J. Couch, Steven R. Cummings, John A. Shepherd, Fang Fang Wu, V. Shane Pankratz, Matthew R. Jensen, Karla Kerlikowske, Kathleen R. Brandt, Stacey J. Winham, Geffen Kleinstern, and Daniel W. Visscher
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Estrogen receptor, Breast Neoplasms, Logistic regression, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, Progesterone receptor, Biomarkers, Tumor, medicine, Humans, Aged, Breast Density, business.industry, MAMMOGRAPHIC DENSITY, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 030104 developmental biology, Receptors, Estrogen, Case-Control Studies, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, business, Body mass index
Abstract: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of “intrinsic” molecular breast cancer (BC) subtypes. We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women
Published: 2021
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36. Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction

Author: Anuradha Lala, Sean Pinney, Empa-Tropism (Atru ) Investigators, M. Urooj Zafar, Alvaro Garcia-Ropero, Javier Sanz, Icilma V. Fergus, Juan J. Badimon, Carlos G. Santos-Gallego, Vivian M. Abascal, Valentin Fuster, Juan Antonio Requena-Ibanez, Mercè Roqué, Donna M. Mancini, Ariana P. Vargas-Delgado, Ronald Tamler, Pedro R. Moreno, Fernando Sabatel-Perez, Farah Atallah-Lajam, Frank Macaluso, Cathleen Varley, Samantha Sartori, Johanna Contreras, and Anderly Rodriguez-Cordero
Subjects: Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Glucosides, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Clinical endpoint, medicine, Empagliflozin, Humans, 030212 general & internal medicine, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, End-systolic volume, Aged, Heart Failure, Ejection fraction, business.industry, Stroke Volume, Middle Aged, medicine.disease, Cardiac Imaging Techniques, Heart failure, Exercise Test, Quality of Life, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients.In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p 0.001). Patients who received empagliflozin had significant improvements in peak OEmpagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).
Published: 2021
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37. Effect of Germline Mutations in Homologous Recombination Repair Genes on Overall Survival of Patients with Pancreatic Adenocarcinoma

Author: Thanh P. Ho, Eric C. Polley, Robert R. McWilliams, William R. Bamlet, Steven N. Hart, Kari G. Rabe, Nicholas J. Boddicker, Pashtoon Murtaza Kasi, Fergus J. Couch, Chunling Hu, Siddhartha Yadav, Kun Y. Lee, Gloria M. Petersen, Tricia Lindstrom, and Rohan Gnanaolivu
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, PALB2, Adenocarcinoma, medicine.disease_cause, Article, Germline, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, BARD1, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Genetic Testing, Prospective Studies, Germ-Line Mutation, Aged, Mutation, business.industry, BRIP1, Recombinational DNA Repair, Middle Aged, Prognosis, medicine.disease, Pancreatic Neoplasms, Survival Rate, DNA Repair Enzymes, 030104 developmental biology, 030220 oncology & carcinogenesis, RAD51C, Female, business, Follow-Up Studies
Abstract: Purpose:To compare the clinical characteristics and overall survival (OS) of germline mutation carriers in homologous recombination repair (HRR) genes and noncarriers with pancreatic ductal adenocarcinoma (PDAC).Experimental Design:Germline DNA from 3,078 patients with PDAC enrolled in a prospective registry at Mayo Clinic between 2000 and 2017 was analyzed for mutations in 37 cancer predisposition genes. Characteristics and OS of patients with mutations in eight genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51C, and RAD51D) involved in HRR were compared with patients testing negative for mutations in all 37 genes.Results:The 175 HRR mutation carriers and 2,730 noncarriers in the study had a median duration of follow-up of 9.9 years. HRR mutation carriers were younger (median age at diagnosis: 63 vs. 66 years, P < 0.001) and more likely to have metastatic disease at diagnosis (46% vs. 36%, P = 0.004). In a multivariable model adjusting for sex, age at diagnosis, and tumor staging, patients with germline HRR mutations had a significantly longer OS compared with noncarriers [HR, 0.83; 95% confidence interval (CI), 0.70–0.97; P = 0.02]. Further gene-level analysis demonstrated that germline ATM mutation carriers had longer OS compared with patients without germline mutations in any of the 37 genes (HR, 0.72; 95% CI, 0.55–0.94; P = 0.01).Conclusions:This study demonstrates that germline mutation carrier status in PDAC is associated with longer OS compared with noncarriers. Further research into tumor biology and response to platinum-based chemotherapy in germline mutation carriers with PDAC are needed to better understand the association with longer OS.
Published: 2020
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38. Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes

Author: Scott T Chiesa, John E. Deanfield, Timothy W. Jones, Jennifer J Couper, M. Loredana Marcovecchio, Elizabeth A. Davis, Sally M. Marshall, Denis Daneman, Paul Z. Benitez-Aguirre, Fergus J. Cameron, H. Andrew W. Neil, David B. Dunger, R Neil Dalton, Kim C. Donaghue, Maria E. Craig, and Farid H. Mahmud
Subjects: Male, medicine.medical_specialty, Adolescent, Angiotensin-Converting Enzyme Inhibitors, Pulse Wave Analysis, law.invention, Vascular Stiffness, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Endothelial dysfunction, Reactive hyperemia, Pulse wave velocity, Glycated Hemoglobin, Type 1 diabetes, business.industry, medicine.disease, Lipids, C-Reactive Protein, Diabetes Mellitus, Type 1, Creatinine, Cardiology, Arterial stiffness, Drug Therapy, Combination, Female, Endothelium, Vascular, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Cohort study
Abstract: An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0–7.2] versus 5.3% [4.7–5.9]; P =0.005), whereas no effect was observed following statin use (6.2% [5.5–6.8] versus 5.8% [5.1–6.4]; P =0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8–5.9] versus 6.3% [5.8–6.7] for high-risk versus low-risk groups; P =0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment ( P >0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03–0.12]; P =0.001 and 0.5 m/s [0.4–0.6]; P Registration— URL: https://www.clinicaltrials.gov ; Unique identifier NCT01581476.
Published: 2020
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39. Association of prior lymphopenia with mortality in pneumonia: a cohort study in UK primary care

Author: Hamilton, Fergus, Arnold, David, and Payne, Rupert
Subjects: medicine.medical_specialty, Lymphocyte, Population, Primary care, Cohort Studies, primary care, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, pneumonia, infections, 030212 general & internal medicine, education, Retrospective Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, Primary Health Care, Proportional hazards model, business.industry, Research, Pneumonia, lymphopenia, respiratory, medicine.disease, United Kingdom, medicine.anatomical_structure, Increased risk, biomarker, Biomarker (medicine), Family Practice, business, Cohort study
Abstract: BackgroundLymphopenia (reduced lymphocyte count) during infections, such as pneumonia, is common and is associated with increased mortality. Little is known about the relationship between lymphocyte count before developing infections and mortality risk.AimTo identify whether patients with lymphopenia who develop pneumonia have increased risk of death.Design and settingA cohort study set in the Clinical Practice Research Datalink (CPRD) linked to national death records, in primary care. This database is representative of the UK population and is extracted from routine records.MethodPatients aged >50 years with a pneumonia diagnosis were included from January 1998 until January 2019. The relationship between lymphocyte count and mortality was measured, using a time-to-event (multivariable Cox regression) approach, adjusted for age, sex, social factors, and potential causes of lymphopenia. The primary analysis used the most recent test before pneumonia. The primary outcome was 28-day, all-cause mortality.ResultsA total of 40 909 participants with pneumonia were included, with 28 556 having had a lymphocyte count test before pneumonia (median time between test and diagnosis was 677 days). When lymphocyte count was categorised (0–1 × 109 cells/L, 1–2 × 109 cells/L, 2–3 × 109 cells/L, >3 × 109 cells/L, never tested), both 28-day and 1-year mortality varied significantly: 14%, 9.2%, 6.5%, 6.1%, and 25%, respectively, for 28-day mortality, and 41%, 29%, 22%, 20%, and 52% for 1-year mortality. In multivariable Cox regression, lower lymphocyte count was consistently associated with increased hazard of death.ConclusionLymphopenia is an independent predictor of mortality in primary care pneumonia. Even low–normal lymphopenia (1–2 × 109 cells/L) is associated with an increase in short- and long-term mortality compared with higher counts.
Published: 2020
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40. Multicentre randomised controlled trial on virtual chromoendoscopy in the detection of neoplasia during colitis surveillance high-definition colonoscopy (the VIRTUOSO trial)

Author: Pradeep Bhandari, Sreedhari Thayalasekaran, Fergus Chedgy, Sharmila Subramaniam, Kesavan Kandiah, James Brown, Marietta Iacucci, Samuel C. Smith, Carole Fogg, and Gaius Longcroft-Wheaton
Subjects: Adult, Male, medicine.medical_specialty, Colon, Colorectal cancer, Biopsy, Colonoscopy, Withdrawal time, Gastroenterology, Chromoendoscopy, law.invention, Young Adult, Randomized controlled trial, chronic ulcerative colitis, colonoscopy, law, Internal medicine, medicine, Humans, Colitis, Early Detection of Cancer, Aged, Aged, 80 and over, Intraepithelial neoplasia, medicine.diagnostic_test, business.industry, Endoscopy, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, Crohn's colitis, Dysplasia, Colonic Neoplasms, surveillance, Female, business, colorectal neoplasia, Colonography, Computed Tomographic
Abstract: BackgroundLongstanding colonic IBD increases the risk of developing colorectal cancer. The utility of chromoendoscopy with standard-definition white light technology has been established. However, the use of high-definition virtual chromoendoscopy (HDV) in colitis surveillance remains undefined.ObjectiveTo compare the performance of HDV (i-scan OE mode 2) with high-definition white light (HDWL) for detection of neoplasia in patients with IBD undergoing surveillance colonoscopy. Additionally, we assessed the utility of protocol-guided quadrantic non-targeted biopsies.DesignA multioperator randomised controlled trial was carried out in two centres in the UK. Total of 188 patients (101 men, mean age 54) with longstanding ulcerative or Crohn’s colitis were randomised, prior to starting the surveillance colonoscopy, to using either HDV (n=94) or HDWL (n=94) on withdrawal. Targeted and quadrantic non-targeted biopsies were taken in both arms per-randomisation protocol. The primary outcome was the difference in neoplasia detection rate (NDR) between HDV and HDWL.ResultsThere was no significant difference between HDWL and HDV for neoplasia detection. The NDR was not significantly different for HDWL (24.2%) and HDV (14.9%) (p=0.14). All intraepithelial neoplasia (IEN) detected contained low-grade dysplasia only. A total of 6751 non-targeted biopsies detected one IEN only. The withdrawal time was similar in both arms of the study; median of 24 min (HDWL) versus 25.5 min (HDV).ConclusionHDV and HDWL did not differ significantly in the detection of neoplasia. Almost all neoplasia were detected on targeted biopsy or resection. Quadrantic non-targeted biopsies have negligible additional gain.Trial registration numberClinical Trial.gov ID NCT02822352.
Published: 2020
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41. Determinants of Cardiovascular Risk in 7000 Youth With Type 1 Diabetes in the Australasian Diabetes Data Network

Author: Kim C Donaghue, Bruce R. King, D Jane Holmes-Walker, Craig Jefferies, Meng Tuck Mok, P Shane Hamblin, Melissa Chee, Timothy W. Jones, Helen L. Barrett, Elizabeth E Davis, Arul Earnest, Benjamin J Wheeler, Richard O. Sinnott, Stephanie R. Johnson, Anthony Zimmermann, Glenn M. Ward, Fergus J. Cameron, P. Gerry Fegan, Jenny Couper, Maria E. Craig, Philip Bergman, and Peter G. Colman
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Databases, Factual, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Overweight, Community Networks, Biochemistry, Body Mass Index, Young Adult, chemistry.chemical_compound, Endocrinology, Risk Factors, Interquartile range, Internal medicine, Diabetes mellitus, Humans, Medicine, Longitudinal Studies, Child, Creatinine, Type 1 diabetes, Australasia, business.industry, Cholesterol, Biochemistry (medical), Age Factors, medicine.disease, Diabetes Mellitus, Type 1, Blood pressure, chemistry, Cardiovascular Diseases, Heart Disease Risk Factors, Child, Preschool, Female, medicine.symptom, business, Body mass index, Diabetic Angiopathies
Abstract: Context Cardiovascular disease occurs prematurely in type 1 diabetes. The additional risk of overweight is not well characterized. Objective The primary aim was to measure the impact of body mass index (BMI) in youth with type 1 diabetes on cardiovascular risk factors. The secondary aim was to identify other determinants of cardiovascular risk. Design Observational longitudinal study of 7061 youth with type 1 diabetes followed for median 7.3 (interquartile range [IQR] 4-11) years over 41 (IQR 29-56) visits until March 2019. Setting 15 tertiary care diabetes centers in the Australasian Diabetes Data Network. Participants were aged 2 to 25 years at baseline, with at least 2 measurements of BMI and blood pressure. Main Outcome Measure Standardized systolic and diastolic blood pressure scores and non–high-density lipoprotein (HDL) cholesterol were co-primary outcomes. Urinary albumin/creatinine ratio was the secondary outcome. Results BMI z-score related independently to standardized blood pressure z- scores and non-HDL cholesterol. An increase in 1 BMI z-score related to an average increase in systolic/diastolic blood pressure of 3.8/1.4 mmHg and an increase in non-HDL cholesterol (coefficient + 0.16 mmol/L, 95% confidence interval [CI], 0.13-0.18; P Conclusions BMI had a modest independent effect on cardiovascular risk. Females and Indigenous Australians in particular had a more adverse risk profile.
Published: 2020
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42. The rise of metastatic bone disease in Ireland

Author: John P. McCabe, Dima Y. Jadaan, Fergus J. McCabe, and Mutaz M. Jadaan
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Bone disease, Population, Bone Neoplasms, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Surgical oncology, Internal medicine, Epidemiology, medicine, Humans, Registries, education, Aged, education.field_of_study, business.industry, Incidence, Incidence (epidemiology), Age Factors, Cancer, Bone metastasis, General Medicine, Middle Aged, medicine.disease, Cancer registry, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, Ireland
Abstract: To describe the expected rise of metastatic bone disease in Ireland, the relative primary types, and the locations of spread within the skeleton. This was a population-based epidemiological study using cancer registry data. We included patients with known metastatic cancer to bone, within 1 year of the primary diagnosis, during the years 1994 to 2012 inclusive. Our main outcome measures were age-specific, gender-specific and age-standardised incidence rates of bone metastasis, primary types and metastatic location within the skeleton. There were 14,495 recognised cases of bone metastasis in Ireland, 1994-2012 inclusive. Cases consistently rose over the time period, with 108% case increase and 51% age-standardised incidence rise. Annual percentage change increased across both genders and over all age groups. Most of this rise was not due to demographic population change. Breast, prostate and lung accounted for the majority of primary types. GI cancers were the fourth most common primary type. There were proportional increases in breast and lung, with proportional decreases in prostate. The spine was the major metastatic site. Bone metastasis is a significant and rising healthcare concern in Ireland. This rise is disproportionate to demographic changes. Breast, prostate and lung cancers account for the majority. GI cancers are implicated in an unexpectedly high number of cases. Spine is the most common location of bony metastasis, especially at presentation. Prudent healthcare planning is necessitated to prepare for the growing consequences of bone metastasis in cancer patients.
Published: 2020
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43. Has subsidized continuous glucose monitoring improved outcomes in pediatric diabetes?

Author: Susan Donath, Ella Ek Swaney, Julia McCombe, Fergus J. Cameron, Brenda Coggan, and Michele A O'Connell
Subjects: Blood Glucose, Male, Financing, Government, Pediatrics, medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Statistical analysis, In patient, 030212 general & internal medicine, Child, Glycated Hemoglobin, Type 1 diabetes, Tertiary Healthcare, Pediatric diabetes, business.industry, Continuous glucose monitoring, Blood Glucose Self-Monitoring, Australia, nutritional and metabolic diseases, medicine.disease, Hypoglycemia, Diabetes Mellitus, Type 1, Metabolic control analysis, Pediatrics, Perinatology and Child Health, Female, Observational study, Outcome data, business
Abstract: Introduction In 2017, the Australian Federal Government fully subsidized continuous glucose monitoring (CGM) devices for patients under 21 years of age with T1D with the aim of reducing rates of severe hypoglycaemia (SH) and improving metabolic control. The aim of this study was to reports on metabolic outcomes in youth from a single tertiary centre. Methods The study design was observational. Data were obtained on youth who commenced CGM between May 2017 and December 2019. Results Three hundred and forty one youth who commenced CGM and had clinical outcome data for a minimum of 4 months. 301, 261, 216, 172, and 125 had outcome data out to 8, 12, 16, 20, and 24 months, respectively. Cessation occurred between 27.9% and 32.8% of patients 12 to 24 months after CGM commencement. HbA1c did not change in patients who continued to use CGM. In the 12 months prior to starting CGM the rate of severe hypoglycaemia events were 5.0 per 100 patient years. The rates of severe hypoglycaemia in those continuing to use CGM at 4, 8, 12, 16, 20, and 24 months, were 5.2, 5.1, 1.6, 6.1, 2.4, and 0 per 100 patient years, respectively. Discussion Our experience of patients either ceasing or underusing CGM is less than reported in other cohorts but is nonetheless still high. There may have been a reduction in rates of severe hypoglycaemia over the 24 months follow up period; however, the absolute numbers of events were so low as to preclude meaningful statistical analysis.
Published: 2020
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44. Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Author: Andrew Neil, Kim C. Donaghue, Sally M. Marshall, Maria E. Craig, Jennifer J Couper, Paul M. McKeigue, Fergus J. Cameron, Denis Daneman, Timothy W. Jones, Paul Z. Benitez-Aguirre, Marco Colombo, Scott T Chiesa, Elizabeth A. Davis, Helen M. Colhoun, David B. Dunger, M. L. Marcovecchio, John E. Deanfield, Farid H. Mahmud, and Raymond Neil Dalton
Subjects: Adult, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Renal function, 030209 endocrinology & metabolism, Gastroenterology, Nephropathy, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Diabetic Nephropathies, 030212 general & internal medicine, Cystatin C, Child, Type 1 diabetes, biology, business.industry, Age Factors, Middle Aged, medicine.disease, Fibroblast Growth Factors, Fibroblast Growth Factor-23, Diabetes Mellitus, Type 1, Pediatrics, Perinatology and Child Health, biology.protein, Biomarker (medicine), Osteopontin, Microalbuminuria, Trefoil Factor-3, beta 2-Microglobulin, business, Biomarkers, Glomerular Filtration Rate
Abstract: OBJECTIVES: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D.METHODS: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes 3 mL/min/1.73m2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource.RESULTS: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR.CONCLUSIONS: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.
Published: 2020
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45. Hypoxia PET/CT and Colorectal Cancer: A Case Report

Author: Kirsten Laws, Graeme I Murray, Keith Kerr, Fergus McKiddie, Sergio Dall’Angelo, Matteo Zanda, Ian Fleming, and Leslie Samuel
Subjects: Oncology, medicine.medical_specialty, PET-CT, Lung, medicine.diagnostic_test, Colorectal cancer, business.industry, Pathological staging, medicine.medical_treatment, Disease, medicine.disease, medicine.anatomical_structure, Positron emission tomography, Internal medicine, medicine, Immunohistochemistry, Thoracotomy, business
Abstract: Introduction: Colorectal cancer risk stratification traditionally focuses on tumor node metastasis staging. Seemingly equivalent tumors can differ unpredictably in prognosis; more sophisticated quantification and stratification methods are required to identify tumors with a high likelihood of becoming metastatic. Hypoxia (low oxygen concentration) is associated with aggressive phenotypes and poor prognosis. Hypoxia is associated with treatment resistance consequently there is an unmet clinical requirement to develop personalised treatment based on hypoxia. Positron emission tomography/computed tomography (PET/CT) imaging can non-invasively detect hypoxic tumors. [18F]Fluoroazomycin arabinoside ([18F]FAZA) is a leading hypoxia PET/CT radiotracer, and uptake is associated with lower disease free survival. Case Report: A 78-year-old man, diagnosed with a localised colorectal cancer, underwent [18F]FAZA PET/CT imaging pre-operatively. This confirmed hypoxic regions in the tumor with correlation demonstrated with carbonic anhydrase IX (CAIX) immunohistochemistry (IHC). He underwent a right hemicolectomy. The pathological staging for his colorectal cancer predicted a good outcome; thus, he did not receive adjuvant chemotherapy. The patient subsequently developed early metastatic disease with two lung metastases, which were resected by thoracotomy and wedge resection. He continues on follow up at present with no evidence of recurrent disease. Conclusion: Hypoxia can be an important marker in colorectal cancer when determining risk and prognosis. We present evidence of clinical correlation of FAZA uptake and CAIX IHC in colorectal cancer, a key aspect in FAZA tracer validation. PET/CT potentially provides a specific tool for stratification for hypoxia-related treatment modification and development of hypoxia biomarkers.
Published: 2020
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46. Cilostazol for Secondary Prevention of Stroke and Cognitive Decline

Author: Francesca M Chappell, Joanna M. Wardlaw, Jason P. Appleton, Fergus N. Doubal, Philip M.W. Bath, Gordon W. Blair, and Caroline A. McHutchison
Subjects: medicine.medical_specialty, aspirin, Original Contributions, Phosphodiesterase 3, Phosphodiesterase 3 Inhibitors, Clinical and Population Sciences, Fibrinolytic Agents, Internal medicine, Secondary Prevention, Humans, Medicine, Cognitive Dysfunction, Cognitive decline, Stroke, Advanced and Specialized Nursing, Secondary prevention, Aspirin, clopidogrel, business.industry, stroke, lacunar, Clopidogrel, medicine.disease, stroke, Cilostazol, meta-analysis, Meta-analysis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, cilostazol, medicine.drug
Abstract: Supplemental Digital Content is available in the text., Background and Purpose: Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression. Methods: A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742). Results: We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57–0.81]; P6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance. Conclusions: Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease.
Published: 2020
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47. Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients – control survival is much better than previously assumed

Author: Tracy T. Batchelor, Norman R. Williams, Adrian Marchbank, Fergus Macbeth, Michael Shackcloth, Aman S. Coonar, Vern Farewell, D. Tsang, Tom Treasure, B. Davidson, Joel Dunning, Misel Milosevic, J. Hasan, S. Grumett, John G. Edwards, Farewell, Vernon [0000-0001-6704-5295], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, Lung Neoplasms, Randomization, lung metastasectomy, Colorectal cancer, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Stage (cooking), Lung cancer, Neoplasm Staging, Retrospective Studies, business.industry, Hazard ratio, Metastasectomy, Gastroenterology, medicine.disease, Survival Rate, 030220 oncology & carcinogenesis, randomized controlled trial, 030211 gastroenterology & hepatology, Observational study, Colorectal Neoplasms, business
Abstract: Aim\ud\udLung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial.\udMethod\ud\udMultidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis.\udResults\ud\udFrom 2010 to 2016, 93 participants were randomized. These patients were 35–86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1–6.6) years compared with 3.8 (95% CI: 3.1–4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56–1.56). Use of chemotherapy or local ablation was infrequent and similar in each group.\udConclusion\ud\udPatients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.
Published: 2020
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48. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA

Author: M.C. Liu, G.R. Oxnard, E.A. Klein, C. Swanton, M.V. Seiden, Minetta C. Liu, Geoffrey R. Oxnard, Eric A. Klein, David Smith, Donald Richards, Timothy J. Yeatman, Allen L. Cohn, Rosanna Lapham, Jessica Clement, Alexander S. Parker, Mohan K. Tummala, Kristi McIntyre, Mikkael A. Sekeres, Alan H. Bryce, Robert Siegel, Xuezhong Wang, David P. Cosgrove, Nadeem R. Abu-Rustum, Jonathan Trent, David D. Thiel, Carlos Becerra, Manish Agrawal, Lawrence E. Garbo, Jeffrey K. Giguere, Ross M. Michels, Ronald P. Harris, Stephen L. Richey, Timothy A. McCarthy, David M. Waterhouse, Fergus J. Couch, Sharon T. Wilks, Amy K. Krie, Rama Balaraman, Alvaro Restrepo, Michael W. Meshad, Kimberly Rieger-Christ, Travis Sullivan, Christine M. Lee, Daniel R. Greenwald, William Oh, Che-Kai Tsao, Neil Fleshner, Hagen F. Kennecke, Maged F. Khalil, David R. Spigel, Atisha P. Manhas, Brian K. Ulrich, Philip A. Kovoor, Christopher Stokoe, Jay G. Courtright, Habte A. Yimer, Timothy G. Larson, Charles Swanton, Michael V. Seiden, Steven R. Cummings, Farnaz Absalan, Gregory Alexander, Brian Allen, Hamed Amini, Alexander M. Aravanis, Siddhartha Bagaria, Leila Bazargan, John F. Beausang, Jennifer Berman, Craig Betts, Alexander Blocker, Joerg Bredno, Robert Calef, Gordon Cann, Jeremy Carter, Christopher Chang, Hemanshi Chawla, Xiaoji Chen, Tom C. Chien, Daniel Civello, Konstantin Davydov, Vasiliki Demas, Mohini Desai, Zhao Dong, Saniya Fayzullina, Alexander P. Fields, Darya Filippova, Peter Freese, Eric T. Fung, Sante Gnerre, Samuel Gross, Meredith Halks-Miller, Megan P. Hall, Anne-Renee Hartman, Chenlu Hou, Earl Hubbell, Nathan Hunkapiller, Karthik Jagadeesh, Arash Jamshidi, Roger Jiang, Byoungsok Jung, TaeHyung Kim, Richard D. Klausner, Kathryn N. Kurtzman, Mark Lee, Wendy Lin, Jafi Lipson, Hai Liu, Qinwen Liu, Margarita Lopatin, Tara Maddala, M. Cyrus Maher, Collin Melton, Andrea Mich, Shivani Nautiyal, Jonathan Newman, Joshua Newman, Virgil Nicula, Cosmos Nicolaou, Ongjen Nikolic, Wenying Pan, Shilpen Patel, Sarah A. Prins, Richard Rava, Neda Ronaghi, Onur Sakarya, Ravi Vijaya Satya, Jan Schellenberger, Eric Scott, Amy J. Sehnert, Rita Shaknovich, Avinash Shanmugam, K.C. Shashidhar, Ling Shen, Archana Shenoy, Seyedmehdi Shojaee, Pranav Singh, Kristan K. Steffen, Susan Tang, Jonathan M. Toung, Anton Valouev, Oliver Venn, Richard T. Williams, Tony Wu, Hui H. Xu, Christopher Yakym, Xiao Yang, Jessica Yecies, Alexander S. Yip, Jack Youngren, Jeanne Yue, Jingyang Zhang, Lily Zhang, Lori (Quan) Zhang, Nan Zhang, Christina Curtis, and Donald A. Berry
Subjects: 0301 basic medicine, medicine.medical_specialty, Bisulfite sequencing, Rectum, Gastroenterology, Article, cell-free DNA, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Positron Emission Tomography Computed Tomography, Internal medicine, Biomarkers, Tumor, medicine, cancer, Humans, Mass Screening, Prospective Studies, Esophagus, Early Detection of Cancer, business.industry, Stomach, DNA, Neoplasm, Hematology, DNA Methylation, Plasma cell neoplasm, 16. Peace & justice, Anus, Confidence interval, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cell-free fetal DNA, 030220 oncology & carcinogenesis, Feasibility Studies, Female, next-generation sequencing, methylation, business, Cell-Free Nucleic Acids
Abstract: Background Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. Participants and methods The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. Results Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. Conclusions cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.
Published: 2020
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49. Incidence of type 1 diabetes in 0 to 14 year olds in Australia from 2002 to 2017

Author: Fergus J. Cameron, Jennifer J Couper, Antony R Lafferty, Elizabeth A. Davis, Maria E. Craig, Karen Demangone, Stephanie R. Johnson, Phil Bergman, Angela Titmuss, Aveni Haynes, and Max Bulsara
Subjects: Male, Research design, Pediatrics, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Age at diagnosis, 030209 endocrinology & metabolism, History, 21st Century, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Incidence trends, Epidemiology, Internal Medicine, medicine, Humans, Registries, 030212 general & internal medicine, Age of Onset, Child, Type 1 diabetes, business.industry, Incidence, Incidence (epidemiology), Australia, Infant, Newborn, Infant, medicine.disease, Diabetes Mellitus, Type 1, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Age of onset, business
Abstract: To determine the incidence of childhood onset type 1 diabetes in Australia from 2002 to 2017, and analyze incidence rate trends by calendar year, sex, and age at diagnosis.Children newly diagnosed with type 1 diabetes aged15 years between 2002 and 2017 were identified from the National Diabetes Register, estimated to be ~99% complete. Data were obtained for diagnosis year, sex, age, and residential State/Territory at time of diagnosis. Population estimates by year, sex, single year of age, and State/Territory were obtained from the Australian Bureau of Statistics and Poisson regression used to examine incidence and trends by calendar year, sex, and age group at diagnosis.Between 2002 and 2017, there were 16 783 newly diagnosed cases of type 1 diabetes in children aged15 years (8684 boys: 8099 girls), giving a mean incidence of 25.0/1 00 000 person years (95%CI: 24.6, 25.4). A sinusoidal pattern in the incidence rate trend was observed with 5-yearly cycles providing the best model fit. No significant difference was observed in boys compared to girls (IRR 0.98 [95%CI: 0.95, 1.01]). Compared to 0 to 4 year olds, the mean incidence was 75% higher in 5 to 9 year olds, and 224% higher in 10 to 14 year olds. A decreasing incidence rate trend was observed in 0 to 4 year old boys and girls.This study reports updated incidence and incidence rate trends in children and adolescents diagnosed with type 1 diabetes in Australia. A cyclical pattern in incidence trend persists, with an overall decreasing trend observed only in the youngest age group.
Published: 2020
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50. Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women

Author: Loic LeMarchand, Esther M. John, Song Yao, Mia M. Gaudet, Chi Gao, Tuya Pal, Julie R. Palmer, Kimberly A. Bertrand, Payal D. Shah, Rohan Gnanaolivu, Katherine L. Nathanson, Chunling Hu, Susan M. Domchek, Peter Kraft, Jie Na, Leslie Bernstein, Fergus J. Couch, David E Goldgar, Eric C. Polley, Elisa V. Bandera, Dale P. Sandler, Christine B. Ambrosone, Jeffrey N. Weitzel, Amy Trentham-Dietz, Siddhartha Yadav, Steven N. Hart, William Yang, Kun Y. Lee, Christopher A. Haiman, Traci N. Bethea, Hongyan Huang, and Hoda Anton-Culver
Subjects: Oncology, 0303 health sciences, Cancer Research, medicine.medical_specialty, education.field_of_study, medicine.diagnostic_test, business.industry, PALB2, Population, Estrogen receptor, Cancer, Gene mutation, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, education, CHEK2, 030304 developmental biology, Genetic testing
Abstract: Background The risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies. Methods Germline DNA samples were sequenced for mutations in 23 cancer predisposition genes using a QIAseq multiplex amplicon panel. Prevalence of mutations and odds ratios (ORs) for associations with breast cancer risk were estimated with adjustment for study design, age, and family history of breast cancer. Results Pathogenic mutations were identified in 10.3% of women with estrogen receptor (ER)-negative breast cancer, 5.2% of women with ER-positive breast cancer, and 2.3% of unaffected women. Mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (OR = 47.55, 95% confidence interval [CI] = 10.43 to >100; OR = 7.25, 95% CI = 4.07 to 14.12; OR = 8.54, 95% CI = 3.67 to 24.95, respectively). RAD51D mutations were associated with high risk of ER-negative disease (OR = 7.82, 95% CI = 1.61 to 57.42). Moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer. Conclusions The study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.
Published: 2020
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