14 results on '"Mehenny, Susan"'
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2. Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors
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Kaptoge, Stephen, Di Angelantonio, Emanuele, Moore, Carmel, Walker, Matthew, Armitage, Jane, Ouwehand, Willem H, Roberts, David J, Danesh, John, Thompson, Simon G, Donovan, Jenny, Ford, Ian, Henry, Rachel, Hunt, Beverley J, le Huray, Bridget, Mehenny, Susan, Miflin, Gail, Green, Jane, Stredder, Mike, Watkins, Nicholas A, McDermott, Alan, Ronaldson, Clive, Thomson, Claire, Tolkien, Zoe, Williamson, Lorna, Allan, David, Sambrook, Jennifer, Hammerton, Tracey, Bruce, David, Choudry, Fizzah, Ghvaert, Cedric, Jonston, Kirstie, Kelly, Anne, King, Andrew, Mo, Alfred, Page, Lizanne, Richardson, Penny, Senior, Peter, Umrania, Yagnesh, Wong, Henna, Burchell, Brendan, Gallacher, John, Murphy, Gavin, Newland, Adrian C, Wheatley, Keith, Greaves, Michael, Turner, Marc, Aziz, Tahir, Brain, Richard, Davies, Christine, Turner, Ruth, Wakeman, Paula, Dent, Alison, Wakeman, Alan, Anthony, Ben, Bland, Desmond, Parrondo, Willem H, Vincent, Helen, Weatherill, Candy, Forsyth, Andrea, Butterfield, Carol, Wright, Tracey, Ellis, Karen, Johnston, Kristie, Poynton, Pat, Brooks, Carolyn, Martin, Emma, Littler, Lara, Williamson, Lindsay, Blair, Donna, Ackerley, Karen, Woods, Lynn, Stanley, Sophie, Walsh, Gemma, Franklin, Gayle, Howath, Cheryl, Sharpe, Sarah, Smith, Deborah, Botham, Lauren, Williams, Caroline, Alexander, Claire, Sowerbutts, Gareth, Furnival, Diane, Thake, Michael, Patel, Shilpa, Roost, Carolyn, Sowerby, Sandra, Appleton, Mary Joy, Bays, Eileen, Bowyer, Geoff, Clarkson, Steven, Halson, Stuart, Holmes, Kate, Humphreys, Gareth, Parvin-Cooper, Lee, Towler, Jason, Addy, Joanne, Barrass, Patrica, Stennett, Louise, Burton, Susan, Dingwell, Hannah, Clarke, Victoria, Potton, Maria, Bolton, Thomas, Daynes, Michael, Spackman, Sarah, Walker, Michael, Momodu, Abudu, Fenton, James, King, Adam, Muhammad, Omer, Oates, Nicholas, Peakman, Tim, Ryan, Christine, Spreckley, Kristian, Stubbins, Craig, Williams, Joanna, Brannan, James, Mochon, Cedric, Taylor, Samantha, Warren, Kimberly, and Mant, Jonathan
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- 2019
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3. Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors
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Di Angelantonio, Emanuele, Thompson, Simon G, Kaptoge, Stephen, Moore, Carmel, Walker, Matthew, Armitage, Jane, Ouwehand, Willem H, Roberts, David J, Danesh, John, Donovan, Jenny, Ford, Ian, Henry, Rachel, Hunt, Beverley J, Le Huray, Bridget, Mehenny, Susan, Miflin, Gail, Green, Jane, Stredder, Mike, Watkins, Nicholas A, McDermott, Alan, Ronaldson, Clive, Thomson, Claire, Tolkien, Zoe, Williamson, Lorna, Allen, David, Sambrook, Jennifer, Hammerton, Tracey, Bruce, David, Choudry, Fizzah, Ghevaert, Cedric, Johnston, Kirstie, Kelly, Anne, King, Andrew, Mo, Alfred, Page, Lizanne, Richardson, Penny, Senior, Peter, Umrania, Yagnesh, Wong, Henna, Murphy, Gavin, Newland, Adrian C, Wheatley, Keith, Greaves, Michael, Turner, Marc, Aziz, Tahir, Brain, Richard, Davies, Christine, Turner, Ruth, Wakeman, Paula, Dent, Alison, Wakeman, Alan, Anthony, Ben, Bland, Desmond, Parrondo, Will, Vincent, Helen, Weatherill, Candy, Forsyth, Andrea, Butterfield, Carol, Wright, Tracey, Ellis, Karen, Poynton, Pat, Brooks, Carolyn, Martin, Emma, Littler, Lara, Williams, Lindsay, Blair, Donna, Ackerley, Karen, Woods, Lynn, Stanley, Sophie, Walsh, Gemma, Franklin, Gayle, Howath, Cheryl, Sharpe, Sarah, Smith, Deborah, Botham, Lauren, Williams, Caroline, Alexander, Claire, Sowerbutts, Gareth, Furnival, Diane, Thake, Michael, Patel, Shilpa, Roost, Carolyn, Sowerby, Sandra, Appleton, Mary Joy, Bays, Eileen, Bowyer, Geoff, Clarkson, Steven, Halson, Stuart, Holmes, Kate, Humphries, Gareth, Parvin-Cooper, Lee, Towler, Jason, Addy, Joanne, Barrass, Patricia, Stennett, Louise, Burton, Susan, Dingwall, Hannah, Clarke, Victoria, Potton, Maria, Bolton, Thomas, Daynes, Michael, Spackman, Sarah, Momodu, Abudu, Fenton, James, King, Adam, Muhammed, Omer, Oates, Nicholas, Peakman, Tim, Ryan, Christine, Spreckley, Kristian, Stubbins, Craig, Williams, Joanna, Brennan, James, Mochon, Cedric, Taylor, Samantha, Warren, Kimberley, and Mant, Jonathan
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- 2017
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4. Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.
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McMahon, Amy, primary, Kaptoge, Stephen, additional, Walker, Matthew, additional, Mehenny, Susan, additional, Gilchrist, Philippe T, additional, Sambrook, Jennifer, additional, Akhtar, Naim, additional, Sweeting, Michael, additional, Wood, Angela M, additional, Stirrups, Kathleen, additional, Chung, Ryan, additional, Fahle, Sarah, additional, Johnson, Elisha, additional, Cullen, Donna, additional, Godfrey, Rosemary, additional, Duthie, Shannon, additional, Allen, Louise, additional, Harvey, Paul, additional, Berkson, Michael, additional, Allen, Elizabeth, additional, Watkins, Nicholas A, additional, Bradley, John R, additional, Kingston, Nathalie, additional, Miflin, Gail, additional, Armitage, Jane, additional, Roberts, David J, additional, Danesh, John, additional, and Angelantonio, Emanuele Di, additional
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- 2022
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5. Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study
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Bell, Steven, Sweeting, Michael, Ramond, Anna, Chung, Ryan, Kaptoge, Stephen, Walker, Matthew, Bolton, Thomas, Sambrook, Jennifer, Moore, Carmel, McMahon, Amy, Fahle, Sarah, Cullen, Donna, Mehenny, Susan, Wood, Angela M, Armitage, Jane, Ouwehand, Willem H, Miflin, Gail, Roberts, David J, Danesh, John, Di Angelantonio, Emanuele, COMPARE Study Group, Bell, Steven [0000-0001-6774-3149], Sweeting, Michael [0000-0003-0980-8965], Ramond, Anna [0000-0002-9958-3693], Fahle, Sarah [0000-0002-4359-9952], Wood, Angela M [0000-0002-7937-304X], Armitage, Jane [0000-0001-8691-9226], Ouwehand, Willem H [0000-0002-7744-1790], Di Angelantonio, Emanuele [0000-0001-8776-6719], and Apollo - University of Cambridge Repository
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Adult ,Male ,Adolescent ,haemoglobin screening ,Blood Donors ,gravimetry ,inappropriate bleeding ,Sensitivity and Specificity ,Donor Selection ,Hemoglobins ,Young Adult ,HemoCue ,Humans ,non-invasive haemoglobin measurement ,Aged ,Aged, 80 and over ,inappropriate deferral ,Cross-Over Studies ,Anemia ,Middle Aged ,Reference Standards ,Spectrophotometry ,whole blood donor ,Hemoglobinometry ,Female ,Biomarkers - Abstract
OBJECTIVE: To compare four haemoglobin measurement methods in whole blood donors. BACKGROUND: To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold). METHODS: We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) "post donation" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) "portable haemoglobinometry" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation ("deferred") incorrectly; and test preference. RESULTS: Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry. CONCLUSION: In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry.
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- 2021
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6. Accuracy of UK Rapid Test Consortium (UK-RTC) 'AbC-19 Rapid Test' for detection of previous SARS-CoV-2 infection in key workers: test accuracy study
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Mulchandani, Ranya, Jones, Hayley E, Taylor-Phillips, Sian, Shute, Justin, Perry, Keith, Jamarani, Shabnam, Brooks, Tim, Charlett, Andre, Hickman, Matthew, Oliver, Isabel, Kaptoge, Stephen, Danesh, John, Di Angelantonio, Emanuele, Ades, Anthony E, Wyllie, David H, Armitage, Jane, Borrow, Ray, Boyes, John, Cullen, Donna, Hormis, Anil, Linley, Ezra, Mehenny, Susan, Miflin, Gail, Moore, Carmel, Moore, Philippa, Reckless, Ian, Roberts, David J, Sambrook, Jennifer, and Todd, Neil
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Male ,medicine.medical_specialty ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Health Personnel ,Population ,Pneumonia, Viral ,serology ,030204 cardiovascular system & hematology ,Sensitivity and Specificity ,Serology ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,COVID-19 Testing ,Predictive Value of Tests ,Internal medicine ,False positive paradox ,medicine ,Humans ,030212 general & internal medicine ,education ,Pandemics ,Immunoassay ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Clinical Laboratory Techniques ,SARS-CoV-2 ,Research ,lateral flow immunoassay ,COVID-19 ,Covid19 ,General Medicine ,test accuracy ,Confidence interval ,Police ,United Kingdom ,Test (assessment) ,Predictive value of tests ,Firefighters ,Female ,Reagent Kits, Diagnostic ,business ,Coronavirus Infections - Abstract
Objective To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design Test accuracy study. Setting Laboratory based evaluation. Participants 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. Main outcome measures AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. Results Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). Conclusions AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to “spectrum bias.” Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. Study registration ISRCTN 56609224.
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- 2020
7. Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): a diagnostic accuracy study
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Bell, Steven, primary, Sweeting, Michael, additional, Ramond, Anna, additional, Chung, Ryan, additional, Kaptoge, Stephen, additional, Walker, Matthew, additional, Bolton, Thomas, additional, Sambrook, Jennifer, additional, Moore, Carmel, additional, McMahon, Amy, additional, Fahle, Sarah, additional, Cullen, Donna, additional, Mehenny, Susan, additional, Wood, Angela M, additional, Armitage, Jane, additional, Ouwehand, Willem H, additional, Miflin, Gail, additional, Roberts, Dave J, additional, Danesh, John, additional, and Angelantonio, Emanuele Di, additional
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- 2020
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8. Additional file 1: of Recruitment and representativeness of blood donors in the INTERVAL randomised trial assessing varying inter-donation intervals
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Moore, Carmel, Bolton, Thomas, Walker, Matthew, Kaptoge, Stephen, Allen, David, Daynes, Michael, Mehenny, Susan, Sambrook, Jennifer, Watkins, Nicholas A., Miflin, Gail, Angelantonio, Emanuele Di, Ouwehand, Willem, Roberts, David, Danesh, John, and Thompson, Simon
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INTERVAL trial â statistical analysis plan for principal paper. (PDF 74 kb)
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- 2016
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9. Recruitment and representativeness of blood donors in the INTERVAL randomised trial assessing varying inter-donation intervals
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Moore, Carmel, primary, Bolton, Thomas, additional, Walker, Matthew, additional, Kaptoge, Stephen, additional, Allen, David, additional, Daynes, Michael, additional, Mehenny, Susan, additional, Sambrook, Jennifer, additional, Watkins, Nicholas A., additional, Miflin, Gail, additional, Di Angelantonio, Emanuele, additional, Ouwehand, Willem H., additional, Roberts, David J., additional, Danesh, John, additional, and Thompson, Simon G., additional
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- 2016
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10. The INTERVAL trial to determine whether intervals between blood donations can be safely and acceptably decreased to optimise blood supply: study protocol for a randomised controlled trial
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Moore, Carmel, primary, Sambrook, Jennifer, additional, Walker, Matthew, additional, Tolkien, Zoe, additional, Kaptoge, Stephen, additional, Allen, David, additional, Mehenny, Susan, additional, Mant, Jonathan, additional, Angelantonio, Emanuele Di, additional, Thompson, Simon G, additional, Ouwehand, Willem, additional, Roberts, David J, additional, and Danesh, John, additional
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- 2014
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11. Recruitment and representativeness of blood donors in the INTERVAL randomised trial assessing varying inter-donation intervals
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Moore, Carmel, Bolton, Thomas, Walker, Matthew, Kaptoge, Stephen, Allen, David, Daynes, Michael, Mehenny, Susan, Sambrook, Jennifer, Watkins, Nicholas A, Miflin, Gail, Di Angelantonio, Emanuele, Ouwehand, Willem H, Roberts, David J, Danesh, John, Thompson, Simon G, Kaptoge, Stephen [0000-0002-1155-4872], Di Angelantonio, Emanuele [0000-0001-8776-6719], Ouwehand, Willem [0000-0002-7744-1790], Danesh, John [0000-0003-1158-6791], Thompson, Simon [0000-0002-5274-7814], and Apollo - University of Cambridge Repository
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Adult ,Male ,Blood donation ,Randomised trial ,Generalisability ,Time Factors ,Adolescent ,Research ,Health Status ,Patient Selection ,Medicine (miscellaneous) ,Blood Donors ,Middle Aged ,Donor Selection ,Young Adult ,England ,Blood Banks ,Humans ,Female ,Pharmacology (medical) ,Recruitment ,Representativeness ,Aged - Abstract
Background The interpretation of trial results can be helped by understanding how generalisable they are to the target population for which inferences are intended. INTERVAL, a large pragmatic randomised trial of blood donors in England, is assessing the effectiveness and safety of reducing inter-donation intervals. The trial recruited mainly from the blood service’s static centres, which collect only about 10 % of whole-blood donations. Hence, the extent to which the trial’s participants are representative of the general blood donor population is uncertain. We compare these groups in detail. Methods We present the CONSORT flowchart from participant invitation to randomisation in INTERVAL. We compare the characteristics of those eligible and consenting to participate in INTERVAL with the general donor population, using the national blood supply ’PULSE’ database for the period of recruitment. We compare the characteristics of specific groups of trial participants recruited from different sources, as well as those who were randomised versus those not randomised. Results From a total of 540,459 invitations, 48,725 donors were eligible and consented to participate in INTERVAL. The proportion of such donors varied from 1–22 % depending on the source of recruitment. The characteristics of those consenting were similar to those of the general population of 1.3 million donors in terms of ethnicity, blood group distribution and recent deferral rates from blood donation due to low haemoglobin. However, INTERVAL participants included more men (50 % versus 44 %), were slightly older (mean age 43.1 versus 42.3 years), included fewer new donors (3 % versus 22 %) and had given more donations over the previous 2 years (mean 3.3 versus 2.2) than the general donor population. Of the consenting participants, 45,263 (93 %) donors were randomised. Compared to those not randomised, the randomised donors showed qualitatively similar differences to those described above. Conclusions There was broad similarity of participants in INTERVAL with the general blood donor population of England, notwithstanding some differences in age, sex and donation history. Any heterogeneity of the trial’s results according to these characteristics will need to be studied to ensure its generalisability to the general donor population. Trial registration Current Controlled Trials ISRCTN24760606. Registered on 25 January 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1579-7) contains supplementary material, which is available to authorized users.
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12. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
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Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M., Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K., Barakat, Farah, Auth, Marcus K. H., Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P., Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C., Gilmour, Kimberly C., Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A., Fulga, Tudor A., Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C., Elkadri, Abdul, Griffiths, Anne M., Snapper, Scott B., Shah, Neil, Muise, Aleixo M., Wilson, David C., Uhlig, Holm H., Anderson, Carl A., Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Arancibia-Carcamo, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Elizabeth Louise, Brain, Oliver, Braden, Barbara, Collier, Jane, East, James, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Powrie, Fiona, Simmons, Alison, Walker, Matthew, Tolkien, Zoe, Kaptoge, Stephen, Allen, David, Mehenny, Susan, Mant, Jonathan, Di Angelantonio, Emanuele, Thompson, Simon G., Yilmaz, Bahtiyar, Juillerat, Pascal, Geuking, Markus, Wiest, Reiner, Macpherson, Andrew J., Bravo, Francisco Damian, Brügger, Lukas, Carstens, Ove, Bigler, Ulrike Graf, Heimgartner, Benjamin, Rusticeanu, Monica, Schmid (-Uebelhart), Sybille, Strebel, Bruno, Tatu, Aurora, Tutuian, Radu, Øyås, Ove, Ramon, Charlotte, Stelling, Jörg, Franc, Yannick, Fournier, Nicolas, Pittet, Valerie E. H., Burnand, Bernard, Egger, Mara, Golay, Delphine, Marot, Astrid, Musso, Leilla, Pittet, Valérie, Rossel, Jean-Benoît, Seematter, Vivianne, Sommer, Joachim, Vulliamy, Rachel, Michetti, Pierre, Maillard, Michel H., Keller, Céline, Nydegger, Andreas, Schoepfe, Alain, Archanioti, Eva, Ezri, Jessica, Fraga, Montserrat, Schoepfer, Alain, Müller, Christoph, Rogler, Gerhard, Biedermann, Luc, Blattmann, Mirjam, Burk, Sabine, Dora, Barbara, Fried, Michael, Misselwitz, Benjamin, Müllhaupt, Beat, Obialo, Nicole, Pohl, Daniel, Raschle, Nadia, Scharl, Michael, Vavricka, Stephan, Von Känel, Roland, Zeitz, Jonas, Abdelrahman, Karim, Ademi, Gentiana, Borovicka, Jan, Brand, Stephan, Frei, Remus, Haarer, Johannes, Knellwolf (-Grieger), Christina, Krieger(-Grübel), Claudia, Künzler, Patrizia, Meyenberger, Christa, Meyer, Pamela, Röhrich, Nina, Sawatzki, Mikael, Schelling, Martin, Semadeni, Gian-Marco, Sulz, Michael, Zimmermann, Dorothee, Aepli, Patrick, Criblez, Dominique H., Hess, Cyrill, Richterich, Jean-Pierre, Spalinger, Johannes, Staudenmann, Dominic, Stulz, Andreas, Wöhrle, Stefanie, Thomas, Amman, Anderegg, Claudia, Köhler, Henrik, Kusche, Rachel, Antonino, Anca-Teodora, Arrigoni, Eviano, Bengoa, José M., Cunningham, Sophie, De Saussure, Philippe, Girard, Laurent, De Jong, Diana Bakker, Bastürk, Polat, Brunner, Simon, Degen, Lukas, Hruz, Petr, Bakker, Carolina Khalid-De, Niess, Jan, Balsiger, Bruno, Haldemann, Janine, Saner, Gaby, Seibold, Frank, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Binek, Janek, Hengstler, Peter, Boehm, Stephan, Boldanov, Tujana, Bühr, Patrick, Koller, Rebekka, Rueger, Vanessa, Senning, Arne, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, D’Angelo, Fabrizia, Delarive, Joakim, Doerig, Christopher, Hessler, Roxane, Preissler, Claudia, Rentsch, Ronald, Risti, Branislav, Ritz, Marc Alain, Steuerwald, Michael, Vögtlin, Jürg, Sagmeister, Markus, Sauter, Bernhard, Schibli, Susanne, Sokollik, Christiane, Schlauri, Hugo, Schnegg, Jean-François, Seirafi, Mariam, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Stenz, Volker, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Urfer, Patrick, Viani, Francesco, Vouillamoz, Dominique, Zander, Silvan, Wyli, Tina, Jostins, L., Kennedy, N. A., Ahmad, T., Lamb, C. A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Mathew, C. G., Lees, C. W., McGovern, D. P. B., Targan, S. R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J. D., Bitton, A., Côté-Daigneault, J., Daly, M. J., Xavier, R., Morris, K., Boucher, G., Cho, J. H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R. H., Konnikova, L., Schwartz, M. B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S. R., Datta, L., Silverberg, M. S., Schumm, L. P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., and Haritunians, T.
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49/31 ,45 ,article ,45/22 ,631/208/1516 ,692/699/249/1570 ,45/23 ,631/250/249/2510/257 ,631/208/248 ,13 ,digestive system diseases ,3. Good health ,49 - Abstract
Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.
13. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
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Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, Marlen, Zurek, Caterina, Strisciuglio, Mamoun, Elawad, Bernice, Lo, Carolina, Arancibia-Carcamo, Adam, Bailey, Ellie, Barnes, Elizabeth Louise, Bird-Lieberman, Oliver, Brain, Barbara, Braden, Jane, Collier, James, East, Lucy, Howarth, Satish, Keshav, Paul, Klenerman, Simon, Leedham, Rebecca, Palmer, Fiona, Powrie, Alison, Simmons, Matthew, Walker, Zoe, Tolkien, Stephen, Kaptoge, David, Allen, Susan, Mehenny, Jonathan, Mant, Emanuele, Di Angelantonio, Simon G, Thompson, Bahtiyar, Yilmaz, Pascal, Juillerat, Markus, Geuking, Reiner, Wiest, Andrew J, Macpherson, Francisco Damian, Bravo, Lukas, Brügger, Ove, Carstens, Ulrike Graf, Bigler, Benjamin, Heimgartner, Monica, Rusticeanu, Sybille, Schmid-Uebelhart, Bruno, Strebel, Aurora, Tatu, Radu, Tutuian, Ove, Øyås, Charlotte, Ramon, Jörg, Stelling, Yannick, Franc, Nicolas, Fournier, Valerie E H, Pittet, Bernard, Burnand, Mara, Egger, Delphine, Golay, Astrid, Marot, Leilla, Musso, Valérie, Pittet, Jean-Benoît, Rossel, Vivianne, Seematter, Joachim, Sommer, Rachel, Vulliamy, Pierre, Michetti, Michel H, Maillard, Céline, Keller, Andreas, Nydegger, Alain, Schoepfe, Eva, Archanioti, Jessica, Ezri, Montserrat, Fraga, Alain, Schoepfer, Christoph, Müller, Gerhard, Rogler, Luc, Biedermann, Mirjam, Blattmann, Sabine, Burk, Barbara, Dora, Michael, Fried, Benjamin, Misselwitz, Beat, Müllhaupt, Nicole, Obialo, Daniel, Pohl, Nadia, Raschle, Michael, Scharl, Stephan, Vavricka, Roland, Von Känel, Jonas, Zeitz, Karim, Abdelrahman, Gentiana, Ademi, Jan, Borovicka, Stephan, Brand, Remus, Frei, Johannes, Haarer, Christina, Knellwolf-Grieger, Claudia, Krieger-Grübel, Patrizia, Künzler, Christa, Meyenberger, Pamela, Meyer, Nina, Röhrich, Mikael, Sawatzki, Martin, Schelling, Gian-Marco, Semadeni, Michael, Sulz, Dorothee, Zimmermann, Patrick, Aepli, Dominique H, Criblez, Cyrill, Hess, Jean-Pierre, Richterich, Johannes, Spalinger, Dominic, Staudenmann, Andreas, Stulz, Stefanie, Wöhrle, Amman, Thomas, Claudia, Anderegg, Henrik, Köhler, Rachel, Kusche, Anca-Teodora, Antonino, Eviano, Arrigoni, José M, Bengoa, Sophie, Cunningham, Philippe, de Saussure, Laurent, Girard, Diana Bakker, de Jong, Polat, Bastürk, Simon, Brunner, Lukas, Degen, Petr, Hruz, Carolina, Khalid-de Bakker, Jan, Niess, Bruno, Balsiger, Janine, Haldemann, Gaby, Saner, Frank, Seibold, Peter, Bauerfeind, Andrea, Becocci, Dominique, Belli, Janek, Binek, Peter, Hengstler, Stephan, Boehm, Tujana, Boldanov, Patrick, Bühr, Rebekka, Koller, Vanessa, Rueger, Arne, Senning, Emanuel, Burri, Sophie, Buyse, Dahlia-Thao, Cao, Fabrizia, D'Angelo, Joakim, Delarive, Christopher, Doerig, Roxane, Hessler, Claudia, Preissler, Ronald, Rentsch, Branislav, Risti, Marc Alain, Ritz, Michael, Steuerwald, Jürg, Vögtlin, Markus, Sagmeister, Bernhard, Sauter, Susanne, Schibli, Christiane, Sokollik, Hugo, Schlauri, Jean-François, Schnegg, Mariam, Seirafi, Holger, Spangenberger, Philippe, Stadler, Peter, Staub, Volker, Stenz, Michela, Tempia-Caliera, Joël, Thorens, Kaspar, Truninger, Patrick, Urfer, Francesco, Viani, Dominique, Vouillamoz, Silvan, Zander, Tina, Wyli, L, Jostins, N A, Kennedy, T, Ahmad, C A, Lamb, C, Edwards, A, Hart, C, Hawkey, J C, Mansfield, C, Mowat, W G, Newman, A, Simmons, M, Tremelling, J C, Lee, N J, Prescott, C G, Mathew, C W, Lees, D P B, McGovern, S R, Targan, G, Botwin, E, Mengesha, P, Fleshner, C, Landers, D, Li, J D, Rioux, A, Bitton, J, Côté-Daigneault, M J, Daly, R, Xavier, K, Morris, G, Boucher, J H, Cho, C, Abraham, M, Merad, B, Sands, I, Peter, K, Hao, Y, Itan, R H, Duerr, L, Konnikova, M B, Schwartz, S, Proksell, E, Johnston, V, Miladinova, W, Chen, S R, Brant, L, Datta, M S, Silverberg, L P, Schumm, S, Birch, M, Giri, K, Gettler, Y, Sharma, C, Stevens, M, Lazarev, T, Haritunians, Fachal, Laura [0000-0002-7256-9752], Croft, Nicholas M [0000-0002-1519-6435], Posovszky, Carsten [0000-0002-9487-8812], Russell, Richard K [0000-0001-7398-4926], Zilbauer, Matthias [0000-0002-7272-0547], Travis, Simon P [0000-0002-2690-4361], Matte, Julie C [0000-0001-5642-648X], Wedrychowicz, Andrzej [0000-0003-1448-167X], Fulga, Tudor A [0000-0002-1056-0082], Karaminejadranjbar, Mohammad [0000-0002-7770-2065], Ahmed, Ahmed [0000-0001-6509-2581], Muise, Aleixo M [0000-0001-9624-3346], Wilson, David C [0000-0003-0879-1129], Apollo - University of Cambridge Repository, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Croft, Nicholas M. [0000-0002-1519-6435], Russell, Richard K. [0000-0001-7398-4926], Travis, Simon P. [0000-0002-2690-4361], Matte, Julie C. [0000-0001-5642-648X], Fulga, Tudor A. [0000-0002-1056-0082], Muise, Aleixo M. [0000-0001-9624-3346], Wilson, David C. [0000-0003-0879-1129], Eva Gonçalves, Serra, Tobias, Schwerd, Loukas, Moutsiana, Athena, Cavounidi, Laura, Fachal, Sumeet, Pandey, Jochen, Kammermeier, Nicholas M, Croft, Carsten, Posovszky, Astor, Rodrigue, Richard K, Russell, Farah, Barakat, Marcus K H, Auth, Robert, Heuschkel, Matthias, Zilbauer, Krzysztof, Fyderek, Christian, Braegger, Simon P, Travi, Jack, Satsangi, Miles, Parke, Nikhil, Thapar, Helen, Ferry, Julie C, Matte, Kimberly C, Gilmour, Andrzej, Wedrychowicz, Peter, Sullivan, Carmel, Moore, Jennifer, Sambrook, Willem, Ouwehand, David, Robert, John, Danesh, Toni A, Baeumler, Tudor A, Fulga, Mohammad, Karaminejadranjbar, Ahmed, Ahmed, Rachel, Wilson, Jeffrey C, Barrett, Abdul, Elkadri, Anne M, Griffith, Scott B, Snapper, Neil, Shah, Aleixo M, Muise, David C, Wilson, Holm H, Uhlig, Carl A, Anderson, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Arancibia-Carcamo, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Elizabeth Louise, Brain, Oliver, Braden, Barbara, Collier, Jane, East, Jame, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Powrie, Fiona, Simmons, Alison, Walker, Matthew, Tolkien, Zoe, Kaptoge, Stephen, Allen, David, Mehenny, Susan, Mant, Jonathan, Di Angelantonio, Emanuele, Thompson, Simon G, Yilmaz, Bahtiyar, Juillerat, Pascal, Geuking, Marku, Wiest, Reiner, Macpherson, Andrew J, Bravo, Francisco Damian, Brügger, Luka, Carstens, Ove, Bigler, Ulrike Graf, Heimgartner, Benjamin, Rusticeanu, Monica, Schmid-Uebelhart, Sybille, Strebel, Bruno, Tatu, Aurora, Tutuian, Radu, Øyås, Ove, Ramon, Charlotte, Stelling, Jörg, Franc, Yannick, Fournier, Nicola, Pittet, Valerie E H, Burnand, Bernard, Egger, Mara, Golay, Delphine, Marot, Astrid, Musso, Leilla, Pittet, Valérie, Rossel, Jean-Benoît, Seematter, Vivianne, Sommer, Joachim, Vulliamy, Rachel, Michetti, Pierre, Maillard, Michel H, Keller, Céline, Nydegger, Andrea, Schoepfe, Alain, Archanioti, Eva, Ezri, Jessica, Fraga, Montserrat, Schoepfer, Alain, Müller, Christoph, Rogler, Gerhard, Biedermann, Luc, Blattmann, Mirjam, Burk, Sabine, Dora, Barbara, Fried, Michael, Misselwitz, Benjamin, Müllhaupt, Beat, Obialo, Nicole, Pohl, Daniel, Raschle, Nadia, Scharl, Michael, Vavricka, Stephan, Von Känel, Roland, Zeitz, Jona, Abdelrahman, Karim, Ademi, Gentiana, Borovicka, Jan, Brand, Stephan, Frei, Remu, Haarer, Johanne, Knellwolf-Grieger, Christina, Krieger-Grübel, Claudia, Künzler, Patrizia, Meyenberger, Christa, Meyer, Pamela, Röhrich, Nina, Sawatzki, Mikael, Schelling, Martin, Semadeni, Gian-Marco, Sulz, Michael, Zimmermann, Dorothee, Aepli, Patrick, Criblez, Dominique H, Hess, Cyrill, Richterich, Jean-Pierre, Spalinger, Johanne, Staudenmann, Dominic, Stulz, Andrea, Wöhrle, Stefanie, Thomas, Amman, Anderegg, Claudia, Köhler, Henrik, Kusche, Rachel, Antonino, Anca-Teodora, Arrigoni, Eviano, Bengoa, José M, Cunningham, Sophie, de Saussure, Philippe, Girard, Laurent, de Jong, Diana Bakker, Bastürk, Polat, Brunner, Simon, Degen, Luka, Hruz, Petr, Khalid-de Bakker, Carolina, Niess, Jan, Balsiger, Bruno, Haldemann, Janine, Saner, Gaby, Seibold, Frank, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Binek, Janek, Hengstler, Peter, Boehm, Stephan, Boldanov, Tujana, Bühr, Patrick, Koller, Rebekka, Rueger, Vanessa, Senning, Arne, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, D'Angelo, Fabrizia, Delarive, Joakim, Doerig, Christopher, Hessler, Roxane, Preissler, Claudia, Rentsch, Ronald, Risti, Branislav, Ritz, Marc Alain, Steuerwald, Michael, Vögtlin, Jürg, Sagmeister, Marku, Sauter, Bernhard, Schibli, Susanne, Sokollik, Christiane, Schlauri, Hugo, Schnegg, Jean-Françoi, Seirafi, Mariam, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Stenz, Volker, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Urfer, Patrick, Viani, Francesco, Vouillamoz, Dominique, Zander, Silvan, Wyli, Tina, Jostins, L, Kennedy, N A, Ahmad, T, Lamb, C A, Edwards, C, Hart, A, Hawkey, C, Mansfield, J C, Mowat, C, Newman, W G, Simmons, A, Tremelling, M, Lee, J C, Prescott, N J, Mathew, C G, Lees, C W, Mcgovern, D P B, Targan, S R, Botwin, G, Mengesha, E, Fleshner, P, Landers, C, Li, D, Rioux, J D, Bitton, A, Côté-Daigneault, J, Daly, M J, Xavier, R, Morris, K, Boucher, G, Cho, J H, Abraham, C, Merad, M, Sands, B, Peter, I, Hao, K, Itan, Y, Duerr, R H, Konnikova, L, Schwartz, M B, Proksell, S, Johnston, E, Miladinova, V, Chen, W, Brant, S R, Datta, L, Silverberg, M S, Schumm, L P, Birch, S, Giri, M, Gettler, K, Sharma, Y, Stevens, C, Lazarev, M, Haritunians, T, Carrami, Eli M [0000-0002-7770-2065], COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, Zurek, M., Strisciuglio, C., Elawad, M., Lo, B., Arancibia-Carcamo, C., Bailey, A., Barnes, E., Bird-Lieberman, E.L., Brain, O., Braden, B., Collier, J., East, J., Howarth, L., Keshav, S., Klenerman, P., Leedham, S., Palmer, R., Powrie, F., Simmons, A., Walker, M., Tolkien, Z., Kaptoge, S., Allen, D., Mehenny, S., Mant, J., Di Angelantonio, E., Thompson, S.G., Yilmaz, B., Juillerat, P., Geuking, M., Wiest, R., Macpherson, A.J., Bravo, F.D., Brügger, L., Carstens, O., Bigler, U.G., Heimgartner, B., Rusticeanu, M., Schmid-Uebelhart, S., Strebel, B., Tatu, A., Tutuian, R., Øyås, O., Ramon, C., Stelling, J., Franc, Y., Fournier, N., Pittet, VEH, Burnand, B., Egger, M., Golay, D., Marot, A., Musso, L., Pittet, V., Rossel, J.B., Seematter, V., Sommer, J., Vulliamy, R., Michetti, P., Maillard, M.H., Keller, C., Nydegger, A., Schoepfe, A., Archanioti, E., Ezri, J., Fraga, M., Schoepfer, A., Müller, C., Rogler, G., Biedermann, L., Blattmann, M., Burk, S., Dora, B., Fried, M., Misselwitz, B., Müllhaupt, B., Obialo, N., Pohl, D., Raschle, N., Scharl, M., Vavricka, S., Von Känel, R., Zeitz, J., Abdelrahman, K., Ademi, G., Borovicka, J., Brand, S., Frei, R., Haarer, J., Knellwolf-Grieger, C., Krieger-Grübel, C., Künzler, P., Meyenberger, C., Meyer, P., Röhrich, N., Sawatzki, M., Schelling, M., Semadeni, G.M., Sulz, M., Zimmermann, D., Aepli, P., Criblez, D.H., Hess, C., Richterich, J.P., Spalinger, J., Staudenmann, D., Stulz, A., Wöhrle, S., Thomas, A., Anderegg, C., Köhler, H., Kusche, R., Antonino, A.T., Arrigoni, E., Bengoa, J.M., Cunningham, S., de Saussure, P., Girard, L., de Jong, D.B., Bastürk, P., Brunner, S., Degen, L., Hruz, P., Bakker, C.K., Niess, J., Balsiger, B., Haldemann, J., Saner, G., Seibold, F., Bauerfeind, P., Becocci, A., Belli, D., Binek, J., Hengstler, P., Boehm, S., Boldanov, T., Bühr, P., Koller, R., Rueger, V., Senning, A., Burri, E., Buyse, S., Cao, D.T., D'Angelo, F., Delarive, J., Doerig, C., Hessler, R., Preissler, C., Rentsch, R., Risti, B., Ritz, M.A., Steuerwald, M., Vögtlin, J., Sagmeister, M., Sauter, B., Schibli, S., Sokollik, C., Schlauri, H., Schnegg, J.F., Seirafi, M., Spangenberger, H., Stadler, P., Staub, P., Stenz, V., Tempia-Caliera, M., Thorens, J., Truninger, K., Urfer, P., Viani, F., Vouillamoz, D., Zander, S., Wyli, T., Jostins, L., Kennedy, N.A., Ahmad, T., Lamb, C.A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J.C., Mowat, C., Newman, W.G., Tremelling, M., Lee, J.C., Prescott, N.J., Mathew, C.G., Lees, C.W., McGovern, DPB, Targan, S.R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J.D., Bitton, A., Côté-Daigneault, J., Daly, M.J., Xavier, R., Morris, K., Boucher, G., Cho, J.H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R.H., Konnikova, L., Schwartz, M.B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S.R., Datta, L., Silverberg, M.S., Schumm, L.P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., and Haritunians, T.
- Subjects
0301 basic medicine ,Male ,Multifactorial Inheritance ,General Physics and Astronomy ,631/208/1516 ,13 ,Inflammatory bowel disease ,Whole Exome Sequencing ,Adult ,Age of Onset ,Case-Control Studies ,Child ,Child, Preschool ,Cohort Studies ,Female ,Genes, Recessive ,Genetic Predisposition to Disease ,Genetic Variation ,Humans ,Infant ,Infant, Newborn ,Inflammatory Bowel Diseases/etiology ,Inflammatory Bowel Diseases/genetics ,Loss of Function Mutation ,Mosaicism ,Mutation ,NADPH Oxidase 2/genetics ,Pedigree ,Primary Immunodeficiency Diseases/complications ,Primary Immunodeficiency Diseases/genetics ,Risk Factors ,0302 clinical medicine ,Primary Immunodeficiency Disease ,Medicine ,lcsh:Science ,Exome sequencing ,49/31 ,education.field_of_study ,Multidisciplinary ,Medical genetics ,article ,692/699/249/1570 ,631/250/249/2510/257 ,631/208/248 ,3. Good health ,NADPH Oxidase 2 ,030211 gastroenterology & hepatology ,Case-Control Studie ,Human ,medicine.medical_specialty ,Science ,Primary Immunodeficiency Diseases ,Population ,45/22 ,45/23 ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immunological deficiency syndromes ,Exome Sequencing ,Immunogenetics ,Allele ,education ,45 ,business.industry ,Risk Factor ,Inflammatory Bowel Disease ,Case-control study ,General Chemistry ,medicine.disease ,Inflammatory Bowel Diseases ,digestive system diseases ,49 ,030104 developmental biology ,Immunology ,Primary immunodeficiency ,lcsh:Q ,Age of onset ,Cohort Studie ,business - Abstract
Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P, Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.
- Published
- 2020
14. Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.
- Author
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Bell S, Sweeting M, Ramond A, Chung R, Kaptoge S, Walker M, Bolton T, Sambrook J, Moore C, McMahon A, Fahle S, Cullen D, Mehenny S, Wood AM, Armitage J, Ouwehand WH, Miflin G, Roberts DJ, Danesh J, and Di Angelantonio E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Anemia blood, Biomarkers analysis, Biomarkers blood, Cross-Over Studies, Donor Selection standards, Female, Hemoglobinometry standards, Hemoglobins metabolism, Humans, Male, Middle Aged, Reference Standards, Sensitivity and Specificity, Spectrophotometry, Young Adult, Anemia diagnosis, Blood Donors, Donor Selection methods, Hemoglobinometry methods, Hemoglobins analysis
- Abstract
Objective: To compare four haemoglobin measurement methods in whole blood donors., Background: To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold)., Methods: We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) "post donation" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) "portable haemoglobinometry" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation ("deferred") incorrectly; and test preference., Results: Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry., Conclusion: In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry., (© 2020 The Authors. Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)
- Published
- 2021
- Full Text
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