128 results on '"Davies, Melanie J"'
Search Results
2. Translating trial results into interpretable risk estimates: Systematic analysis of cardiorenal outcome trials of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.
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Rizzi, Alessandro, Kloecker, David E., Pitocco, Dario, Khunti, Kamlesh, Davies, Melanie J., and Zaccardi, Francesco
- Abstract
In a randomised controlled trial (RCT), the between-arm difference in the average probability of an event per unit of time (i.e., yearly incidence risk difference, YIRD) is an easy-to-interpret treatment effect metric. We aimed to quantify the YIRD in cardiorenal RCTs of GLP-1RAs or SGLT-2is. We digitally searched for RCTs published up to March 1st, 2023, including subjects with type 2 diabetes randomised to GLP-1RAs or SGLT-2is and investigating cardiorenal outcomes or death. We extracted information from Kaplan-Meier (KM) plots to obtain time-to-event individual data and estimate within-arm yearly incidence risk and YIRD. Data from 19 RCTs (28 kM plots) were analysed: comparing treatment to placebo, in GLP-1RA RCTs the YIRD ranged from 0.2 % (95 % CI: −0.7 %, 1.1 %) to −1.9 % (−3.1, −0.7), for primary outcome; and from −0.2 % (−0.5, 0.2) to −0.4 % (−0.7 %, −0.0 %), for mortality. With the exception of SOLOIST-WHF (YIRD 11.9 % for primary outcome), corresponding estimates in SGLT-2is RCTs were: from −0.1 % (−0.4, 0.1) to −5.0 % (−7.7, −2.6), for primary outcome; and from −0.1 % (−0.2, 0.1) to −1.9 % (−4.4 %, 0.6 %), for mortality. The YIRD metric complements other relative treatment effect estimates and helps quantify the absolute benefit of GLP-1RAs and SGLT-2is. • Yearly incidence risk difference (YIRD) can help interpreting treatment effect. • Using reconstructed time-to-event data, we estimated YIRD in cardiorenal trials. • YIRDs was estimated for primary outcomes and death in GLP1-RAs and SGLT2-is trials. • YIRD is easy-to-interpret and could add insights in clinical decision-making. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials
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Butler, Javed, Shah, Sanjiv J, Petrie, Mark C, Borlaug, Barry A, Abildstrøm, Steen Z, Davies, Melanie J, Hovingh, G Kees, Kitzman, Dalane W, Møller, Daniél Vega, Verma, Subodh, Einfeldt, Mette Nygaard, Lindegaard, Marie L, Rasmussen, Søren, Abhayaratna, Walter, Ahmed, Fozia Z, Ben-Gal, Tuvia, Chopra, Vijay, Ezekowitz, Justin A, Fu, Michael, Ito, Hiroshi, Lelonek, Małgorzata, Melenovský, Vojtěch, Merkely, Bela, Núñez, Julio, Perna, Eduardo, Schou, Morten, Senni, Michele, Sharma, Kavita, van der Meer, Peter, Von Lewinski, Dirk, Wolf, Dennis, and Kosiborod, Mikhail N
- Abstract
In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups.
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- 2024
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4. Self-reported walking pace and 10-year cause-specific mortality: A UK biobank investigation.
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Goldney, Jonathan, Dempsey, Paddy C., Henson, Joseph, Rowlands, Alex, Bhattacharjee, Atanu, Chudasama, Yogini V., Razieh, Cameron, Laukkanen, Jari A., Davies, Melanie J., Khunti, Kamlesh, Yates, Thomas, and Zaccardi, Francesco
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To investigate associations of self-reported walking pace (SRWP) with relative and absolute risks of cause-specific mortality. In 391,652 UK Biobank participants recruited in 2006–2010, we estimated sex- and cause-specific (cardiovascular disease [CVD], cancer, other causes) mortality hazard ratios (HRs) and 10-year mortality risks across categories of SRWP (slow, average, brisk), accounting for confounders and competing risk. Censoring occurred in September 30, 2021 (England, Wales) and October 31, 2021 (Scotland). Over a median follow-up of 12.6 years, 22,413 deaths occurred. In women, the HRs comparing brisk to slow SRWP were 0.74 (95% CI: 0.67, 0.82), 0.40 (0.33, 0.49), and 0.29 (0.26, 0.32) for cancer, CVD, and other causes of death, respectively, and 0.71 (0.64, 0.78), 0.38 (0.33, 0.44), and 0.29 (0.26, 0.32) in men. Compared to CVD, HRs were greater for other causes (women: 39.6% [6.2, 72.9]; men: 31.6% [9.8, 53.5]) and smaller for cancer (−45.8% [−58.3, −33.2] and − 45.9% [−54.8, −36.9], respectively). For all causes in both sexes, the 10-year mortality risk was higher in slow walkers, but varied across sex, age, and cause, resulting in different risk reductions comparing brisk to slow: the largest were for other causes of death at age 75 years [women: −6.8% (−7.7, −5.8); men: −9.5% (−10.6, −8.4)]. Compared to slow walkers, brisk SRWP was associated with reduced cancer (smallest reduction), CVD, and other (largest) causes of death and may therefore be a useful clinical predictive marker. As absolute risk reductions varied across age, cause, and SRWP, certain groups may particularly benefit from interventions to increase SRWP. [ABSTRACT FROM AUTHOR]
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- 2023
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5. A big STEP for treatment of heart failure with preserved ejection fraction.
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Verma, Subodh, Borlaug, Barry A., Butler, Javed, Davies, Melanie J., Kitzman, Dalane W., Petrie, Mark C., Shah, Sanjiv J., Dhingra, Nitish K., and Kosiborod, Mikhail N.
- Abstract
In the STEP-HFpEF trial, 2.4 mg semaglutide produced marked improvements in heart failure-related symptoms, physical limitations, and exercise function, and reduced inflammation and body weight in individuals with obesity HFpEF phenotype. These data usher in a new paradigm of targeting obesity as a therapeutic strategy in HFpEF. [ABSTRACT FROM AUTHOR]
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- 2023
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6. 210 - Once-weekly semaglutide in heart failure with preserved ejection fraction and obesity: main results from the STEP-HFpEF trial.
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Sindone, Andrew, Kosiborod, Mikhail, Abildstrøm, Steen Z, Borlaug, Barry A, Butler, Javed, Rasmussen, Søren, Davies, Melanie J, Hovingh, G. Kees, Kitzman, Dalane W, Lindegaard, Marie L, Møller, Daniél Vega, Shah, Sanjiv J, Treppendahl, Marianne Bach, Verma, Subodh, and Petrie, Mark C
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- 2024
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7. Implementation of a diabetes prevention programme in a multi-ethnic community in primary care in England: An evaluation using constructs from the RE-AIM Framework.
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Dallosso, Helen, Khunti, Kamlesh, Gray, Laura J., Hulley, Kerry, Ghaly, Mel, Patel, Naina, Kai, Joe, Aujla, Navneet, Davies, Melanie J., and Yates, Tom
- Abstract
To implement a diabetes prevention programme in primary care The programme was implemented for 12 months in two neighbouring towns, served by eight general practices. Practices requested a referral pathway involving an external administrator running electronic searches and sending postal invitations. If interested, people called and booked a place on the programme. Practices were also provided with resources to refer people directly. Six Educators were trained to deliver the programme. The RE-AIM constructs "Adoption", "Reach" and "Uptake" were assessed. All practices engaged in the searches and postal invitations. Overall, 3.9 % of those aged ≥ 25 years had an HbA1c level indicative of non-diabetic hyperglycaemia (NDH) and were invited. Overall uptake (attended as percentage of invited) was 16 % (practice range 10.5–26.6 %) and was highest in two practices where the invitation was followed by a telephone call. Four people were referred directly by their practice. Groups at risk of being excluded were the Bengali population and those unable to attend because of issues such as health, mobility and frailty. Comprehensive electronic searches meant everyone previously diagnosed with NDH was invited to attend. Follow-up telephone call improved uptake and providing practices with resources to make these calls themselves would likely increase uptake further. • General practices supported to implement diabetes prevention programme. • Practices requested support from external referral pathway. • 3.9 % of ≥ 25 y had HbA1c indicative of non-diabetic hyperglycaemia. • 16 % uptake to postal invitation, increased if followed by phone call. • Closer involvement by health care professionals likely to improve uptake. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Life expectancy following a cardiovascular event in individuals with and without type 2 diabetes: A UK multi-ethnic population-based observational study.
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Chudasama, Yogini V., Khunti, Kamlesh, Coles, Briana, Gillies, Clare L., Islam, Nazrul, Rowlands, Alex V., Seidu, Samuel, Razieh, Cameron, Davies, Melanie J., Samani, Nilesh J., Yates, Thomas, and Zaccardi, Francesco
- Abstract
We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; −1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group. Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups. • Limited evidence for the prognosis of individuals with cardiovascular disease (CVD) by type 2 diabetes (T2D) and ethnicity. • After first CVD, the largest life expectancy difference was in White ethnicity, (loss of 3.9 years) with vs without T2D. • Differences were non-significant in other ethnicity (3.9 years), Black (1.2 y), South Asian (-1.4 y) with vs without T2D. • Study shows the heterogeneous impact of T2D on life expectancy among individuals of different ethnicity who survived a CVD. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
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Raman, Betty, McCracken, Celeste, Cassar, Mark P, Moss, Alastair J, Finnigan, Lucy, Samat, Azlan Helmy A, Ogbole, Godwin, Tunnicliffe, Elizabeth M, Alfaro-Almagro, Fidel, Menke, Ricarda, Xie, Cheng, Gleeson, Fergus, Lukaschuk, Elena, Lamlum, Hanan, McGlynn, Kevin, Popescu, Iulia A, Sanders, Zeena-Britt, Saunders, Laura C, Piechnik, Stefan K, Ferreira, Vanessa M, Nikolaidou, Chrysovalantou, Rahman, Najib M, Ho, Ling-Pei, Harris, Victoria C, Shikotra, Aarti, Singapuri, Amisha, Pfeffer, Paul, Manisty, Charlotte, Kon, Onn M, Beggs, Mark, O'Regan, Declan P, Fuld, Jonathan, Weir-McCall, Jonathan R, Parekh, Dhruv, Steeds, Rick, Poinasamy, Krisnah, Cuthbertson, Dan J, Kemp, Graham J, Semple, Malcolm G, Horsley, Alexander, Miller, Christopher A, O'Brien, Caitlin, Shah, Ajay M, Chiribiri, Amedeo, Leavy, Olivia C, Richardson, Matthew, Elneima, Omer, McAuley, Hamish J C, Sereno, Marco, Saunders, Ruth M, Houchen-Wolloff, Linzy, Greening, Neil J, Bolton, Charlotte E, Brown, Jeremy S, Choudhury, Gourab, Diar Bakerly, Nawar, Easom, Nicholas, Echevarria, Carlos, Marks, Michael, Hurst, John R, Jones, Mark G, Wootton, Daniel G, Chalder, Trudie, Davies, Melanie J, De Soyza, Anthony, Geddes, John R, Greenhalf, William, Howard, Luke S, Jacob, Joseph, Man, William D-C, Openshaw, Peter J M, Porter, Joanna C, Rowland, Matthew J, Scott, Janet T, Singh, Sally J, Thomas, David C, Toshner, Mark, Lewis, Keir E, Heaney, Liam G, Harrison, Ewen M, Kerr, Steven, Docherty, Annemarie B, Lone, Nazir I, Quint, Jennifer, Sheikh, Aziz, Zheng, Bang, Jenkins, R Gisli, Cox, Eleanor, Francis, Susan, Halling-Brown, Mark, Chalmers, James D, Greenwood, John P, Plein, Sven, Hughes, Paul J C, Thompson, A A Roger, Rowland-Jones, Sarah L, Wild, James M, Kelly, Matthew, Treibel, Thomas A, Bandula, Steven, Aul, Raminder, Miller, Karla, Jezzard, Peter, Smith, Stephen, Nichols, Thomas E, McCann, Gerry P, Evans, Rachael A, Wain, Louise V, Brightling, Christopher E, Neubauer, Stefan, Baillie, J K, Shaw, Alison, Hairsine, Brigid, Kurasz, Claire, Henson, Helen, Armstrong, Lisa, Shenton, Liz, Dobson, H, Dell, Amanda, Lucey, Alice, Price, Andrea, Storrie, Andrew, Pennington, Chris, Price, Claire, Mallison, Georgia, Willis, Gemma, Nassa, Heeah, Haworth, Jill, Hoare, Michaela, Hawkings, Nancy, Fairbairn, Sara, Young, Susan, Walker, S, Jarrold, I, Sanderson, Amy, David, C, Chong-James, K, Zongo, O, James, W Y, Martineau, A, King, Bernie, Armour, C, McAulay, D, Major, E, McGinness, Jade, McGarvey, L, Magee, N, Stone, Roisin, Drain, S, Craig, T, Bolger, A, Haggar, Ahmed, Lloyd, Arwel, Subbe, Christian, Menzies, Daniel, Southern, David, McIvor, Emma, Roberts, K, Manley, R, Whitehead, Victoria, Saxon, W, Bularga, A, Mills, N L, El-Taweel, Hosni, Dawson, Joy, Robinson, Leanne, Saralaya, Dinesh, Regan, Karen, Storton, Kim, Brear, Lucy, Amoils, S, Bermperi, Areti, Elmer, Anne, Ribeiro, Carla, Cruz, Isabel, Taylor, Jessica, Worsley, J, Dempsey, K, Watson, L, Jose, Sherly, Marciniak, S, Parkes, M, McQueen, Alison, Oliver, Catherine, Williams, Jenny, Paradowski, Kerry, Broad, Lauren, Knibbs, Lucy, Haynes, Matthew, Sabit, Ramsey, Milligan, L, Sampson, Claire, Hancock, Alyson, Evenden, Cerys, Lynch, Ceri, Hancock, Kia, Roche, Lisa, Rees, Meryl, Stroud, Natalie, Thomas-Woods, T, Heller, S, Robertson, E, Young, B, Wassall, Helen, Babores, M, Holland, Maureen, Keenan, Natalie, Shashaa, Sharlene, Price, Carly, Beranova, Eva, Ramos, Hazel, Weston, Heather, Deery, Joanne, Austin, Liam, Solly, Reanne, Turney, Sharon, Cosier, Tracey, Hazelton, Tracy, Ralser, M, Wilson, Ann, Pearce, Lorraine, Pugmire, S, Stoker, Wendy, McCormick, W, Dewar, A, Arbane, Gill, Kaltsakas, G, Kerslake, Helen, Rossdale, J, Bisnauthsing, Karen, Aguilar Jimenez, Laura A, Martinez, L M, Ostermann, Marlies, Magtoto, Murphy M, Hart, Nicholas, Marino, Philip, Betts, Sarah, Solano, Teresa S, Arias, Ava Maria, Prabhu, A, Reed, Annabel, Wrey Brown, Caroline, Griffin, Denise, Bevan, Emily, Martin, Jane, Owen, J, Alvarez Corral, Maria, Williams, Nick, Payne, Sheila, Storrar, Will, Layton, Alison, Lawson, Cathy, Mills, Clare, Featherstone, James, Stephenson, Lorraine, Burdett, Tracy, Ellis, Y, Richards, A, Wright, C, Sykes, D L, Brindle, K, Drury, Katie, Holdsworth, L, Crooks, M G, Atkin, Paul, Flockton, Rachel, Thackray-Nocera, Susannah, Mohamed, Abdelrahman, Taylor, Abigail, Perkins, Emma, Ross, Gavin, McGuinness, Heather, Tench, Helen, Phipps, Janet, Loosley, Ronda, Wolf-Roberts, Rebecca, Coetzee, S, Omar, Zohra, Ross, Alexandra, Card, Bethany, Carr, Caitlin, King, Clara, Wood, Chloe, Copeland, D, Calvelo, Ellen, Chilvers, Edwin R, Russell, Emily, Gordon, Hussain, Nunag, Jose Lloyd, Schronce, J, March, Katherine, Samuel, Katherine, Burden, L, Evison, Lynsey, McLeavey, Laura, Orriss-Dib, Lorna, Tarusan, Lawrence, Mariveles, Myril, Roy, Maura, Mohamed, Noura, Simpson, Neil, Yasmin, Najira, Cullinan, P, Daly, Patrick, Haq, Sulaimaan, Moriera, Silvia, Fayzan, Tamanah, Munawar, Unber, Nwanguma, Uchechi, Lingford-Hughes, A, Altmann, Danny, Johnston, D, Mitchell, J, Valabhji, J, Price, L, Molyneaux, P L, Thwaites, Ryan S, Walsh, S, Frankel, A, Lightstone, L, Wilkins, M, Willicombe, M, McAdoo, S, Touyz, R, Guerdette, Anne-Marie, Warwick, Katie, Hewitt, Melanie, Reddy, R, White, Sonia, McMahon, A, Hoare, Amy, Knighton, Abigail, Ramos, Albert, Te, Amelie, Jolley, Caroline J, Speranza, Fabio, Assefa-Kebede, Hosanna, Peralta, Ida, Breeze, Jonathon, Shevket, K, Powell, Natassia, Adeyemi, Oluwaseun, Dulawan, Pearl, Adrego, Rita, Byrne, S, Patale, Sheetal, Hayday, A, Malim, M, Pariante, C, Sharpe, C, Whitney, J, Bramham, K, Ismail, K, Wessely, S, Nicholson, T, Ashworth, Andrew, Humphries, Amy, Tan, Ai Lyn, Whittam, Beverley, Coupland, C, Favager, Clair, Peckham, D, Wade, Elaine, Saalmink, Gwen, Clarke, Jude, Glossop, Jodie, Murira, Jennifer, Rangeley, Jade, Woods, Janet, Hall, Lucy, Dalton, Matthhew, Window, Nicola, Beirne, Paul, Hardy, Tim, Coakley, G, Turtle, Lance, Berridge, Anthony, Cross, Andy, Key, Angela L, Rowe, Anna, Allt, Ann Marie, Mears, Chloe, Malein, Flora, Madzamba, Gladys, Hardwick, H E, Earley, Joanne, Hawkes, Jenny, Pratt, James, Wyles, J, Tripp, K A, Hainey, Kera, Allerton, Lisa, Lavelle-Langham, L, Melling, Lucy, Wajero, Lilian O, Poll, L, Noonan, Matthew J, French, N, Lewis-Burke, N, Williams-Howard, S A, Cooper, Shirley, Kaprowska, Sabina, Dobson, S L, Marsh, Sophie, Highett, Victoria, Shaw, V, Beadsworth, M, Defres, S, Watson, Ekaterina, Tiongson, Gerlynn F, Papineni, Padmasayee, Gurram, Sambasivarao, Diwanji, Shalin N, Quaid, Sheena, Briggs, A, Hastie, Claire, Rogers, Natalie, Stensel, D, Bishop, L, McIvor, K, Rivera-Ortega, P, Al-Sheklly, B, Avram, Cristina, Faluyi, David, Blaikely, J, Piper Hanley, K, Radhakrishnan, K, Buch, M, Hanley, N A, Odell, Natasha, Osbourne, Rebecca, Stockdale, Sue, Felton, T, Gorsuch, T, Hussell, T, Kausar, Zunaira, Kabir, T, McAllister-Williams, H, Paddick, S, Burn, D, Ayoub, A, Greenhalgh, Alan, Sayer, A, Young, A, Price, D, Burns, G, MacGowan, G, Fisher, Helen, Tedd, H, Simpson, J, Jiwa, Kasim, Witham, M, Hogarth, Philip, West, Sophie, Wright, S, McMahon, Michael J, Neill, Paula, Dougherty, Andrew, Morrow, A, Anderson, David, Grieve, D, Bayes, Hannah, Fallon, K, Mangion, K, Gilmour, L, Basu, N, Sykes, R, Berry, C, McInnes, I B, Donaldson, A, Sage, E K, Barrett, Fiona, Welsh, B, Bell, Murdina, Quigley, Jackie, Leitch, Karen, Macliver, L, Patel, Manish, Hamil, R, Deans, Andrew, Furniss, J, Clohisey, S, Elliott, Anne, Solstice, A R, Deas, C, Tee, Caroline, Connell, David, Sutherland, Debbie, George, J, Mohammed, S, Bunker, Jenny, Holmes, Katie, Dipper, A, Morley, Anna, Arnold, David, Adamali, H, Welch, H, Morrison, Leigh, Stadon, Louise, Maskell, Nick, Barratt, Shaney, Dunn, Sarah, Waterson, Samuel, Jayaraman, Bhagy, Light, Tessa, Selby, N, Hosseini, A, Shaw, Karen, Almeida, Paula, Needham, Robert, Thomas, Andrew K, Matthews, Laura, Gupta, Ayushman, Nikolaidis, Athanasios, Dupont, Catherine, Bonnington, J, Chrystal, Melanie, Greenhaff, P L, Linford, S, Prosper, Sabrina, Jang, W, Alamoudi, Asma, Bloss, Angela, Megson, Clare, Nicoll, Debby, Fraser, Emily, Pacpaco, Edmund, Conneh, Florence, Ogg, G, McShane, H, Koychev, Ivan, Chen, Jin, Pimm, John, Ainsworth, Mark, Pavlides, M, Sharpe, M, Havinden-Williams, May, Petousi, Nayia, Talbot, Nick, Carter, Penny, Kurupati, Prathiba, Dong, T, Peng, Yanchun, Burns, A, Kanellakis, N, Korszun, A, Connolly, B, Busby, J, Peto, T, Patel, B, Nolan, C M, Cristiano, Daniele, Walsh, J A, Liyanage, Kamal, Gummadi, Mahitha, Dormand, N, Polgar, Oliver, George, P, Barker, R E, Patel, Suhani, Price, L, Gibbons, M, Matila, Darwin, Jarvis, Hannah, Lim, Lai, Olaosebikan, Olaoluwa, Ahmad, Shanaz, Brill, Simon, Mandal, S, Laing, C, Michael, Alice, Reddy, A, Johnson, C, Baxendale, H, Parfrey, H, Mackie, J, Newman, J, Pack, Jamie, Parmar, J, Paques, K, Garner, Lucie, Harvey, Alice, Summersgill, C, Holgate, D, Hardy, E, Oxton, J, Pendlebury, Jessica, McMorrow, L, Mairs, N, Majeed, N, Dark, P, Ugwuoke, R, Knight, Sean, Whittaker, S, Strong-Sheldrake, Sophia, Matimba-Mupaya, Wadzanai, Chowienczyk, P, Pattenadk, Dibya, Hurditch, E, Chan, Flora, Carborn, H, Foot, H, Bagshaw, J, Hockridge, J, Sidebottom, J, Lee, Ju Hee, Birchall, K, Turner, Kim, Haslam, L, Holt, L, Milner, L, Begum, M, Marshall, M, Steele, N, Tinker, N, Ravencroft, Phillip, Butcher, Robyn, Misra, S, Walker, S, Coburn, Zach, Fairman, Alexandra, Ford, Amber, Holbourn, Ailsa, Howell, Alice, Lawrie, Allan, Lye, Alison, Mbuyisa, Angeline, Zawia, Amira, Holroyd-Hind, B, Thamu, B, Clark, Cameron, Jarman, Claire, Norman, C, Roddis, C, Foote, David, Lee, Elvina, Ilyas, F, Stephens, G, Newell, Helen, Turton, Helena, Macharia, Irene, Wilson, Imogen, Cole, Joby, McNeill, J, Meiring, J, Rodger, J, Watson, James, Chapman, Kerry, Harrington, Kate, Chetham, Luke, Hesselden, L, Nwafor, Lorenza, Dixon, Myles, Plowright, Megan, Wade, Phillip, Gregory, Rebecca, Lenagh, Rebecca, Stimpson, R, Megson, Sharon, Newman, Tom, Cheng, Yutung, Goodwin, Camelia, Heeley, Cheryl, Sissons, D, Sowter, D, Gregory, Heidi, Wynter, Inez, Hutchinson, John, Kirk, Jill, Bennett, Kaytie, Slack, Katie, Allsop, Lynne, Holloway, Leah, Flynn, Margaret, Gill, Mandy, Greatorex, M, Holmes, Megan, Buckley, Phil, Shelton, Sarah, Turner, Sarah, Sewell, Terri Ann, Whitworth, V, Lovegrove, Wayne, Tomlinson, Johanne, Warburton, Louise, Painter, Sharon, Vickers, Carinna, Redwood, Dawn, Tilley, Jo, Palmer, Sue, Wainwright, Tania, Breen, G, Hotopf, M, Dunleavy, A, Teixeira, J, Ali, Mariam, Mencias, Mark, Msimanga, N, Siddique, Sulman, Samakomva, T, Tavoukjian, Vera, Forton, D, Ahmed, R, Cook, Amanda, Thaivalappil, Favas, Connor, Lynda, Rees, Tabitha, McNarry, M, Williams, N, McCormick, Jacqueline, McIntosh, Jerome, Vere, Joanne, Coulding, Martina, Kilroy, Susan, Turner, Victoria, Butt, Al-Tahoor, Savill, Heather, Fraile, Eva, Ugoji, Jacinta, Landers, G, Lota, Harpreet, Portukhay, Sofiya, Nasseri, Mariam, Daniels, Alison, Hormis, Anil, Ingham, Julie, Zeidan, Lisa, Osborne, Lynn, Chablani, Manish, Banerjee, A, David, A, Pakzad, A, Rangelov, B, Williams, B, Denneny, E, Willoughby, J, Xu, M, Mehta, P, Batterham, R, Bell, R, Aslani, S, Lilaonitkul, W, Checkley, A, Bang, Dongchun, Basire, Donna, Lomas, D, Wall, E, Plant, Hannah, Roy, K, Heightman, M, Lipman, M, Merida Morillas, Marta, Ahwireng, Nyarko, Chambers, R C, Jastrub, Roman, Logan, S, Hillman, T, Botkai, A, Casey, A, Neal, A, Newton-Cox, A, Cooper, B, Atkin, C, McGee, C, Welch, C, Wilson, D, Sapey, E, Qureshi, H, Hazeldine, J, Lord, J M, Nyaboko, J, Short, J, Stockley, J, Dasgin, J, Draxlbauer, K, Isaacs, K, Mcgee, K, Yip, K P, Ratcliffe, L, Bates, M, Ventura, M, Ahmad Haider, N, Gautam, N, Baggott, R, Holden, S, Madathil, S, Walder, S, Yasmin, S, Hiwot, T, Jackson, T, Soulsby, T, Kamwa, V, Peterkin, Z, Suleiman, Z, Chaudhuri, N, Wheeler, H, Djukanovic, R, Samuel, R, Sass, T, Wallis, T, Marshall, B, Childs, C, Marouzet, E, Harvey, M, Fletcher, S, Dickens, C, Beckett, P, Nanda, U, Daynes, E, Charalambou, A, Yousuf, A J, Lea, A, Prickett, A, Gooptu, Bibek, Hargadon, Beverley, Bourne, Charlotte, Christie, C, Edwardson, C, Lee, D, Baldry, E, Stringer, E, Woodhead, F, Mills, G, Arnold, H, Aung, H, Qureshi, I N, Finch, J, Skeemer, J, Hadley, K, Khunti, Kamlesh, Carr, Liesel, Ingram, L, Aljaroof, M, Bakali, M, Bakau, M, Baldwin, M, Bourne, Michelle, Pareek, Manish, Soares, M, Tobin, Martin, Armstrong, Natalie, Brunskill, Nigel, Goodman, N, Cairns, P, Haldar, Pranab, McCourt, P, Dowling, R, Russell, Richard, Diver, Sarah, Edwards, Sarah, Glover, Sarah, Parker, S, Siddiqui, Salman, Ward, T J C, Mcnally, T, Thornton, T, Yates, Tom, Ibrahim, W, Monteiro, Will, Thickett, D, Wilkinson, D, Broome, M, McArdle, P, Upthegrove, R, Wraith, D, Langenberg, C, Summers, C, Bullmore, E, Heeney, J L, Schwaeble, W, Sudlow, C L, Adeloye, D, Newby, D E, Rudan, I, Shankar-Hari, M, Thorpe, M, Pius, R, Walmsley, S, McGovern, A, Ballard, C, Allan, L, Dennis, J, Cavanagh, J, Petrie, J, O'Donnell, K, Spears, M, Sattar, N, MacDonald, S, Guthrie, E, Henderson, M, Guillen Guio, Beatriz, Zhao, Bang, Lawson, C, Overton, Charlotte, Taylor, Chris, Tong, C, Mukaetova-Ladinska, Elizabeta, Turner, E, Pearl, John E, Sargant, J, Wormleighton, J, Bingham, Michelle, Sharma, M, Steiner, Mike, Samani, Nilesh, Novotny, Petr, Free, Rob, Allen, R J, Finney, Selina, Terry, Sarah, Brugha, Terry, Plekhanova, Tatiana, McArdle, A, Vinson, B, Spencer, L G, Reynolds, W, Ashworth, M, Deakin, B, Chinoy, H, Abel, K, Harvie, M, Stanel, S, Rostron, A, Coleman, C, Baguley, D, Hufton, E, Khan, F, Hall, I, Stewart, I, Fabbri, L, Wright, L, Kitterick, P, Morriss, R, Johnson, S, Bates, A, Antoniades, C, Clark, D, Bhui, K, Channon, K M, Motohashi, K, Sigfrid, L, Husain, M, Webster, M, Fu, X, Li, X, Kingham, L, Klenerman, P, Miiler, K, Carson, G, Simons, G, Huneke, N, Calder, P C, Baldwin, D, Bain, S, Lasserson, D, Daines, L, Bright, E, Stern, M, Crisp, P, Dharmagunawardena, R, Reddington, A, Wight, A, Bailey, L, Ashish, A, Robinson, E, Cooper, J, Broadley, A, Turnbull, A, Brookes, C, Sarginson, C, Ionita, D, Redfearn, H, Elliott, K, Barman, L, Griffiths, L, Guy, Z, Gill, Rhyan, Nathu, Rashmita, Harris, Edward, Moss, P, Finnigan, J, Saunders, Kathryn, Saunders, Peter, Kon, S, Kon, Samantha S, O'Brien, Linda, Shah, K, Shah, P, Richardson, Emma, Brown, V, Brown, M, Brown, Jo, Brown, J, Brown, Ammani, Brown, Angela, Brown, M, Choudhury, N, Jones, S, Jones, H, Jones, L, Jones, I, Jones, G, Jones, Heather, Jones, Don, Davies, Ffyon, Davies, Ellie, Davies, Kim, Davies, Gareth, Davies, Gwyneth A, Howard, K, Porter, Julie, Rowland, J, Rowland, A, Scott, Kathryn, Singh, Suver, Singh, Claire, Thomas, S, Thomas, Caradog, Lewis, Victoria, Lewis, J, Lewis, D, Harrison, P, Francis, C, Francis, R, Hughes, Rachel Ann, Hughes, Joan, Hughes, A D, Thompson, T, Kelly, S, Smith, D, Smith, Nikki, Smith, Andrew, Smith, Jacqui, Smith, Laurie, Smith, Susan, Evans, Teriann, Evans, Ranuromanana I, Evans, D, Evans, R, Evans, H, and Evans, J
- Abstract
The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.
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- 2023
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10. 211 - Once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes: main results from the STEP-HFpEF DM trial.
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Sindone, Andrew, Kosiborod, Mikhail, Petrie, Mark C, Borlaug, Barry A, Butler, Javed, Davies, Melanie J, Hovingh, G. Kees, Kitzman, Dalane W, Møller, Daniél Vega, Treppendahl, Marianne Bach, Verma, Subodh, Jensen, Thomas J, Liisberg, Karoline, Lindegaard, Marie L, and Shah, Sanjiv J
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- 2024
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11. Differences in the risk of cardiovascular disease across ethnic groups: UK Biobank observational study.
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Razieh, Cameron, Zaccardi, Francesco, Miksza, Joanne, Davies, Melanie J, Hansell, Anna L, Khunti, Kamlesh, and Yates, Thomas
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Background and Aims: To describe sociodemographic, lifestyle, environmental and traditional clinical risk factor differences between ethnic groups and to investigate the extent to which such differences confound the association between ethnic groups and the risk of cardiovascular disease (CVD) METHODS AND RESULTS: A total of 440,693 white European (55.9% women), 7305 South Asian (48.6%) and 7628 black African or Caribbean (57.7%) people were included from UK Biobank. Associations between ethnicity and cardiovascular outcomes (composite of non-fatal stroke, non-fatal myocardial infarction and CVD death) were explored using Cox-proportional hazard models. Models were adjusted for sociodemographic, lifestyle, environmental and clinical risk factors. Over a median (IQR) of 12.6 (11.8, 13.3) follow-up years, there were 22,711 (5.15%) cardiovascular events in white European, 463 (6.34%) in South Asian and 302 (3.96%) in black African or Caribbean individuals. For South Asian people, the cardiovascular hazard ratio (HR) compared to white European people was 1.28 (99% CI [1.16, 1.43]). For black African or Caribbean people, the HR was 0.80 (0.66, 0.97). The elevated risk of CVD in South Asians remained after adjusting for differences in sociodemographic, lifestyle, environmental and clinical factors, whereas the lower risk in black African or Caribbean was largely attenuated.Conclusions: South Asian, but not black African or Caribbean individuals, have a higher risk of CVD compared to white European individuals. This higher risk in South Asians was independent of sociodemographic, lifestyle, environmental and clinical factors. [ABSTRACT FROM AUTHOR]- Published
- 2022
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12. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial
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Borlaug, Barry A., Kitzman, Dalane W., Davies, Melanie J., Rasmussen, Søren, Barros, Eric, Butler, Javed, Einfeldt, Mette Nygaard, Hovingh, G. Kees, Møller, Daniél Vega, Petrie, Mark C., Shah, Sanjiv J., Verma, Subodh, Abhayaratna, Walter, Ahmed, Fozia Z., Chopra, Vijay, Ezekowitz, Justin, Fu, Michael, Ito, Hiroshi, Lelonek, Małgorzata, Melenovsky, Vojtech, Núñez, Julio, Perna, Eduardo, Schou, Morten, Senni, Michele, van der Meer, Peter, Von Lewinski, Dirk, Wolf, Dennis, and Kosiborod, Mikhail N.
- Abstract
In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and exercise function and reduced body weight in patients with obesity phenotype of heart failure and preserved ejection fraction (HFpEF). This prespecified analysis examined the effects of semaglutide on dual primary endpoints (change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body weight) and confirmatory secondary endpoints (change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP)) across obesity classes I–III (body mass index (BMI) 30.0–34.9 kg m−2, 35.0–39.9 kg m−2and ≥40 kg m−2) and according to body weight reduction with semaglutide after 52 weeks. Semaglutide consistently improved all outcomes across obesity categories (Pvalue for treatment effects × BMI interactions = not significant for all). In semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater with larger body weight reduction (for example, 6.4-point (95% confidence interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS and 6MWD for each 10% body weight reduction). In participants with obesity phenotype of HFpEF, semaglutide improved symptoms, physical limitations and exercise function and reduced inflammation and body weight across obesity categories. In semaglutide-treated patients, the magnitude of benefit was directly related to the extent of weight loss. Collectively, these data support semaglutide-mediated weight loss as a key treatment strategy in patients with obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511.
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- 2023
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13. Screening for type 2 diabetes after a diagnosis of gestational diabetes by ethnicity: A retrospective cohort study.
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Vounzoulaki, Elpida, Khunti, Kamlesh, Miksza, Joanne K., Tan, Bee K., Davies, Melanie J., and Gillies, Clare L.
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Aims: To estimate rates and identify determinants of post-partum glucose screening attendance in women with a history of gestational diabetes mellitus (GDM).Methods: Retrospective cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics, to identify women diagnosed with GDM between 01/01/2000 and 05/11/2018. Age adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models.Results: In 10,868 women with GDM, with an average follow-up of 5.38 years (95% CI 5.31,5.45), there was an average of 3.79 (95% CI 3.70,3.89) screening episodes per individual, with a mean time to first screening test of 1.22 (95% CI 1.18, 1.25) years. South Asian women had a significantly greater likelihood of being screened compared to White women within the first 5 years post-partum, aOR: 1.89 95% CI (1.20,2.98). A low proportion of women received at least one test per year of follow-up (23.87%). Older age at GDM diagnosis, polycystic ovary syndrome, prescribed medication for GDM, and living in England, were all associated with a greater likelihood of being screened.Conclusion: While the majority of women with previous GDM receive at least one glucose screening test within the first 5 years post-partum, fewer than a quarter of them receive on average one test per year of follow-up. Developing strategies to motivate more women to attend screening in primary care is essential. [ABSTRACT FROM AUTHOR]- Published
- 2022
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14. The effectiveness of a structured group education programme for people with established type 2 diabetes in a multi-ethnic population in primary care: A cluster randomised trial.
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Dallosso, Helen, Mandalia, Panna, Gray, Laura J., Chudasama, Yogini V., Choudhury, Sopna, Taheri, Shahrad, Patel, Naina, Khunti, Kamlesh, and Davies, Melanie J.
- Abstract
Background and Aims: Structured self-management education has been shown to be effective in type 2 diabetes (T2DM) but more research is needed to look at culturally appropriate programmes in ethnic minority groups, where prevalence of T2DM is higher and diagnosis earlier. The study tested the effectiveness of a group education programme for people with established T2DM in a multi-ethnic primary care population.Methods and Results: Cluster randomised trial conducted in two multi-ethnic UK sites. Practices were randomised (1:1) to a structured T2DM group education programme or to continue with routine care. A culturally-adapted version was offered to South Asians, who formed the majority of ethnic minority participants. Other ethnic minority groups were invited to attend the standard programme. Primary outcome was change in HbA1c at 12 months. All analyses accounted for clustering and baseline value.367 participants (64(SD 10.8) years, 36% women, 34% from minority ethnic groups) were recruited from 31 clusters. At 12 months, there was no difference in mean change in HbA1c between the two groups (-0.10%; (95% CI: -0.37, 0.17). Subgroup analyses suggested the intervention was effective at lowering HbA1c in White European compared with ethnic minority groups. The intervention group lost more body weight than the control group (-0.82 kg at 6 months and -1.06 kg at 12 months; both p = 0.03).Conclusion: Overall, the programme did not result in HbA1c improvement but in subgroup analysis, a beneficial effect occurred in White Europeans. Findings emphasise a need to develop and evaluate culturally-relevant programmes for ethnic minority groups. [ABSTRACT FROM AUTHOR]- Published
- 2022
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15. Type 2 diabetes
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Ahmad, Ehtasham, Lim, Soo, Lamptey, Roberta, Webb, David R, and Davies, Melanie J
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Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain. This Seminar offers a clinically focused review of the recent developments in type 2 diabetes care including controversies and future directions.
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- 2022
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16. The impact of lifestyle intervention on left atrial function in type 2 diabetes: results from the DIASTOLIC study
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Alfuhied, Aseel, Gulsin, Gaurav S., Athithan, Lavanya, Brady, Emer M., Parke, Kelly, Henson, Joseph, Redman, Emma, Marsh, Anna-Marie, Yates, Thomas, Davies, Melanie J., McCann, Gerry P., and Singh, Anvesha
- Abstract
Aerobic exercise training and low energy diets have been shown to improve left ventricular remodelling and diastolic function in adults with type 2 diabetes (T2D), albeit with differential effects. The impact of these lifestyle interventions on left atrial (LA) function, however, has not previously been reported. The DIASTOLIC study was a prospective, randomised, open-label, blind endpoint trial, in which 90 people with obesity and T2D and no prevalent cardiovascular disease were randomised to a 12-week intervention of: (i) routine care, (ii) aerobic exercise training, or (iii) low energy (≈ 810 kcal/day) meal replacement plan (MRP). Cardiac magnetic resonance (CMR) imaging was performed pre- and post-intervention. Image analysis included LA volumes (LAV), emptying fraction (LAEF), and LA strain (LAS) corresponding to LA reservoir (LAS-r), conduit (LAS-cd), and booster pump (LAS-bp) function. 73 participants with T2D (mean age 50 ± 6 years, 62% male, body mass index (BMI) 36.1 ± 5.3 kg/m2) completed the trial and had analysable LA images. There was no significant change in CMR measured LA volumetric function (LAV/LAEF) in any group. The routine care group showed no significant change in BMI or LAS. In the MRP group, there were significant reductions in BMI (4.5 kg/m2) and a significant increase in LAS-r and LAS-bp (29.9 ± 7.0 to 32.3 ± 7.0%, p = 0.036 and 14.6 ± 5.3 to 17.2 ± 3.7%, p = 0.034). The exercise group showed a small reduction in BMI (0.49 kg/m2), with no significant change in LAS. Compared to routine care, weight loss via a 12-week MRP, led to improvements in LA filling and contractile function in adults with T2D and obesity. However, these within-group changes were not statistically significant on between-group comparison.
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- 2022
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17. A systematic review and meta-analysis to compare the prevalence of depression between people with and without Type 1 and Type 2 diabetes.
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Farooqi, Aaisha, Gillies, Clare, Sathanapally, Harini, Abner, Sophia, Seidu, Sam, Davies, Melanie J., Polonsky, William H., and Khunti, Kamlesh
- Abstract
Aims: Diabetes can significantly impact quality of life and mental health. However, inconsistencies have been reported in the prevalence of depression in those with Type 1 and Type 2 diabetes, and those without. Systematic reviews also included studies without adequate control subjects. We update existing literature, by comparing depression prevalence between individuals with and without Type 1 and Type 2 diabetes.Methods: A systematic review and meta-analysis. We searched MEDLINE, EMBASE and PSYCHINFO, from January 1985 to August 2021. Studies were excluded if they failed to have an adequate control group, specified type of diabetes, or reported depression prevalence by type of diabetes.Results: 44 studies were selected for inclusion. The prevalence of depression was significantly higher in people with Type 1 (22% vs 13%, OR = 2.10 (95% CI: 1.23, 3.52)), or Type 2 diabetes (19% vs 11%, OR = 1.76 (1.55, 2.01)) compared to those without diabetes. There was no association between study effect size and mean age or gender. Findings did not significantly differ between methods of depression assessment. Prevalence of depression in people with diabetes was higher in studies carried out in specialist care (36%, OR = 3.14 (2.12, 4.63)) compared to those in community or primary care (12%, OR = 1.51 (1.35, 1.70) and in low- and middle-income countries (OR = 2.58 (1.91, 3.50) compared to countries with high income economies (OR = 1.59 (1.39, 1.82)).Conclusions: Depression prevalence remains significant in those with type 1 and type 2 diabetes. Effective chronic disease management in people with diabetes is important, particularly screening and managing depression and diabetes distress in specialist care settings. [ABSTRACT FROM AUTHOR]- Published
- 2022
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18. Effects Of Semaglutide Across The Range Of Left Ventricular Ejection Fraction In Obesity Phenotype Of Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Trial.
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Butler, Javed, Shah, Sanjiv J., Abildstrøm, Steen Z., Altschul, Rebecca Lynn, Borlaug, Barry A., Davies, Melanie J., Hovingh, G. Kees, Kitzman, Dalane W., Møller, Daniél V., Petrie, Mark C., Rasmussen, Søren, Verma, Subodh, and Kosiborod, Mikhail N.
- Abstract
STEP-HFpEF, a 52 week trial conducted in patients with obesity phenotype of heart failure with preserved ejection fraction (HFpEF) and no type 2 diabetes, examined the effects of once-weekly semaglutide 2.4 mg versus placebo on HF-related symptoms, physical limitations, and exercise function, as well as inflammation and body weight (BW). Except for sodium-glucose co-transporter 2 inhibitors, previous HF therapies have shown differential effects across the spectrum of left ventricular ejection fraction (LVEF). In this pre-specified analysis, we investigated the effects of semaglutide on the primary and key secondary endpoints across the range of LVEF in the STEP-HFpEF Trial. STEP-HFpEF randomized 529 participants with symptomatic HF, LVEF ≥45% and body mass index of ≥30 kg/m
2 to receive once weekly semaglutide 2.4 mg or placebo. Key exclusion criteria were prior or planned bariatric surgery, self-reported change in BW >11 pounds (5 kilograms) within 90 days prior to randomization, and a HbA1c level ≥6.5% or prior medical history of diabetes. Dual primary endpoints were change from baseline in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and BW. Confirmatory secondary endpoints included change in 6-minute walk distance (6MWD), hierarchical composite endpoint (death, HF events and change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP). For this analysis, patients were stratified based on baseline LVEF of 45-49%, 50-59%, and ≥60%. The effects of semaglutide versus placebo on the dual primary and confirmatory secondary endpoints were examined across these LVEF categories. Overall, the median LVEF in STEP-HFpEF was 57%; 16.1, 40.6, and 43.3% of participants had LVEF of 45-49%, 50-59%, and ≥60%, respectively. Baseline characteristics of patients in the three LVEF based sub-groups are shown in the Table. The effects of semaglutide compared with placebo on the dual primary and confirmatory secondary outcomes across these LVEF categories will be presented. STEP-HFpEF is the first clinical trial of pharmacotherapy to specifically target the obesity phenotype of HFpEF. In this pre-specified analysis, we will examine whether the effects of semaglutide on symptoms, physical limitations, exercise function, as well as inflammation and BW in this patient population are consistent across the range of LVEF. [ABSTRACT FROM AUTHOR]- Published
- 2024
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19. A cost comparison of an enhanced primary care diabetes service and standard care.
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Seidu, Samuel, Gillies, Clare, Farooqi, Azhar, Trivedi, Hina, Than, Tun, Brady, Emer, Davies, Melanie J., and Khunti, Kamlesh
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RESEARCH ,FAMILY medicine ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,TYPE 2 diabetes ,NATIONAL health services ,PRIMARY health care ,COMPARATIVE studies ,COST effectiveness ,RESEARCH funding - Abstract
Background: Type 2 diabetes, which contributes 90% of all cases of diabetes mellitus is now mostly managed in the primary care settings in the UK and other advanced health care systems. The UK National Health Service as a whole could potentially benefit if more patients were managed in primary care settings since primary care-based care is likely to be more cost-effective. We initially compared eight larger general practices (Enhanced practices) in Leicester, UK with neighbouring smaller practices (Core practices) matched for comparable demographic characteristics. Even though this initial study did not find any statistically significant differences in terms of clinical outcomes there was trend in favour of the enhanced practices. In this current study, we conducted a cost comparison of enhanced practice model of diabetes care, to standard care delivered in the core practices.Methods: Data and information were combined from a number of sources and a cost comparison evaluation was carried out in WinBUGs. A probabilistic approach was taken, to allow uncertainty to be included around analysis parameters where appropriate. The analysis evaluated a straight-forward cost comparison of enhanced versus standard care.Results: The cost per person with diabetes per year was £255 (95% CrI 175, 380) in the core practices and £173 (95% CrI 96, 291) in the enhanced practices, resulting in an annual cost saving of -£83 (95% CrI -148, -28) per patient. If the enhanced model of diabetes care were delivered across all the practices in the UK, the cost would be £575,100,000 (95% CrI 320,700,000, 970,700,000), resulting in an annual cost saving of -276,200,000 (95% CrI -495,400,000, -94,480,000).Conclusion: A cost comparison analysis of our larger enhanced primary care based diabetes service confirms significant cost saving, probably driven by economies of scale. These benefits could be multiplied manifold if the service was implemented nationally. [ABSTRACT FROM AUTHOR]- Published
- 2021
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20. Association of ethnicity and socioeconomic status with health outcomes in women with gestational diabetes: Clinical practice research datalink cohort study.
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Vounzoulaki, Elpida, Miksza, Joanne K., Zaccardi, Francesco, Tan, Bee K., Davies, Melanie J., Khunti, Kamlesh, and Gillies, Clare L.
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To investigate in women with prior gestational diabetes mellitus (GDM), differences by ethnicity and socioeconomic status in the incidence of recurrent GDM, type 2 diabetes (T2D), hypertension, and depression. This was a retrospective cohort study including 10,868 women diagnosed with GDM in the Clinical Practice Research Datalink (CPRD GOLD) between January 01, 2000 and November 05, 2018. Linked data were obtained for Hospital Episode Statistics and the Index of Multiple Deprivation. We estimated incidence rates and hazard ratios, by ethnicity and socioeconomic status. During a follow-up of 58,479 person years (mean (SD): 5.38 (3.67) years), the crude incidence was 9.67 (95 % confidence interval: 9.30–10.00) per 100 person years for recurrent GDM, 3.86 (3.70–4.02) for depression, 2.15 (2.03–2.27) for T2D and 0.89 (0.81–0.97) for hypertension. South Asian ethnicity was associated with an increased risk of T2D compared to White (adjusted hazard ratio: 1.65; 1.34–2.05) and Black ethnicity was associated with a greater risk of hypertension (2.93; 1.93–4.46). Black and South Asian ethnicity were associated with a reduced risk of depression compared to White: 0.23 (0.13–0.39) and 0.37 (0.29–0.46), respectively. Incidence rates were higher for all conditions with increasing deprivation level. The risk of health complications in women with a prior history of GDM differs by ethnicity and socio-economic status, suggesting the opportunity for targeted assessment in the years following pregnancy. These findings may inform future guidelines on screening for health outcomes in women with GDM. • Gestational diabetes (GDM) is increasingly prevalent and is associated with serious adverse maternal health outcomes. • South Asian women with prior GDM had a greater risk of developing type 2 diabetes compared to White. • Black women were found to have a greater risk of hypertension, compared to White women, following GDM. • There is an opportunity for targeted screening and preventative interventions following pregnancy complicated by GDM. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Benefits of sodium glucose cotransporter 2 inhibitors across the spectrum of cardiovascular diseases
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Gulsin, Gaurav S, Graham-Brown, Matthew P M, Squire, Iain B, Davies, Melanie J, and McCann, Gerry P
- Abstract
Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a class of medications with positive cardiovascular (CV) effects across a spectrum of patients with and without type 2 diabetes (T2D). In heart failure with reduced ejection fraction, there is clear evidence that SGLT2i reduce hospitalisations and mortality regardless of the presence of diabetes, and they are now recognised as the fourth pillar of pharmacological management. Recent trial data also indicate promising effects in heart failure with preserved ejection fraction. In patients with T2D and atherosclerotic CV diseases, multiple CV outcomes trials have shown reductions in major adverse CV events. Meta-analysis of these trials also shows lower rates of incident and recurrent atrial fibrillation with SGLT2i. Concerns regarding utilisation in patients with chronic kidney disease have been allayed in trials showing SGLT2i in fact have renoprotective effects. Questions still remain regarding the safety of SGLT2i in the acute heart failure setting and immediately post myocardial infarction, as well as in patients with more advanced stages of chronic kidney disease. Furthermore, studies are underway evaluating SGLT2i in patients with heart valve disease, where positive effects on left ventricular remodelling may, for example, improve functional mitral regurgitation. In this review, we summarise the available evidence of recent CV outcomes trials of SGLT2i, focusing particularly on the application of these agents across various CV diseases. We detail evidence to support increased utilisation of these drugs, which in many cases will reduce mortality and improve quality of life in patients routinely encountered by the CV specialist physician.
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- 2022
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22. Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19
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Norris, Tom, Razieh, Cameron, Zaccardi, Francesco, Yates, Thomas, Islam, Nazrul, Gillies, Clare L, Chudasama, Yogini V, Rowlands, Alex V, Davies, Melanie J, McCann, Gerry P, Banerjee, Amitava, Lam, Carolyn S P, Docherty, Annemarie B, Openshaw, Peter JM, Baillie, J Kenneth, Semple, Malcolm Gracie, Lawson, Claire Alexandra, and Khunti, Kamlesh
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ObjectiveUsing a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death.MethodsA multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death.ResultsOf 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication.ConclusionsIn hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.
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- 2022
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23. Association and relative importance of multiple risk factor control on cardiovascular disease, end-stage renal disease and mortality in people with type 2 diabetes: A population-based retrospective cohort study.
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Usman, Muhammad, Khunti, Kamlesh, Davies, Melanie J, and Gillies, Clare L
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Aims: To evaluate the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality, when implementing a multifactorial optimal control approach in primary care in the United Kingdom (UK), in individuals with newly diagnosed type 2 diabetes.Materials and Methods: A retrospective cohort of 53 942 patients were stratified into 1 of the 8 groups according to whether glycated haemoglobin (HbA1c), blood pressure (BP) and total cholesterol (TC) target values were achieved or not from baseline to the date of last follow-up. Those with single or combinations of risk factor control targets achieved, were compared to those who achieved no targets in any of the risk factor. Hazard ratios from the Cox proportional hazards models were estimated against patients who achieved no targets.Results: Of 53 942 patients with newly diagnosed type 2 diabetes, 28%, 55%, and 68% were at target levels for HbA1c <48mmol/mol (<6.5%), BP<140/85mm Hg, and TC<5mmol/L respectively, 36%, 40%, and 12% were at target levels for any one, two, or all three risk factors respectively. Being at HbA1c, BP, and TC targets was associated with an overall 47%, 25%, 42%, 55% and 42% reduction in the risk of ischemic heart disease, cerebrovascular disease, ESRD, cardiovascular-mortality, and all-cause-mortality respectively. Among all subgroups, the risk reduction of study outcome events was greater in the subgroups of patients with microalbuminuria, males, smokers, and patients with BMI≥30kg/m2.Conclusions: Optimal levels of HbA1c, BP, and TC occurring together in patients with newly diagnosed type 2 diabetes are uncommon. Achieving multiple risk factor control targets could substantially reduce the risk of CVD, ESRD and mortality. [ABSTRACT FROM AUTHOR]- Published
- 2021
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24. Prevention of Microvascular Complications of Diabetes
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Crasto, Winston, Patel, Vinod, Davies, Melanie J., and Khunti, Kamlesh
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Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. This review discusses the microvascular complications of diabetes, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy, and provides best practice clinical care recommendations to guide health care professionals to better manage people with these conditions.
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- 2021
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25. Risk of cancer incidence and mortality associated with diabetes: A systematic review with trend analysis of 203 cohorts.
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Ling, Suping, Brown, Karen, Miksza, Joanne K., Howells, Lynne M., Morrison, Amy, Issa, Eyad, Yates, Thomas, Khunti, Kamlesh, Davies, Melanie J., and Zaccardi, Francesco
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Aim: Whether the relative risk of cancer incidence and mortality associated with diabetes has changed over time is unknown.Data Synthesis: On August 12th, 2020, we electronically searched for observational studies reporting on the association between diabetes and cancer. We estimated temporal trends in the relative risk of cancer incidence or mortality associated with diabetes and calculated the ratio of relative risk (RRR) comparing different periods. As many as 193 eligible articles, reporting data on 203 cohorts (56,852,381 participants; 3,735,564 incident cancer cases; 185,404 cancer deaths) and covering the period 1951-2013, were included. The relative risk of all-site cancer incidence increased between 1980 and 2000 [RRR 1990 vs.1980: (1.24; 95% CI: 1.16, 1.34); 2000 vs.1990: (1.23; 1.15, 1.31)] and stabilised thereafter at a relative risk of 1.2; the relative risk of all-site cancer mortality was constant at about 1.2 from 1980 to 2010. Both magnitudes and trends in relative risk varied across cancer sites: the relative risk of colorectal, female breast, and endometrial cancer incidence and pancreatic cancer mortality was constant during the observed years; it increased for bladder, stomach, kidney, and pancreatic cancer incidence until 2000; and decreased for liver while increased for prostate, colon and gallbladder cancer incidence after 2000.Conclusions: Alongside the increasing prevalence of diabetes, the temporal patterns of the relative risk of cancer associated with diabetes may have contributed to the current burden of cancer in people with diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2021
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26. Clustering of comorbidities
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Chudasama, Yogini V, Khunti, Kamlesh, and Davies, Melanie J
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Within the last decade, clustering of comorbidities has become an increasing health problem on a global scale and will continue to challenge healthcare professionals in the coming years. People with multiple diseases find difficulties in managing their daily lives due to the implications each disease brings; attending and keeping up to date with hospital appointments, being prescribed and taking various medications, the effects of mental health and quality of life, and the impact it has on their families. Most research in clinical trials often exclude individuals with multimorbidity and observational studies mainly focus on single disease outcomes, therefore there is an opportunity to encourage future research in an area which could help prevent further cases and improve the lives of those already living with multimorbidity. This review aims to summarise the rising prevalence and most common clusters, highlight the challenges faced in healthcare, and explore ways to improve future research.
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- 2021
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27. Mortality risk comparing walking pace to handgrip strength and a healthy lifestyle: A UK Biobank study
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Zaccardi, Francesco, Franks, Paul W, Dudbridge, Frank, Davies, Melanie J, Khunti, Kamlesh, and Yates, Thomas
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- 2021
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28. Microvascular Disease and Risk of Cardiovascular Events and Death From Intensive Treatment in Type 2 Diabetes
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Kloecker, David E., Khunti, Kamlesh, Davies, Melanie J., Pitocco, Dario, and Zaccardi, Francesco
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To assess whether the presence of microvascular complications modifies the effect of intensive glucose reduction on long-term outcomes in patients with type 2 diabetes.
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- 2021
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29. Relevance of physical function in the association of red and processed meat intake with all-cause, cardiovascular, and cancer mortality.
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Argyridou, Stavroula, Zaccardi, Francesco, Davies, Melanie J., Khunti, Kamlesh, and Yates, Thomas
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Background and Aims: Intake of red and processed meat has been associated with a higher risk of morbidity and mortality; it is unknown whether these associations are modified by overall physical health. This study examined the associations of red and processed meat consumption with all-cause, cardiovascular, and cancer mortality and investigated whether markers of physical function modified the associations.Methods and Results: This observational cohort study used UK Biobank data derived from 419,075 participants free from cancer and cardiovascular disease. Cox models assessed the association of red and processed meat consumption (obtained from a baseline food frequency questionnaire) with mortality, adjusted for potential confounders. Objectively measured handgrip strength and self-reported walking pace were used as interaction terms. The median age was 57 (interquartile range, 49-63) years and 54.9% were women. Over 7 years of follow-up, 8586 all-cause, 1660 cardiovascular, and 4812 cancer deaths occurred. Each additional serving per week of red and processed meat was associated with a hazard ratio (HR) of 1.037 (95% CI: 1.028-1.047) for all-cause; 1.030 (1.009-1.051) for cardiovascular; and 1.029 (1.016-1.042) for cancer mortality. The association of red and processed meat consumption was modified by walking pace, with brisk walkers having the lowest risk per additional serving for all-cause and cancer mortality (HR 1.025; 1.006-1.045 and 1.015; 0.990-1.040, respectively); no interaction was observed for handgrip strength.Conclusion: The known risk of mortality associated with red and processed meat consumption may be lower in those with high physical function. [ABSTRACT FROM AUTHOR]- Published
- 2019
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30. Effect of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on time to outcome in type 2 diabetes cardiorenal outcome trials.
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Rizzi, Alessandro, Kloecker, David E., Pitocco, Dario, Khunti, Kamlesh, Davies, Melanie J., and Zaccardi, Francesco
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In randomized controlled trials (RCTs), treatment effects are commonly reported as hazard ratio, a measure often misinterpreted as a relative risk reduction. The acceleration factor (AF) indicates the extent to which a treatment increases/decreases the time before the occurrence of an outcome and gives useful insights in the interpretation of trials' results. Using individual time-to-event data reconstructed from Kaplan-Meier plots, we estimated AFs for the primary outcomes (POs) and all-cause mortality in glucagon-like peptide-1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2-is) cardiorenal outcome trials in subjects with type 2 diabetes. AFs were estimated from 28 Kaplan-Meier plots of 19 RCTs. Compared to placebo, most GLP1-RAs increased the time before the onset of POs (from 9 % to 59 %) and all-cause mortality (from 8 to 13 %). Similarly, SGLT2-is increased time before the onset of POs (from 19 % to 87 %) and all-cause mortality (from 13 % to 42 %). The AFs provide a complementary and easier-to-interpret measure of treatment effect that could be useful to improve the shared decision-making. • The acceleration factor (AF) – how the time before an outcome is increased/decreased – can help interpret trial's result. • Using reconstructed time-to-event data, we estimated AFs for primary outcomes and death in GLP1-RAs and SGLT2-is trials. • AFs provide an easy-to-interpret measure of treatment effect, adding actionable information in clinical decision-making. SUMMARY In a randomised controlled trial, the acceleration factor (AF) indicates the extent to which the occurrence of an outcome is accelerated or delayed by an intervention, providing a complementary, easy-to-interpret measure of treatment effect. We estimated AFs for primary outcomes and all-cause mortality in type 2 diabetes cardiorenal outcome trials. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Obesity, walking pace and risk of severe COVID-19 and mortality: analysis of UK Biobank
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Yates, Thomas, Razieh, Cameron, Zaccardi, Francesco, Rowlands, Alex V., Seidu, Samuel, Davies, Melanie J., and Khunti, Kamlesh
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Obesity is an emerging risk factor for coronavirus disease-2019 (COVID-19). Simple measures of physical fitness, such as self-reported walking pace, may also be important risk markers. This analysis includes 412,596 UK Biobank participants with linked COVID-19 data (median age at linkage = 68 years, obese = 24%, median number of comorbidities = 1). As of August 24th 2020, there were 1001 cases of severe (in-hospital) disease and 336 COVID-19 deaths. Compared to normal weight individuals, the adjusted odds ratio (OR) of severe COVID-19 in overweight and obese individuals was 1.26 (1.07, 1.48) and 1.49 (1.25, 1.79), respectively. For COVID-19 mortality, the ORs were 1.19 (0.88, 161) and 1.82 (1.33, 2.49), respectively. Compared to those with a brisk walking pace, the OR of severe COVID-19 for steady/average and slow walkers was 1.13 (0.98, 1.31) and 1.88 (1.53, 2.31), respectively. For COVID-19 mortality, the ORs were 1.44 (1.10, 1.90) and 1.83 (1.26, 2.65), respectively. Slow walkers had the highest risk regardless of obesity status. For example, compared to normal weight brisk walkers, the OR of severe disease and COVID-19 mortality in normal weight slow walkers was 2.42 (1.53, 3.84) and 3.75 (1.61, 8.70), respectively. Self-reported slow walkers appear to be a high-risk group for severe COVID-19 outcomes independent of obesity.
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- 2021
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32. Guideline recommendations and the positioning of newer drugs in type 2 diabetes care
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Marx, Nikolaus, Davies, Melanie J, Grant, Peter J, Mathieu, Chantal, Petrie, John R, Cosentino, Francesco, and Buse, John B
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Cardiovascular outcome trials in patients with type 2 diabetes at high cardiovascular risk have led to remarkable advances in our understanding of the effectiveness of GLP-1 receptor agonists and SGLT2 inhibitors to reduce cardiorenal events. In 2019, the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and European Society of Cardiology (ESC) published updated recommendations for the management of such patients. We are concerned that ongoing discussions focusing on the differences between the endocrinologists' consensus report from the ADA and EASD and cardiologists' guidelines from the ESC are contributing to clinical inertia, thereby effectively denying evidence-based treatments advocated by both groups to patients with type 2 diabetes and cardiorenal disease. A subset of members from the writing groups of the ADA–EASD consensus report and the ESC guidelines was convened to emphasise where commonalities exist and to propose an integrated framework that encompasses the views incorporated in management approaches proposed by the ESC and the ADA and EASD. Coordinated action is required to ensure that people with type 2 diabetes, cardiovascular disease, heart failure, or chronic kidney disease are treated appropriately with an SGLT2 inhibitor or GLP-1 receptor agonist. In our opinion, this course should be initiated independent of background therapy, current glycaemic control, or individualised treatment goals.
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- 2021
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33. Association of Timing and Balance of Physical Activity and Rest/Sleep With Risk of COVID-19: A UK Biobank Study
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Rowlands, Alex V., Kloecker, David E., Chudasama, Yogini, Davies, Melanie J., Dawkins, Nathan P., Edwardson, Charlotte L., Gillies, Clare, Khunti, Kamlesh, Razieh, Cameron, Islam, Nazrul, Zaccardi, Francesco, and Yates, Tom
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Behavioral lifestyle factors are associated with cardiometabolic disease and obesity, which are risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate whether physical activity, and the timing and balance of physical activity and sleep/rest, were associated with SARS-CoV-2 positivity and COVID-19 severity. Data from 91,248 UK Biobank participants with accelerometer data and complete covariate and linked COVID-19 data to July 19, 2020, were included. The risk of SARS-CoV-2 positivity and COVID-19 severity—in relation to overall physical activity, moderate-to-vigorous physical activity (MVPA), balance between activity and sleep/rest, and variability in timing of sleep/rest—was assessed with adjusted logistic regression. Of 207 individuals with a positive test result, 124 were classified as having a severe infection. Overall physical activity and MVPA were not associated with severe COVID-19, whereas a poor balance between activity and sleep/rest was (odds ratio [OR] per standard deviation: 0.71; 95% confidence interval [CI], 0.62 to 0.81]). This finding was related to higher daytime activity being associated with lower risk (OR, 0.75; 95% CI, 0.61 to 0.93) but higher movement during sleep/rest being associated with higher risk (OR, 1.26; 95% CI, 1.12 to 1.42) of severe infection. Greater variability in timing of sleep/rest was also associated with increased risk (OR, 1.21; 95% CI, 1.08 to 1.35). Results for testing positive were broadly consistent. In conclusion, these results highlight the importance of not just physical activity, but also quality sleep/rest and regular sleep/rest patterns, on risk of COVID-19. Our findings indicate the risk of COVID-19 was consistently approximately 1.2-fold greater per approximately 40-minute increase in variability in timing of proxy measures of sleep, indicative of irregular sleeping patterns.
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- 2021
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34. The LancetCommission on diabetes: using data to transform diabetes care and patient lives
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Chan, Juliana C N, Lim, Lee-Ling, Wareham, Nicholas J, Shaw, Jonathan E, Orchard, Trevor J, Zhang, Ping, Lau, Eric S H, Eliasson, Björn, Kong, Alice P S, Ezzati, Majid, Aguilar-Salinas, Carlos A, McGill, Margaret, Levitt, Naomi S, Ning, Guang, So, Wing-Yee, Adams, Jean, Bracco, Paula, Forouhi, Nita G, Gregory, Gabriel A, Guo, Jingchuan, Hua, Xinyang, Klatman, Emma L, Magliano, Dianna J, Ng, Boon-Peng, Ogilvie, David, Panter, Jenna, Pavkov, Meda, Shao, Hui, Unwin, Nigel, White, Martin, Wou, Constance, Ma, Ronald C W, Schmidt, Maria I, Ramachandran, Ambady, Seino, Yutaka, Bennett, Peter H, Oldenburg, Brian, Gagliardino, Juan José, Luk, Andrea O Y, Clarke, Philip M, Ogle, Graham D, Davies, Melanie J, Holman, Rury R, and Gregg, Edward W
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- 2020
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35. Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study
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Argyridou, Stavroula, Zaccardi, Francesco, Davies, Melanie J, Khunti, Kamlesh, and Yates, Thomas
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Aims The purpose of this study was to quantify and rank the prognostic relevance of dietary, physical activity and physical function factors in predicting all-cause and cardiovascular mortality in comparison with the established risk factors included in the European Society of Cardiology Systematic COronary Risk Evaluation (SCORE).Methods We examined the predictive discrimination of lifestyle measures using C-index and R2in sex-stratified analyses adjusted for: model 1, age; model 2, SCORE variables (age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol).Results The sample comprised 298,829 adults (median age, 57 years; 53.5% women) from the UK Biobank free from cancer and cardiovascular disease at baseline. Over a median follow-up of 6.9 years, there were 2174 and 3522 all–cause and 286 and 796 cardiovascular deaths in women and men, respectively. When added to model 1, self-reported walking pace improved C-index in women and men by 0.013 (99% CI: 0.007–0.020) and 0.022 (0.017–0.028) respectively for all-cause mortality; and by 0.023 (0.005–0.042) and 0.034 (0.020–0.048) respectively for cardiovascular mortality. When added to model 2, corresponding values for women and men were: 0.008 (0.003–0.012) and 0.013 (0.009–0.017) for all-cause mortality; and 0.012 (–0.001–0.025) and 0.024 (0.013–0.035) for cardiovascular mortality. Other lifestyle factors did not consistently improve discrimination across models and outcomes. The pattern of results for R2mirrored those for C-index.Conclusion A simple self-reported measure of walking pace was the only lifestyle variable found to improve risk prediction for all-cause and cardiovascular mortality when added to established risk factors.
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- 2020
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36. Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study
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Argyridou, Stavroula, Zaccardi, Francesco, Davies, Melanie J, Khunti, Kamlesh, and Yates, Thomas
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- 2020
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37. Emerging glucose-lowering therapies: a guide for cardiologists
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Gulsin, Gaurav S, Graham-Brown, Matthew P M, Davies, Melanie J, and McCann, Gerry P
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In recent large-scale cardiovascular outcome trials, two new classes of glucose-lowering medications—sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs)—demonstrated cardiovascular benefits in adults with type 2 diabetes mellitus (T2DM). These findings have prompted growing optimism among clinicians regarding the potential for these agents to reduce the burden of cardiovascular disease in people with T2DM. GLP-1RAs and SGLT2i are now advocated as second-line agents in European and US guidelines for management of both hyperglycaemia and for primary prevention of cardiovascular disease in people with T2DM. Given the high prevalence of T2DM in patients with cardiovascular disease, cardiologists will increasingly encounter these agents in routine clinical practice. In this review, we summarise evidence from cardiovascular outcome trials of GLP-1RAs and SGLT2i, give practical advice on prescribing and detail safety considerations associated with their use. We also highlight areas where further work is needed, giving details on active clinical trials. The review aims to familiarise cardiologists with these emerging treatments, which will be increasingly encountered in clinical practice, given the expanding representation of T2DM in patients with cardiovascular disease. Whether these drugs will be initiated by cardiologists remains to be determined.
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- 2020
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38. Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention
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Selvarajah, Dinesh, Kar, Debasish, Khunti, Kamlesh, Davies, Melanie J, Scott, Adrian R, Walker, Jeremy, and Tesfaye, Solomon
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Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 and 2 diabetes. It is a leading cause of lower-limb amputation and disabling neuropathic pain. Amputations in patients with diabetes have a devastating effect on quality of life and are associated with an alarmingly low life expectancy (on average only 2 years from the amputation). Amputation also places a substantial financial burden on health-care systems and society in general. With the introduction of national diabetes eye screening programmes, the prevalence of blindness in working-age adults is falling. This is not the case, however, with diabetes related amputations. In this Review, we appraise innovative point-of-care devices that enable the early diagnosis of DPN and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN. We also propose a framework for screening and early multifactorial interventions as the best prospect for preventing or halting DPN and its devastating sequelae.
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- 2019
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39. A data-driven, meaningful, easy to interpret, standardised accelerometer outcome variable for global surveillance.
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Rowlands, Alex V., Sherar, Lauren B., Fairclough, Stuart J., Yates, Tom, Edwardson, Charlotte L., Harrington, Deirdre M., Davies, Melanie J., Munir, Fehmidah, Khunti, Kamlesh, and Stiles, Victoria H.
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Our aim is to demonstrate how a data-driven accelerometer metric, the acceleration above which a person's most active minutes are accumulated, can (a) quantify the prevalence of meeting current physical activity guidelines for global surveillance and (b) moving forward, could inform accelerometer-driven physical activity guidelines. Unlike cut-point methods, the metric is population-independent (e.g. age) and potentially comparable across datasets. Cross-sectional, secondary data analysis. Analyses were carried out on five datasets using wrist-worn accelerometers: children (N = 145), adolescent girls (N = 1669), office workers (N = 114), pre- (N = 1218) and post- (N = 1316) menopausal women, and adults with type 2 diabetes (N = 475). Open-source software (GGIR) was used to generate the magnitude of acceleration above which a person's most active 60, 30 and 2 min are accumulated: M60 ACC ; M30 ACC and M2 ACC , respectively. The proportion of participants with M60 ACC (children) and M30 ACC (adults) values higher than accelerations representative of brisk walking (i.e., moderate-to-vigorous physical activity) ranged from 17 to 68% in children and 15 to 81% in adults, tending to decline with age. The proportion of pre-and post-menopausal women with M2 ACC values meeting thresholds for bone health ranged from 6 to 13%. These metrics can be used for global surveillance of physical activity, including assessing prevalence of meeting current physical activity guidelines. As accelerometer and corresponding health data accumulate it will be possible to interpret the metrics relative to age- and sex- specific norms and derive evidence-based physical activity guidelines directly from accelerometer data for use in future global surveillance. This is where the potential advantages of these metrics lie. [ABSTRACT FROM AUTHOR]
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- 2019
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40. Statins and risk of thromboembolism: A meta-regression to disentangle the efficacy-to-effectiveness gap using observational and trial evidence.
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Miksza, Joanne K., Zaccardi, Francesco, Kunutsor, Setor K., Seidu, Samuel, Davies, Melanie J., and Khunti, Kamlesh
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Background and Aims: Meta-analyses of randomised controlled trials (RCTs) and observational studies indicate a lower risk of venous thromboembolism (VTE) associated with statin treatment. We aimed to compare the effect of statin therapy in these two settings and to identify and quantify potential factors to explain statin efficacy and effectiveness.Methods and Results: We electronically searched on December 11th, 2018, articles reporting on first VTE events in RCTs (statin vs placebo) and in observational studies (participants exposed vs non-exposed to statin). We performed Knapp-Hartung random-effect meta-analyses to calculate pooled relative risks (RRs) of VTE events associated with statin treatment, separately for RCTs and observational studies; and estimated the ratio of the relative risk (RRR) comparing RCTs and observational studies using meta-regressions, progressively adjusted for study-level characteristics. Twenty-one RCTs (115,107 participants; 959 events) and 8 observational studies (2,898,096 participants; 19,671 events) were included. Pooled RRs for RCTs and observational studies were 0.82 (95% confidence interval (CI): 0.67-1.00; I2 19.2%) and 0.60 (95% CI: 0.42-0.86; I2 86.3%), respectively. In meta-regressions, the unadjusted RRR indicated a nonsignificant 23% smaller benefit in RCTs (RRR 0.77; 95% CI: 0.52-1.13); accounting for age, sex, geographical region, and duration of follow-up, there was a sensible change of the RRR which resulted 0.30 (95% CI: 0.13-0.68).Conclusion: Differences in the characteristics between patients included in RCTs and those in observational studies may account for the differential effect of statins in preventing VTE in the two settings. [ABSTRACT FROM AUTHOR]- Published
- 2019
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41. Mortality risk comparing walking pace to handgrip strength and a healthy lifestyle: A UK Biobank study
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Zaccardi, Francesco, Franks, Paul W, Dudbridge, Frank, Davies, Melanie J, Khunti, Kamlesh, and Yates, Thomas
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Aims Brisk walking and a greater muscle strength have been associated with a longer life; whether these associations are influenced by other lifestyle behaviours, however, is less well known.Methods Information on usual walking pace (self-defined as slow, steady/average, or brisk), dynamometer-assessed handgrip strength, lifestyle behaviours (physical activity, TV viewing, diet, alcohol intake, sleep and smoking) and body mass index was collected at baseline in 450,888 UK Biobank study participants. We estimated 10-year standardised survival for individual and combined lifestyle behaviours and body mass index across levels of walking pace and handgrip strength.Results Over a median follow-up of 7.0 years, 3808 (1.6%) deaths in women and 6783 (3.2%) in men occurred. Brisk walkers had a survival advantage over slow walkers, irrespective of the degree of engagement in other lifestyle behaviours, except for smoking. Estimated 10-year survival was higher in brisk walkers who otherwise engaged in an unhealthy lifestyle compared to slow walkers who engaged in an otherwise healthy lifestyle: 97.1% (95% confidence interval: 96.9–97.3) vs 95.0% (94.6–95.4) in women; 94.8% (94.7–95.0) vs 93.7% (93.3–94.2) in men. Body mass index modified the association between walking pace and survival in men, with the largest survival benefits of brisk walking observed in underweight participants. Compared to walking pace, for handgrip strength there was more overlap in 10-year survival across lifestyle behaviours.Conclusion Except for smoking, brisk walkers with an otherwise unhealthy lifestyle have a lower mortality risk than slow walkers with an otherwise healthy lifestyle.
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- 2024
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42. Cancer is becoming the leading cause of death in diabetes – Authors' reply
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Davies, Melanie J, Ahmad, Ehtasham, Lim, Soo, Lamptey, Roberta, and Webb, David R
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- 2023
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43. Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals.
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Chudasama, Yogini V., Gillies, Clare L., Zaccardi, Francesco, Coles, Briana, Davies, Melanie J., Seidu, Samuel, and Khunti, Kamlesh
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Routine care for chronic disease is an ongoing major challenge. We aimed to evaluate the global impact of COVID-19 on routine care for chronic diseases. An online survey was posted 31 March to 23 April 2020 targeted at healthcare professionals. 202 from 47 countries responded. Most reported change in routine care to virtual communication. Diabetes, chronic obstructive pulmonary disease, and hypertension were the most impacted conditions due to reduction in access to care. 80% reported the mental health of their patients worsened during COVID-19. It is important routine care continues in spite of the pandemic, to avoid a rise in non-COVID-19-related morbidity and mortality. [ABSTRACT FROM AUTHOR]
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- 2020
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44. Comparative Relevance of Physical Fitness and Adiposity on Life Expectancy
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Zaccardi, Francesco, Davies, Melanie J., Khunti, Kamlesh, and Yates, Tom
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To investigate the extent to which 2 measures of physical fitness—walking pace and handgrip strength—are associated with life expectancy across different levels of adiposity, as the relative importance of physical fitness and adiposity on health outcomes is still debated.
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- 2019
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45. Effect of more versus less intensive blood pressure control on cardiovascular, renal and mortality outcomes in people with type 2 diabetes: A systematic review and meta-analysis.
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Ioannidou, Ekaterini, Shabnam, Sharmin, Abner, Sophia, Kaur, Navjot, Zaccardi, Francesco, Ray, Kausik K., Seidu, Sam, Davies, Melanie J., Khunti, Kamlesh, and Gillies, Clare L.
- Abstract
Currently, there is uncertainty as to whether blood pressure control in patients with type 2 diabetes should be treated to standard recommended levels or more intensively. Medline, EMBASE, CENTRAL, and Clinicaltrials.gov were searched between January 1, 2000 and April 20th, 2023. Outcomes considered were all-cause mortality, stroke, heart failure, cardiovascular disease, albuminuria, coronary heart disease, and renal outcomes. Random-effects meta-analyses estimated pooled relative risks and mean differences. Nine trials enrolling 11,005 participants with type 2 diabetes were included. The pooled mean difference between the intensive and standard treatment groups at follow-up were −7.98 mmHg (95% CI: 12.19 to −3.76) in systolic blood pressure, and −5.08 mmHg (−7.00 to −3.17) in diastolic blood pressure; although between study heterogeneity was high for both meta-analyses (I
2 >85%). Intensive blood pressure lowering resulted in a reduction in risk of stroke (risk ratio 0.64; 0.52 to 0.79), and macro-albuminuria (0.77; 0.63 to 0.93). More intensive blood pressure control did not result in a statistically significant reduction in risk of all-cause mortality, heart failure, cardiovascular death, cardiovascular events, renal outcomes, and micro-albuminuria; although the direction of estimated effect was beneficial for all outcomes. The use of intensive compared with standard blood pressure targets resulted in a significant reduction in blood pressure, stroke, and macro-albuminuria in patients with type 2 diabetes. The post-treatment blood pressure level in the intensive group was 125/73 mmHg, suggesting the current recommendations of 130/80 mmHg blood pressure or lower if tolerated, could be reduced further. • Aiming for a low blood pressure target in participants with T2DM results in a reduced risk of stroke and macro-albuminuria. • No significant difference was found for CVD events or mortality, heart failure, micro-albuminuria, or renal outcomes. • The post-treatment BP level in the intensive group was 125/73 mmHg, suggesting the current recommendations could be reduced. [ABSTRACT FROM AUTHOR]- Published
- 2023
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46. Self-knowledge of HbA1c in people with Type 2 Diabetes Mellitus and its association with glycaemic control.
- Author
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Trivedi, Hina, Gray, Laura J., Seidu, Samuel, Davies, Melanie J, Charpentier, Guillaume, Lindblad, Ulf, Kellner, Christiane, Nolan, John, Pazderska, Agnieszka, Rutten, Guy, Trento, Marina, and Khunti, Kamlesh
- Abstract
Objective: The aim of this study was to evaluate the prevalence of accurate self-knowledge of a patient's own HbA1c level (HbA1cSK), as a component of structural education (University Hospital's of Leicester (UHL), 2013) and its association with glycaemic control.Methods: Data from the GUIDANCE study, a cross-sectional study involving 7597 participants from eight European countries was used. HbA1cSK was evaluated and compared with laboratory measured HbA1c levels (HbA1cLAB), which represented the measure of glycaemic control. Accuracy of the self-reported HbA1c was evaluated by using agreement statistical methods.Results: The prevalence of HbA1cSK was 49.4%. Within this group, 78.3% of the participants had accurately reported HbA1cSK. There was good level of agreement between HbA1cSK and HbA1cLAB (intra-class correlation statistic=0.84, p<0.0001). Participants with accurately reported HbA1cSK were found to have a statistically significantly lower HbA1cLAB compared to participants with inaccurately reported HbA1cSK (7.0% versus 7.3%, p<0.001).Conclusion: Nearly half of the patients had self-knowledge of their own HbA1c level. Moreover, the participants with accurately reported HbA1cSK were found to have associated better glycaemic control. [ABSTRACT FROM AUTHOR]- Published
- 2017
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47. Considerations when using the activPAL monitor in field-based research with adult populations.
- Author
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Edwardson, Charlotte L., Winkler, Elisabeth A.H., Bodicoat, Danielle H., Yates, Tom, Davies, Melanie J., Dunstan, David W., and Healy, Genevieve N.
- Abstract
Research indicates that high levels of sedentary behavior (sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior (and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activPAL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activPAL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activPAL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activPAL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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48. First-line treatment for type 2 diabetes: is it too early to abandon metformin?
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Zaccardi, Francesco, Khunti, Kamlesh, Marx, Nikolaus, and Davies, Melanie J
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- 2020
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49. Progression to Type 2 Diabetes in Women With a Known History of Gestational Diabetes: Systematic Review and Meta-analysis
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Vounzoulaki, Elpida, Khunti, Kamlesh, Abner, Sophia C., Tan, Bee K., Davies, Melanie J., and Gillies, Clare L.
- Abstract
(Abstracted from BMJ2020;369:m1361)Gestational diabetes mellitus (GDM) is an established risk factor for the future development of type 2 diabetes mellitus (T2DM). Systematic reviews of studies that have highlighted the increased risk of developing T2DM after GDM are more than a decade old.
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- 2020
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50. Do sulphonylureas still have a place in clinical practice?
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Khunti, Kamlesh, Chatterjee, Sudesna, Gerstein, Hertzel C, Zoungas, Sophia, and Davies, Melanie J
- Abstract
Sulphonylureas have been commercially available since the 1950s, but their use continues to be associated with controversy. Although adverse cardiovascular outcomes in some observational studies have raised concerns about sulphonylureas, findings from relatively recent, robust, and high-quality systematic reviews have indicated no increased risk of all-cause mortality associated with sulphonylureas compared with other active treatments. Results from large, multicentre, randomised controlled trials such as the UK Prospective Diabetes Study and ADVANCE have confirmed the microvascular benefits of sulphonylureas, a reduction in the incidence or worsening of nephropathy and retinopathy, and no increase in all-cause mortality, although whether these benefits were due to sulphonylurea therapy and not an overall glucose-lowering effect could not be confirmed. A comparison of sulphonylureas and pioglitazone in the TOSCA.IT trial also confirmed the efficacy and cardiovascular safety of sulphonylureas. Investigators of randomised controlled trials have reported an increased risk of hypoglycaemia and weight gain with sulphonylureas, but data from observational studies suggest that the incidence of severe hypoglycaemia is lower in people taking sulphonylurea than in people taking insulin, and weight gain with sulphonylureas has been relatively modest in large cohort studies. 80% of people with diabetes live in low-to-middle income countries, so the effectiveness, affordability, and safety of sulphonylureas are particularly important considerations when prescribing glucose-lowering therapy. Results of ongoing head-to-head studies with new drugs, such as the comparison of glimepiride with linagliptin in the CAROLINA study and the comparison of various therapies (including sulphonylureas) for glycaemic control in the GRADE study, will determine the place of sulphonylureas in glucose-lowering therapy algorithms for patients with type 2 diabetes.
- Published
- 2018
- Full Text
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