Mapping the human genetic architecture of COVID-19 (2021)

Type of publication:Journal article

Author(s):

COVID-19 Host Genetics Initiative. Includes James Moon, Nigel Capps, Sanal Jose, Colene Adams, Anita Agasou, Amy Bowes, Pauline Boyle, Mandy Carnahan, Anne Carter, Danielle Childs, Kelly Hard, Yasmin Hussain, Michael Leigh, Rachel Rikunenko, Jo Stickley, Helen Tivenan, Rebecca Wilcox, Tracie Arden, Mandy Beekes, Heather Button, Denise Donaldson, Fran Hurford, Ayesha Javaid, James Jones, Terry Martin, Helen Millward, Nichola Motherwell, Julie Summers, Louise Ting & Louise Tonks of Shrewsbury and Telford Hospital NHS Trust

Citation:Nature. 2021, Vol. 600(7889) (pp 472-477)

Abstract:The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19<sup>1,2</sup>, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases<sup>3-7</sup>. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Link to full-text (open access - no password required)

Altmetrics:

Acute cholecystectomy in elderly - age is not a limit (2021)

Type of publication:
Conference abstract

Author(s):
*Gupta A.; *Rashid M.U.; *Rupasinghe N.; *Adjepong S.; *Rink J.; *Kirby G.; *Jain R.; *Riera M.; *Parampalli U.; *Pattar J.

Citation:
British Journal of Surgery. Conference: UGI Congress 2021. Belfast United Kingdom. 108 (SUPPL 9) pp. ix34

Abstract:
Background: Acute or hot cholecystectomy (AC) has been established as a safe and efficacious modality of managing acute biliary pathology. However, it has been performed with caution in the elderly (defined by the world health organisation as patients over the age of 65). The NICE guidance in this area does not preclude this practise on elderly patients. Our acute cholecystectomy service treats patients of all ages according to performance status and fitness for surgery rather than age we audited our results in this age group. Method(s): All patients over the age of 65 who underwent acute cholecystectomy in the dedicated emergency cholecystectomy lists were audited from the period starting 31st December 2019 to 31st June 2021. Patient demographics, co-morbidies and surgical factors were recorded. The primary outcomes measure was in hospital stay and readmission, secondary outcome were complications and perioperative mortality. Result(s): 41 elderly patients underwent AC during the audit period, (male 18: female 23). Majority of patients had acute cholecystitis 30(73%). The median inpatient stay following surgery was 2 days(range 2-5 days) and the median admission to surgery time was 6 days (range 5-12 days). Only 3(7%) patients had a subtotal cholecystectomy. There was only 3 complications from surgery which were all between a clavien-dindo score of 2 and 3. There were 3 readmission in the immediate post-operative period. There was one 30-day mortality which was from necrotising pancreatitis as a result of ERCP and not from the operation. Conclusion(s): Acute cholecystectomy in this age group appears to be safe and effective way to treat acute biliary pathology and compares similarly to the outcomes in the younger

Managing hypertension in type 2 diabetes – the basics (2021)

Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(6)

Abstract:Brought to you by Diabetes & Primary Care, this interactive case study takes you through the basic considerations of managing hypertension in type 2 diabetes. The scenario is not unusual and is one that, as a primary healthcare worker, you could easily be confronted with. By actively engaging with this case history, you should feel more confident and empowered to manage effectively such a problem in the future.

Fatty liver disease and type 2 diabetes (2021)

Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(5)

Abstract:This interactive case study, presented by Diabetes & Primary Care, takes you through the necessary considerations in managing fatty liver disease in an individual with type 2 diabetes. The scenario is not unusual and is one that, as a primary healthcare worker, you could easily be confronted with. By actively engaging with this case history, you should feel more confident and empowered to manage effectively such a problem in the future.

Steroid-induced hypoglycaemia (2021)

Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(4)

Abstract:Brought to you by Diabetes & Primary Care, the three mini-case studies presented below take you through what it is necessary to consider in identifying and managing steroid-induced hyperglycaemia. Each scenario provides a different set of circumstances that you could meet in your everyday practice. By actively engaging with them, you will feel more confident and empowered to manage effectively such problems in the future.

Hypoglycaemia and type 2 diabetes (2021)

Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(4)

Abstract:Brought to you by Diabetes & Primary Care, the four mini-case studies presented below will help you to consider what constitutes hypoglycaemia, what its causes and risk factors are in type 2 diabetes, how to detect and manage it in primary care, and strategies for minimising the risk. Each scenario provides a different set of circumstances that you could meet in your everyday practice. By actively engaging with them, you will feel more confident and empowered to manage effectively such problems in the future.

Making a diagnosis in type 2 diabetes (2021)

Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(2)

Abstract:Brought to you by Diabetes & Primary Care, the three mini-case studies presented below take you through what it is necessary to consider in making an accurate diagnosis of type 2 diabetes. Each scenario provides a different set of circumstances that you could meet in your everyday practice. By actively engaging with them, you will feel more confident and empowered to manage effectively such problems in the future.

Diabetic nephropathy and type 2 diabetes (2021)

Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(1)

Abstract:This interactive case study, presented by Diabetes & Primary Care, takes you through the necessary considerations in managing diabetic nephropathy in an individual with type 2 diabetes. The scenario is not unusual and is one that, as a primary healthcare worker, you could easily be confronted with. By actively engaging with this case history, you should feel more confident and empowered to manage effectively such a problem in the future.

Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study (2021)

Type of publication:Journal article

Author(s):Harvey P.R.; McKay S.C.; Wilkin R.J.W.; Layton G.R.; Powell-Brett S.; Okoth K.; Trudgill N.; Roberts K.J.; Baker G.; Brom M.K.; Brown Z.; Farrugia A.; Haldar D.; Kalisvaart M.; Marley A.; Pande R.; Patel R.; Stephenson B.T.F.; Baillie C.; Croitoru C.; Eddowes P.J.; Elshaer M.; Farhan-Alanie M.M.; Laing R.; Mann K.; Materacki L.; Nandi S.; Pericleous S.; Prasad P.; Rinkoff S.; Selvaraj E.; Shah J.; Sheel A.R.G.; Szatmary P.; Williams P.; Milburn J.; Bekheit M.; Ghazanfar M.; Curry H.; Persson P.; Rollo A.; Thomson R.; Harper S.; Varghese S.; Collins J.; Stupalkowska W.; Afzal Z.; Badran A.; Barker J.; Hakeem A.; Kader R.; Saji S.; Sheikh S.; Smith A.C.D.; Stasinos K.; Steinitz H.; Malik H.; Burston C.; Carrion-Alvarez L.; Shiwani M.; Ahmad G.; Allen T.; Darley E.; Patil S.; Brooks C.; Cresswell B.; Welsh F.; Cook C.; Smyth R.; Booth R.; West M.; King A.; Tucker O.; Phelan L.; Burahee A.; Devogel C.; Javed A.; Kay R.; Khan S.; Leet F.; Troth T.; Ward A.; Young J.; Murray E.; Gray T.; Johnson R.; Lockwood S.; Young R.; Zhou G.; Portal J.; Rees J.; Arnold B.; Scroggie D.; Abeysekera K.W.M.; Asif A.; Hay F.; Maccabe T.; Pathak S.; Robertson H.; Sandberg C.; Woodland H.; Charalabopoulos A.; Kordzadeh A.; Anderson J.; Napier D.; Hodges P.; Jones G.; Sheiybani G.; Archer T.; Khan A.; Kirk S.; Walker N.; Hassam U.; Wong I.; Silva M.; Jones K.; Allen J.; Abbas S.H.; Harborne M.; Majid Z.; Eardley N.; Reilly I.; Wadsworth P.; Bell C.; Holloway K.; Stockton W.; Thomas R.; Williams K.J.; Canelo R.; Tay Y.; Adnan M.; Aroori S.; Rajaretnam N.; Rekhraj S.; Wilkins A.; Nelapatia R.; Verebcean M.; Braithwaite S.; Apollos J.; Robertson N.; Belgaumkar A.; Brant A.; Shahdoost A.; French J.J.; Sen G.; Thakkar R.; Kanwar A.; Klaptocz J.; Rodham P.; O'Riordan B.; Maharaj G.; Davies M.; Higgs S.; Cutting J.; Joseph M.; Backhouse L.; Butler J.; Cooper J.; O'nions T.; Shaukat S.; Kumar A.; George V.; Ingmire J.; Saha A.; Coe P.; Noor R.; Lykoudis P.; Elshaer A.; Andreou A.; Clarke T.; Davies O.; Rimmer P.; Kanakala V.; Mitra V.; Akol G.; Burgess M.; Elzubier M.; Jones R.; Majumdar D.; Wescott H.; Bailey A.; Gomez M.; Herman O.; Deguara J.; Whitehead-Clarke T.; Gorard L.; Law R.; Leung L.Y.; Whitelaw D.; Adil M.; Krivan S.; Waters J.; Fernandes R.; Mealey L.; Merh R.; Okaro A.; Shepherd J.; O'Reilly D.; Pilkington J.; Hussain Z.; Ingram S.; Stott M.C.; Abbott S.; Bhamra N.; Hirri F.; Lee K.; Murrell J.; Resool S.; Taylor M.; King M.; Madhotra R.; Ayubi H.; Ali J.; Chander N.; Mckune G.; Wothers T.; Shingler G.; Mortimer M.; Dykes K.; Edwards H.; Menon S.; Gautham A.; Ali I.; Anjum R.; Brookes M.; Wilkinson B.; Tait I.; Noaman I.; Wilson M.; Mogan S.; Rushbrook S.; Hyde S.; Baker S.; Hall P.; Lucas H.; Pease J.; Millar A.; Tariq Z.; Blad W.; Cunningham M.; Hall M.; Luthra P.; Seymour K.; Aawsaj Y.; Jones M.; Elliott D.; Finch J.G.; Rajjoub Y.; Gupta A.; Molloy P.; Mykoniatis I.; Atallah E.; Albraba E.; Asimba V.; Baxter A.; Chin A.; Vojtekova K.; Ong L.; Modi H.N.; Muscara F.; Perry M.; Katz C.; Shaban N.; Dichmont L.; Dissanayake T.; Mostafa W.; Ghosh D.; Hwang S.; Bajomo O.; Lloyd T.; Wye J.; Holt A.; Pathanki A.; Townsend S.; Babar N.; Giovinazzo F.; Kennedy L.; Kandathil M.; King D.; Pillai M.; Glen P.; Holroyd D.; Drozdzik S.; Kourounis G.; Thompson J.; McNally S.; Thomas I.; Reddy Y.; Subar D.; Heywood N.; Khoo E.; Austin A.; Awan A.; Tan H.; Kasi M.; Prasad S.; Baqai M.; Abd Alkoddus M.; Al-Allaf O.; Mitchell K.; Mole S.; Yoong A.; Fusai G.; Brown S.; Bulathsinhala S.; Gilliland J.; Boyce T.; Al-Ardah M.; Matthews E.; Wakefield C.; Hou D.; Thomasset S.; Guest R.; Falconer S.; Hughes M.; Johnston C.; Kung J.W.C.; Lee E.; McNally E.; Sherif A.E.; Stutchfield B.; Baron R.D.; Dunne D.F.J.; Dickerson L.D.; Exarchou K.E.; Knight E.; Whelan P.; Hutchins R.; Wilson P.; Phillpotts S.; Badrulhisham F.; Dawes A.; Derwa Y.; Rajagopal S.; Ramoutar S.; Vaik T.; Bhogal R.H.; McLaren N.; Policastro T.; *Butterworth J.; *Riera M.; *Ismail A.; *Ahmed A.; *Alame R.; *Alford K.; *Banerjee S.; *Bull C.; *Kirby G.; Athwal T.; Hebbar S.; Ishtiaq J.; Kamran U.; Abbasi A.; Kamarul-bahrin M.; Banks A.; Khalil A.; Karanjia N.; Trivedi D.; Chakravaratty S.; Frampton A.; Gabriella J.; Pinn G.; Colleypriest B.; Betteridge F.; Murugiah D.; Rossiter A.; Yong K.; Sellahewa C.; Chui K.; Ehsan A.; Fisher N.; Iyer S.; McMurtry H.; Garbutt G.; Mahgoub S.; Alleyne L.; Harvey J.; Johnson K.; Richards E.; Palaniyappan N.; Bowler C.; Inumerable R.; Abu M.; Suhool A.; Talbot T.; Westwood J.; Zumbo G.; Osborne A.; Botes A.; Dyer S.; Thomas-Jones I.; Merker L.; Przemioslo R.; Roderick M.; Valverde J.; Zerafa A.; Barker S.; Wan A.; Lalani R.; Barrett C.; Kapirial N.; McCarthney K.; Ramamoorthy R.; Yalchin M.; Huggett M.; Macutkiewicz C.; Smith A.; Buchanan A.; Burke J.; Goodchild G.; Keane M.G.; Potts J.; Disney B.; McFarlane M.; Baker E.; Bullock S.; Coleman S.; Mcardle C.; Morgan J.; Mozdiak E.; Obisesan A.; O'Flynn L.; Mowbray N.; de Berker H.T.; Driscoll P.; Alberts J.C.; Sadien I.D.; Webb K.; Khalil H.; Parmar C.; Sadigh D.; Seyed-Safi P.; Shala L.; Somasundaram M.; Bryce G.; McCormack K.; Jamieson W.; Mitchell L.; Cheung D.; Hicken B.; Abbas N.; Kurian A.; Tahir I.; Spearman J.; Johnston T.; Jones C.

Citation:Pancreatology; Sep 2021; vol. 21 (no. 6); p. 1127-1134

Abstract:Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design(s): RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Result(s): Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5-7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion(s): Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required.

Altmetrics: