Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476) (2022)

Type of publication:Randomised controlled trial

Author(s):James N.D.; Clarke N.W.; Cook A.; Ali A.; Hoyle A.P.; Attard G.; Brawley C.D.; Chowdhury S.; Cross W.R.; Dearnaley D.P.; de Bono J.S.; Montana C.D.; Gilbert D.; Gillessen S.; Gilson C.; Jones R.J.; Langley R.E.; Malik Z.I.; Matheson D.J.; Millman R.; Parker C.C.; Pugh C.; Rush H.; Russell J.M.; Berthold D.R.; Buckner M.L.; Mason M.D.; Ritchie A.W.; Birtle A.J.; Brock S.J.; Das P.; Ford D.; Gale J.; Grant W.; Gray E.K.; Hoskin P.; Khan M.M.; Manetta C.; McPhail N.J.; O'Sullivan J.M.; Parikh O.; Perna C.; Pezaro C.J.; Protheroe A.S.; Robinson A.J.; Rudman S.M.; Sheehan D.J.; *Srihari N.N.; Syndikus I.; Tanguay J.; Thomas C.W.; Vengalil S.; Wagstaff J.; Wylie J.P.; Parmar M.K.; Sydes M.R.

Citation:
International Journal of Cancer. 151(3) (pp 422-434), 2022. Date of Publication: 01 Aug 2022.

Abstract:Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multi-arm, multi-stage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3yrs after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomized patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000mg+prednisolone 5mg (SOC+AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors. 1003 patients were contemporaneously randomized (Nov-2011–Jan-2014): median age 67yr; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% un-assessable; median PSA 97ng/mL. At 6.1yr median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC+AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95%CI:0.50-0.71; P =0.31×10-9 ) favoured SOC+AAP, with 5-yr survival improved from 41% SOC-alone to 60% SOC+AAP. This was similar in low-risk (HR = 0.55; 95%CI:0.41-0.76) and high-risk (HR = 0.54; 95%CI:0.43-0.69) patients. Median and current maximum time on SOC+AAP was 2.4yr and 8.1yr. Toxicity at 4yr post-randomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC+abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

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Patient Outcomes Related to In-Hospital Delays in Appendicectomy for Appendicitis: A Retrospective Study (2022)

Type of publication:
Journal article

Author(s):
Claydon O; Down B; *Kumar S

Citation:
Cureus, 2022 Mar 10; Vol. 14 (3), pp. e23034

Abstract:
Background and objective In many hospitals, the availability of operating theatres and access to senior surgical and anaesthetic support diminish during night hours. Therefore, urgent surgery is sometimes postponed until the following morning rather than performed overnight, if it is judged to be safe. In this study, we aimed to determine if a delay in laparoscopic appendicectomy in cases of acute appendicitis of over 12 hours, analogous to an overnight delay, correlated with worse patient outcomes. Our primary outcome was delayed discharge from the hospital. Our secondary outcomes were appendicitis severity, conversions, and postoperative complications. Methods We undertook a retrospective review of the medical records of patients who underwent laparoscopic appendicectomy for appendicitis at a UK district general hospital between 01/01/2018 and 30/08/2019. For each patient, clinical and demographic information, and time of hospital admission, surgery, and discharge were collected. Delayed discharge was defined as "time to discharge" >24 hours after surgery. Results A total of 446 patients were included in the study. In 137 patients (30.7%), "time to surgery" was under 12 hours; in 309 patients (69.3%) "time to surgery" was over 12 hours. Of note, 319 patients (71.5%) had a delayed discharge; 303 patients (67.9%) had complicated appendicitis, and 143 patients had severe appendicitis (32.1%). No statistically significant association between "time to surgery" and delayed discharge, appendicitis severity, conversion, or 30-day re-presentations was observed. Conclusion Time from admission to the start of appendicectomy did not affect patient outcomes. Short in-hospital delays in appendicectomy, such as an overnight delay, may be safe in certain patients and should be determined based on clinical judgement.

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Endoscopically assisted reconstruction of chronic Achilles tendon ruptures and re-ruptures using a semitendinosus autograft is a viable alternative to pre-existing techniques (2022)

Type of publication:
Journal article

Author(s):
Nilsson N; Gunnarsson B; *Carmont MR; Brorsson A; Karlsson J; Nilsson Helander K

Citation:
Knee Surgery, Sports Traumatology, Arthroscopy : official journal of the ESSKA, 2022 Apr 09 [epub ahead of print]

Abstract:
Purpose: Achilles tendon ruptures are termed chronic after a delay in treatment for more than 4 weeks. The literature advocates surgical treatment with reconstruction to regain ankle push-off strength. The preferred technique is, however, still unknown and is often individualized. This study aims to present the technique and clinical outcome of an endoscopically assisted free semitendinosus reconstruction of chronic Achilles tendon rupture and Achilles tendon re-ruptures with delayed representation. It is hypothesized that the presented technique is a viable and safe alternative for distal Achilles tendon ruptures and ruptures with large tendon gaps.
Method: Twenty-two patients (13 males and 9 females) with a median (range) age of 64 (34-73) treated surgically with endoscopically assisted Achilles tendon reconstruction using a semitendinosus autograft were included. The patients were evaluated at 12 months post-operatively for Achilles tendon Total Rupture Score (ATRS), calf circumference, Achilles Tendon Resting Angle (ATRA), heel-rise height and repetitions together with tendon length determined by ultrasonography, concentric heel-rise power and heel-rise work.
Results: The patients reported a median (range) ATRS of 76 (45-99) out of 100. The median (range) ATRA on the injured side was 60° (49°-75°) compared with 49.5° (40-61°), p < 0.001, on the non-injured side. Eighteen out of 22 patients were able to perform a single-leg heel-rise on the non-injured side. Sixteen patients out of those 18 (89%) were also able to perform a single heel-rise on the injured side. They did, however, perform significantly lower number of repetitions compared with the non-injured side with a median (range) heel-rise repetitions of 11 (2-22) compared with 26 (2-27), (p < 0.001), and a median (range) heel-rise height of 5.5 cm (1.0-11.0 cm) compared with 9.0 cm (5.0-11.5 cm), (p < 0.001). The median calf circumference was 1.5 cm smaller on the injured side, 37.5 cm compared with 39 cm, when medians were compared. The median (range) tendon length of the injured side was 24.8 cm (20-28.2 cm) compared with 22 cm (18.4-24.2 cm), (p < 0.001), on the non-injured side.
Conclusion: The study shows that endoscopically assisted reconstruction using a semitendinosus graft to treat chronic Achilles tendon ruptures and re-ruptures with delayed representation produces a satisfactory outcome. The technique can restore heel-rise height in patients with more distal ruptures or large tendon defects and is therefore a viable technique for Achilles tendon reconstruction.
Level of Evidence: IV.

Establishment of virtual fracture clinic in Princess Royal Hospital Telford: Experience and recommendations during the first 9 months (2022)

Type of publication:
Conference abstract

Author(s):
*Khaleeq T.; *Lancaster P.; *Fakoya K.; *Ferreira P.; *Ahmed U.

Citation:
British Journal of Surgery. Conference: ASiT Surgical Innovation Summit – Future Surgery Show. London United Kingdom. 109(SUPPL 1) (pp i13), 2022. Date of Publication: March 2022.

Abstract:
Introduction: Virtual fracture clinics (VFC) have been shown to be a safe and cost-effective way of managing outpatient referrals to the orthopaedic department. During the coronavirus pandemic there has been a push to reduce unnecessary patient contact whilst maintaining patient safety. Method(s): A protocol was developed by the clinical team on how to manage common musculoskeletal presentations to A&E prior to COVID as part of routine service development. Patients broadly triaged into 4 categories; discharge with advice, referral to VFC, referral to face to face clinic or discussion with on call team. The first 9 months of data were analysed to assess types of injury seen and outcomes. Result(s): In total 2489 patients were referred to VFC from internal and external sources. 734 patients were discharged without follow-up and 182 patients were discharged for physiotherapy review. Only 3 patients required admission. Regarding follow-ups, 431 patients had a virtual follow-up while 1036 of patients required further face to face follow up. 87 patients were triaged into subspecialty clinics. 37 patients were felt to have been referred inappropriately. Conclusion(s): BOA guidelines state all patients must be reviewed within 72 hours of their orthopaedic injury. Implementation of a VFC allows this target to be achieved and at the same time reduce patient contact. Almost half the patients were discharged following VFC review, the remaining patients were followed up. This is especially relevant in the current pandemic where reducing unnecessary trips to hospital will benefit the patient and make the most of the resources available.

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The rise in trauma & orthopaedic trainee-led research and audit collaborative projects in the united kingdom since the start of the COVID-19 pandemic. (2022)

Type of publication:
Conference abstract

Author(s):
*Khaleeq T.; *Kabariti R.; *Ahmed U.

Citation:
British Journal of Surgery. Conference: ASiT Surgical Innovation Summit – Future Surgery Show. London United Kingdom. 109(SUPPL 1) (pp i13), 2022. Date of Publication: March 2022.

Abstract:
Introduction: There has been a significant rise in trainee-led trauma & orthopaedic (T&O) multi-centre research collaborative projects globally. Since the start of the COVID-19 pandemic, more emphasis has been on global collaborative research efforts to tackle important research questions. The aim was to evaluate the number of T&O trainee-led research collaborative projects that took part since the start of the COVID-19 pandemic in the UK. Method(s): A retrospective study that evaluated T&O trainee-led national collaborative projects within the UK since the start of the COVID-19 pandemic lockdown (March 2020 to June 2021). Our exclusion criteria included any regional collaborative projects, projects that were started pre-COVID and projects of other surgical specialities. The number of projects identified was compared to that in 2019. Result(s): In 2019, 0 trainee-led collaborative projects were commenced nationally in the UK. Since the COVID-19 pandemic, we identified 10 trainee-led collaborative trauma & orthopaedic projects with 3 being published so far. The level of evidence ranged between 3 and 4. Conclusion(s): Covid has placed significant challenges across healthcare. One positive aspect that has been noted is the increase in multi-centre trainee-led collaborative projects within the UK. Our study highlights the feasibility of a trainee-led high quality collaborative research projects in the UK, emphasising the growing contribution of trainees towards research. Wide-spread availability of new technological tools suchas social media and Redcap facilitates such projects in terms of recruitment and data collection. We would, therefore, recommend expanding this trainee-led collaborative platform across in Europe and Worldwide.

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Plain film x-ray reporting in orthopaedic patients: A reaudit in a district general hospital (2022)

Type of publication:
Conference abstract

Author(s):
*Khaleeq T.; *Shah Foridi J.; *Reading J.

Citation:
British Journal of Surgery. Conference: ASiT Surgical Innovation Summit – Future Surgery Show. London United Kingdom. 109(SUPPL 1) (pp i13), 2022. Date of Publication: March 2022.

Abstract:
Aim: To assess clinical evaluation of plain film x-rays requested for patients in the orthopaedic department (clinic and ward) Standards: Ionising radiation (medical exposure) regulations irmer 2017 procedure j: recording clinical exposure, national guideline and local guidance is in keeping with irmer and good clinical practice. Method(s): 50 plain films of randomly selected (using random number generator) who had attended new patient fracture clinic and ward. An initial audit was done in June and an reaudit in September. The radiology system, clinical notes and clinic letters were reviewed to obtain the relevant data. Result(s): Audit: 20 films were documented 30 were not documented Reaudit 32 films were documented by referring clinician 18 films were not documented by referring clinician Audit: Clinical evaluation documented 18 Clinical evaluation not documented 32 Reaudit: Clinical evaluation documented – 29 Clinical evaluation not documented – 21 Discussion: Whose responsibility? Radiographs commented on in trauma meetings not documented. New radiographs not commented on in clinic. Limitations – access to more notes from ward. Conclusion(s): As outlined in guidance orthopaedic and fracture clinic plain films should be reported by referring clinician or their team. Currently this is being done 64% of the time, significant improvement was seen. This may have medicolegal consequences as it does not follow GMC guidance for good medical practise. Recommendations: Clinicians to specifically dictate x-ray findings in fracture clinic. Junior staff to take responsibility for documenting x-ray findings as discussed with senior clinicians for trauma patients. Junior staff to review post-op x-rays for all patients and to document.

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Incidence of acute kidney injury in neck of femur fracture patients during the COVID-19 pandemic in Princess Royal Hospital, Telford (2022)

Type of publication:
Conference abstract

Author(s):
Alaguraja P.; Younas W.; Mabeza T.; *Makam A.; *Khaleeq T.; *Reading J

Citation:
British Journal of Surgery. Conference: ASiT Surgical Innovation Summit – Future Surgery Show. London United Kingdom. 109(SUPPL 1) (pp i13), 2022. Date of Publication: March 2022

Abstract:
Aim: Patients undergoing surgical repair of neck-of-femur (NOF) fractures are at higher risk of acute kidney injury (AKI). NICE and BOAST have published guidelines to help prevent the occurrence of AKI, including adequate fluid resuscitation pre- and post-operatively. An audit was conducted during the COVID-19 pandemic to explore whether the department was adhering to NICE guidelines. Method(s): AKI was defined, as per NICE Clinical Knowledge Summaries, as an increase in serum creatinine levels by 26 mumol/L or greater. Data was collected prospectively starting from December 2020 to February 2021 in the Princess Royal Hospital during the COVID-19 pandemic. All patients with NOFs were included and data on sex, age, comorbidities, and type of surgery were collected. Result(s): In total, 32 patients were included in the audit with an average age of 82 years; of these, eleven patients had dynamic hip screws and eighteen patients had hemiarthroplasties. Five patients had chronic kidney disease, six patients had previous myocardial infarctions and thirteen patients had hypertension. Two patients (6.3%) were found to have an AKI post-surgery with increased creatinine levels of 27 and 28 mumol/L. Both had hypertension and underwent hemiarthroplasties. Conclusion(s): Complications such as AKIs are reversible and preventable. Especially during the COVID-19 pandemic such complications can increase morbidity and mortality of patients suffering from NOF leading to longer hospital stays. The low rate of AKI following NOF repair in our Department of Trauma and Orthopaedic is attributable to adherence to NICE and BOAST fluid resuscitation guidelines.

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The British Orthopaedic Surgery Surveillance study: slipped capital femoral epiphysis: the epidemiology and two-year outcomes from a prospective cohort in Great Britain (2022)

Type of publication:
Journal article

Author(s):
Perry DC; Arch B; Appelbe D; Francis P; Craven J; Monsell FP; Williamson P; Knight M; BOSS collaborators (including *Rhee, J of Shrewsbury and Telford Hospital NHS Trust)

Citation:
The Bone & Joint Journal, 2022 Apr; Vol. 104-B (4), pp. 510-518

Abstract:
Aims: The aim of this study was to evaluate the epidemiology and treatment of Perthes' disease of the hip. Methods: This was an anonymized comprehensive cohort study of Perthes' disease, with a nested consented cohort. A total of 143 of 144 hospitals treating children's hip disease in the UK participated over an 18-month period. Cases were cross-checked using a secondary independent reporting network of trainee surgeons to minimize those missing. Clinician-reported outcomes were collected until two years. Patient-reported outcome measures (PROMs) were collected for a subset of participants. Results: Overall, 371 children (396 hips) were newly affected by Perthes' disease arising from 63 hospitals, with a median of two patients (interquartile range 1.0 to 5.5) per hospital. The annual incidence was 2.48 patients (95% confidence interval (CI) 2.20 to 2.76) per 100,000 zero- to 14-year-olds. Of these, 117 hips (36.4%) were treated surgically. There was considerable variation in the treatment strategy, and an optimized decision tree identified joint stiffness and age above eight years as the key determinants for containment surgery. A total of 348 hips (88.5%) had outcomes to two years, of which 227 were in the late reossification stage for which a hip shape outcome (Stulberg grade) was assigned. The independent predictors of a poorer radiological outcome were female sex (odds ratio (OR) 2.27 (95% CI 1.19 to 4.35)), age above six years (OR 2.62 (95% CI (1.30 to 5.28)), and over 50% radiological collapse at inclusion (OR 2.19 (95% CI 0.99 to 4.83)). Surgery had no effect on radiological outcomes (OR 1.03 (95% CI 0.55 to 1.96)). PROMs indicated the marked effect of the disease on the child, which persisted at two years. Conclusion: Despite the frequency of containment surgery, we found no evidence of improved outcomes. There appears to be a sufficient case volume and community equipoise among surgeons to embark on a randomized clinical trial to definitively investigate the effectiveness of containment surgery.

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Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity (2022)

Type of publication:
Journal article

Author(s):
Fallerini C.; Picchiotti N.; Baldassarri M.; Zguro K.; Daga S.; Fava F.; Benetti E.; Amitrano S.; Bruttini M.; Palmieri M.; Croci S.; Lista M.; Beligni G.; Valentino F.; Meloni I.; Tanfoni M.; Minnai F.; Colombo F.; Cabri E.; Fratelli M.; Gabbi C.; Mantovani S.; Frullanti E.; Gori M.; Crawley F.P.; Butler-Laporte G.; Richards B.; Zeberg H.; Lipcsey M.; Hultstrom M.; Ludwig K.U.; Schulte E.C.; Pairo-Castineira E.; Baillie J.K.; Schmidt A.; Frithiof R.; Mari F.; Renieri A.; Furini S.; Montagnani F.; Tumbarello M.; Rancan I.; Fabbiani M.; Rossetti B.; Bergantini L.; D'Alessandro M.; Cameli P.; Bennett D.; Anedda F.; Marcantonio S.; Scolletta S.; Franchi F.; Mazzei M.A.; Guerrini S.; Conticini E.; Cantarini L.; Frediani B.; Tacconi D.; Raffaelli C.S.; Feri M.; Donati A.; Scala R.; Guidelli L.; Spargi G.; Corridi M.; Nencioni C.; Croci L.; Caldarelli G.P.; Spagnesi M.; Romani D.; Piacentini P.; Bandini M.; Desanctis E.; Cappelli S.; Canaccini A.; Verzuri A.; Anemoli V.; Pisani M.; Ognibene A.; Pancrazzi A.; Lorubbio M.; Vaghi M.; Monforte A.D.; Miraglia F.G.; Mondelli M.U.; Girardis M.; Venturelli S.; Busani S.; Cossarizza A.; Antinori A.; Vergori A.; Emiliozzi A.; Rusconi S.; Siano M.; Gabrieli A.; Riva A.; Francisci D.; Schiaroli E.; Paciosi F.; Tommasi A.; Scotton P.G.; Andretta F.; Panese S.; Baratti S.; Scaggiante R.; Gatti F.; Parisi S.G.; Castelli F.; Quiros-Roldan E.; Antoni M.D.; Zanella I.; Monica M.D.; Piscopo C.; Capasso M.; Russo R.; Andolfo I.; Iolascon A.; Fiorentino G.; Carella M.; Castori M.; Aucella F.; Raggi P.; Perna R.; Bassetti M.; Biagio A.D.; Sanguinetti M.; Masucci L.; Guarnaccia A.; Valente S.; Vivo O.D.; Doddato G.; Tita R.; Giliberti A.; Mencarelli M.A.; Rizzo C.L.; Pinto A.M.; Perticaroli V.; Ariani F.; Carriero M.L.; Sarno L.D.; Alaverdian D.; Bargagli E.; Mandala M.; Giorli A.; Salerni L.; Zucchi P.; Parravicini P.; Menatti E.; Trotta T.; Giannattasio F.; Coiro G.; Lena F.; Lacerenza L.G.; Coviello D.A.; Mussini C.; Martinelli E.; Mancarella S.; Tavecchia L.; Belli M.A.; Crotti L.; Parati G.; Sanarico M.; Raimondi F.; Biscarini F.; Stella A.; Rizzi M.; Maggiolo F.; Ripamonti D.; Suardi C.; Bachetti T.; Rovere M.T.L.; Sarzi-Braga S.; Bussotti M.; Capitani K.; Dei S.; Ravaglia S.; Artuso R.; Andreucci E.; Gori G.; Pagliazzi A.; Fiorentini E.; Perrella A.; Bianchi F.; Bergomi P.; Catena E.; Colombo R.; Luchi S.; Morelli G.; Petrocelli P.; Iacopini S.; Modica S.; Baroni S.; Segala F.V.; Menichetti F.; Falcone M.; Tiseo G.; Barbieri C.; Matucci T.; Grassi D.; Ferri C.; Marinangeli F.; Brancati F.; Vincenti A.; Borgo V.; Stefania L.; Lenzi M.; Pietro M.A.D.; Vichi F.; Romanin B.; Attala L.; Costa C.; Gabbuti A.; Roberto M.; Zuccon U.; Vietri L.; Ceri S.; Pinoli P.; Casprini P.; Merla G.; Squeo G.M.; Maffezzoni M.; Bruno R.; Vecchia M.; Colaneri M.; Ludovisi S.; Marincevic-Zuniga Y.; Nordlund J.; Luther T.; Larsson A.; Hanslin K.; Gradin A.; Galien S.; Anderberg S.B.; Rosen J.; Rubertsson S.; Clohisey S.; Horby P.; Millar J.; Knight J.; Montgomery H.; Maslove D.; Ling L.; Nichol A.; Walsh T.; Hinds C.; Semple M.G.; Openshaw P.J.M.; Ho A.; McAuley D.; Ponting C.; Rowan K.; Griffiths F.; Oosthuyzen W.; Meikle J.; Finernan P.; Furniss J.; Mcmaster E.; Law A.; Paterson T.; Wackett T.; Armstrong R.; Murphy L.; Fawkes A.; Coutts A.; Donnelly L.; Gilchrist T.; Hafezi K.; Macgillivray L.; Maclean A.; McCafferty S.; Morrice K.; Weaver J.; Boz C.; Golightly A.; Ward M.; Mal H.; Szoor-McElhinney H.; Hendry R.; Stenhouse A.; Cullum L.; Law D.; Law S.; Law R.; Swets M.; Day N.; Taneski F.; Duncan E.; Zechner M.; Parkinson N.; Klaric L.; Bretherick A.D.; Rawlik K.; Pasko D.; Walker S.; Fourman M.H.; Russell C.D.; Richmond A.; Gountouna E.; Harrison D.; Wang B.; Wu Y.; Meynert A.; Kousathanas A.; Moutsianas L.; Yang Z.; Zhai R.; Zheng C.; Grimes G.; Shih B.; Yang J.; Shen X.; Ponting C.P.; Tenesa A.; Vitart V.; Wilson J.F.; Wood S.; Zak A.; Borra C.; Matharu M.; May P.; Alldis Z.; Mitchelmore O.; Bowles R.; Easthorpe A.; Bibi F.; Lancoma-Malcolm I.; Gurasashvili J.; Pheby J.; Shiel J.; Bolton M.; Patel M.; Zongo O.; Ebano P.; Harding P.; Astin-Chamberlain R.; Choudhury Y.; Cox A.; Kallon D.; Burton M.; Hall R.; Blowes S.; Prime Z.; Biddle J.; Prysyazhna O.; Newman T.; Tierney C.; Kassam J.; Shankar-Hari M.; Ostermann M.; Campos S.; Bociek A.; Lim R.; Grau N.; Jones T.O.; Whitton C.; Marotti M.; Arbane G.; Bonner S.; Hugill K.; Reid J.; Welters I.; Waugh V.; Williams K.; Shaw D.; Fernandez Roman J.; Lopez Martinez M.; Johnson E.; Waite A.; Johnson B.; Hamilton O.; Mulla S.; McPhail M.; Smith J.; Barclay L.; Hope D.; McCulloch C.; McQuillan L.; Clark S.; Singleton J.; Priestley K.; Rea N.; Callaghan M.; Andrew G.; Marshall L.; McKechnie S.; Hutton P.; Bashyal A.; Davidson N.; Summers C.; Polgarova P.; Stroud K.; Pathan N.; Elston K.; Agrawal S.; Battle C.; Newey L.; Rees T.; Harford R.; Brinkworth E.; Williams M.; Murphy C.; White I.; Croft M.; Bandla N.; Gellamucho M.; Tomlinson J.; Turner H.; Hussain I.; Thompson C.; Parker H.; Bradley R.; Griffiths R.; Gill J.; Puxty A.; Cathcart S.; Turner L.; Duffy K.; Puxty K.; Joseph A.; Herdman-Grant R.; Simms R.; Swain A.; Naranjo A.; Crowe R.; Sollesta K.; Loveridge A.; Baptista D.; Morino E.; Davey M.; Golden D.; Moreno Cuesta J.; Haldeos A.; Bakthavatsalam D.; Vincent R.; Elhassan M.; Xavier K.; Ganesan A.; Purohit D.; Abdelrazik M.; Morgan J.; Akeroyd L.; Bano S.; Warren D.; Bromley M.; Sellick K.; Gurr L.; Wilkinson B.; Nagarajan V.; Szedlak P.; Cupitt J.; Stoddard E.; Benham L.; Preston S.; Slawson N.; Bradshaw Z.; Brown J.; Caswell M.; Melling S.; Bamford P.; Faulkner M.; Cawley K.; Jeffrey H.; London E.; Sainsbury H.; Nagra I.; Nasir F.; Dunmore C.; Jones R.; Abraheem A.; Al-Moasseb M.; Girach R.; Brantwood C.; Alexander P.; Bradley-Potts J.; Allen S.; Felton T.; Manna S.; Farnell-Ward S.; Leaver S.; Queiroz J.; Maccacari E.; Dawson D.; Castro Delgado C.; Pepermans Saluzzio R.; Ezeobu O.; Ding L.; Sicat C.; Kanu R.; Durrant G.; Texeira J.; Harrison A.; Samakomva T.; Willis H.; Hopkins B.; Thrasyvoulou L.; Jackson M.; Zaki A.; Tibke C.; Bennett S.; Woodyatt W.; Kent A.; Goodwin E.; Brandwood C.; Clark R.; Smit L.; Rooney K.; Thomson N.; Rodden N.; Hughes E.; McGlynn D.; Clark C.; Clark P.; Abel L.; Sundaram R.; Gemmell L.; Brett M.; Hornsby J.; MacGoey P.; Price R.; Digby B.; O'Neil P.; McConnell P.; Henderson P.; Henderson S.; Sim M.; Kennedy-Hay S.; Rooney L.; Baxter N.; Pogson D.; Rose S.; Daly Z.; Brimfield L.; Phull M.K.; Hussain M.; Pogreban T.; Rosaroso L.; Salciute E.; Grauslyte L.; Wraith E.; MacCallum N.; Bercades G.; Hass I.; Smyth D.; Reyes A.; Martir G.; Clement I.D.; Webster K.; Hays C.; Gulati A.; Hodgson L.; Margarson M.; Gomez R.; Baird Y.; Thirlwall Y.; Folkes L.; Butler A.; Meadows E.; Moore S.; Raynard D.; Fox H.; Riddles L.; King K.; Kimber S.; Hobden G.; McCarthy A.; Cannons V.; Balagosa I.; Chadbourn I.; Gardner A.; Horner D.; McLaughlanv D.; Charles B.; Proudfoot N.; Marsden T.; McMorrow L.; Blackledge B.; Pendlebury J.; Harvey A.; Apetri E.; Basikolo C.; Catlow L.; Doonan R.; Knowles K.; Lee S.; Lomas D.; Lyons C.; Perez J.; Poulaka M.; Slaughter M.; Slevin K.; Thomas V.; Walker D.; Harris J.; Drummond A.; Tully R.; Dearden J.; Philbin J.; Munt S.; Rishton C.; O'Connor G.; Mulcahy M.; Dobson E.; Cuttler J.; Edward M.; Sloan B.; Buckley S.; Brooke H.; Smithson E.; Charlesworth R.; Sandu R.; Thirumaran M.; Wagstaff V.; Cebrian Suarez J.; Kaliappan A.; Vertue M.; Riches J.; Solesbury A.; Kittridge L.; Forsey M.; Maloney G.; Cole J.; Davies M.; Davies R.; Hill H.; Thomas E.; Duffin D.; Player B.; Radhakrishnan J.; Gibson S.; Lyle A.; McNeela F.; Patel B.; Gummadi M.; Sloane G.; Dormand N.; Salmi S.; Farzad Z.; Cristiano D.; Liyanage K.; Thwaites V.; Varghese M.; Meredith M.; Mills G.; Willson J.; Harrington K.; Lenagh B.; Cawthron K.; Masuko S.; Raithatha A.; Bauchmuller K.; Ahmad N.; Barker J.; Jackson Y.; Kibutu F.; Bird S.; Watson G.; Martin J.; Bevan E.; Wrey Brown C.; Trodd D.; English K.; Bell G.; Wilcox L.; Katary A.; Gopal S.; Lake V.; Harris N.; Metherell S.; Radford E.; Scriven J.; Moore F.; Bancroft H.; Daglish J.; Sangombe M.; Carmody M.; Rhodes J.; Bellamy M.; Garg A.; Kuravi A.; Virgilio E.; Ranga P.; Butler J.; Botfield L.; Dexter C.; Fletcher J.; Shanmugasundaram P.; Hambrook G.; Burn I.; Manso K.; Thornton D.; Tebbutt J.; Penn R.; Hulme J.; Hussain S.; Maqsood Z.; Joseph S.; Colley J.; Hayes A.; Ahmed C.; Haque R.; Clamp S.; Kumar R.; Purewal M.; Baines B.; Frise M.; Jacques N.; Coles H.; Caterson J.; Gurung Rai S.; Brunton M.; Tilney E.; Keating L.; Walden A.; Antcliffe D.; Gordon A.; Templeton M.; Rojo R.; Banach D.; Sousa Arias S.; Fernandez Z.; Coghlan P.; Williams D.; Jardine C.; Bewley J.; Sweet K.; Grimmer L.; Johnson R.; Garland Z.; Gumbrill B.; Ortiz-Ruiz de Gordoa L.; Peasgood E.; Tridente A.; Shuker K.; Greer S.; Lynch C.; Turner K.; Singh J.; Sera Howe G.; Paul P.; Gill M.; Wynter I.; Ratnam V.; Shelton S.; Naisbitt J.; Melville J.; Baruah R.; Morrison S.; McGregor A.; Mpelembue M.; Srikaran S.; Dennis C.; Sukha A.; Williams A.; Verlande M.; Holding K.; Riches K.; Downes C.; Swan C.; Rostron A.; Roy A.; Woods L.; Cornell S.; Wakinshaw F.; Creagh-Brown B.; Blackman H.; Salberg A.; Smith E.; Donlon S.; Mtuwa S.; Michalak-Glinska N.; Stone S.; Beazley C.; Pristopan V.; Nikitas N.; Lankester L.; Wells C.; Raj A.S.; Fletcher K.; Khade R.; Tsinaslanidis G.; McMahon M.; Fowler S.; Coventry T.; Stewart R.; Wren L.; Mwaura E.; Mew L.; Rose A.; Scaletta D.; Williams F.; Inweregbu K.; Nicholson A.; Lancaster N.; Cunningham M.; Daniels A.; Harrison L.; Hope S.; Jones S.; Crew A.; Wray G.; Matthews J.; Crawley R.; Carter J.; Birkinshaw I.; Ingham J.; Scott Z.; Howard K.; Joy R.; Roche S.; Purvis S.; Morrison A.; Strachan D.; Clements S.; Black K.; Parmar C.; Altabaibeh A.; Mostoles L.; Gilbert K.; Ma L.; Alvaro A.; Thomas M.; Faulkner B.; Worner R.; Hayes K.; Gendall E.; Blakemore H.; Borislavova B.; Goff E.; Vuylsteke A.; Mwaura L.; Zamikula J.; Garner L.; Mitchell A.; Mepham S.; Cagova L.; Fofano A.; Holcombe H.; Praman K.; Szakmany T.; Heron A.E.; Cherian S.; Cutler S.; Roynon-Reed A.; Randell G.; Convery K.; Stammers K.; Fottrell-Gould D.; Hudig L.; Keshetprice J.; Peters M.; O'Neill L.; Ray S.; Belfield H.; McHugh T.; Jones G.; Akinkugbe O.; Tomas A.; Abaleke E.; Beech E.; Meghari H.; Yussuf S.; Bamford A.; Hairsine B.; Dooks E.; Farquhar F.; Packham S.; Bates H.; McParland C.; Armstrong L.; Kaye C.; Allan A.; Medhora J.; Liew J.; Botello A.; Anderson F.; Cusack R.; Golding H.; Prager K.; Williams T.; Leggett S.; Golder K.; Male M.; Jones O.; Criste K.; Marani M.; Anumakonda V.; Amin V.; Karthik K.; Kausar R.; Anastasescu E.; Reid K.; Jacqui M.; Hormis A.; Walker R.; Collier D.; Duncan T.; Uriel A.; Ustianowski A.; T-Michael H.; Bruce M.; Connolly K.; Smith K.; Partridge R.; Griffin D.; McDonald M.; Muchenje N.; Martin D.; Filipe H.; Eastgate C.; Jackson C.; Gratrix A.; Foster L.; Martinson V.; Stones E.; Abernathy C.; Parkinson P.; Reed A.; Prendergast C.; Rogers P.; Woodruff M.; Shokkar R.; Kaul S.; Barron A.; Collins C.; Beavis S.; Whileman A.; Dale K.; Hawes J.; Pritchard K.; Gascoyne R.; Stevenson L.; Jha R.; Lim L.; Krishnamurthy V.; Parker R.; Turner-Bone I.; Wilding L.; Reddy A.; Whiteley S.; Wilby E.; Howcroft C.; Aspinwall A.; Charlton S.; Ogg B.; Menzies D.; Pugh R.; Allan E.; Lean R.; Davies F.; Easton J.; Qiu X.; Kumar S.; Darlington K.; Houston G.; O'Brien P.; Geary T.; Allan J.; Meikle A.; Hughes G.; Balasubramaniam M.; Latham S.; McKenna E.; Flanagan R.; Sathe S.; Davies E.; Roche L.; Chablani M.; Kirkby A.; Netherton K.; Archer S.; Yates B.; Ashbrook-Raby C.; Cole S.; Cabrelli L.; Chapman S.; Casey M.; Austin P.; Hutcheon A.; Whyte C.; Almaden-Boyle C.; Pattison N.; Cruz C.; Vochin A.; Kent H.; Murdoch S.; David B.; Penacerrada M.; Lubimbi G.; Bastion V.; Wulandari R.; Valentine J.; Clarke D.; Serrano-Ruiz A.; Hierons S.; Ramos L.; Demetriou C.; Mitchard S.; White K.; White N.; Pitts S.; Branney D.; Frankham J.; Watters M.; Langton H.; Prout R.; Page V.; Varghes T.; Kay A.; Potts K.; Birt M.; Kent M.; Wilkinson A.; Jude E.; Turner V.; Savill H.; McCormick J.; Clark M.; Coulding M.; Siddiqui S.; Mercer O.; Rehman H.; Potla D.; *Capps N.; *Donaldson D.; *Jones J.; *Button H.; *Martin T.; *Hard K.; *Agasou A.; *Tonks L.; *Arden T.; *Boyle P.; *Carnahan M.; Strickley J.; Adams C.; Childs D.; *Rikunenko R.; *Leigh M.; *Breekes M.; *Wilcox R.; *Bowes A.; *Tiveran H.; *Hurford F.; *Summers J.; *Carter A.; *Hussain Y.; *Ting L.; *Javaid A.; *Motherwell N.; *Moore H.; *Millward H.; *Jose S.; *Schunki N.; *Noakes A.; *Clulow C.; Sadera G.; Jacob R.; Jones C.; Blunt M.; Coton Z.; Curgenven H.; Mohamed Ally S.; Beaumont K.; Elsaadany M.; Fernandes K.; Ali Mohamed Ali I.; Rangarajan H.; Sarathy V.; Selvanayagam S.; Vedage D.; White M.; Smith M.; Truman N.; Chukkambotla S.; Keith S.; Cockerill-Taylor J.; Ryan-Smith J.; Bolton R.; Springle P.; Dykes J.; Thomas J.; Khan M.; Hijazi M.T.; Massey E.; Croston G.; Reschreiter H.; Camsooksai J.; Patch S.; Jenkins S.; Humphrey C.; Wadams B.; Bhatia N.; Msiska M.; Adanini O.; Attwood B.; Parsons P.; Tatham K.; Jhanji S.; Black E.; Dela Rosa A.; Howle R.; Thomas B.; Bemand T.; Raobaikady R.; Saha R.; Staines N.; Daniel A.; Finn J.; Hutter J.; Doble P.; Shovelton C.; Pawley C.; Kannan T.; Hill M.; Combes E.; Monnery S.; Joefield T.; Popescu M.; Thankachen M.; Oblak M.; Little J.; McIvor S.; Brady A.; Whittle H.; Prady H.; Chan R.; Ahmed A.; Morris A.; Gibson C.; Gordon E.; Keenan S.; Quinn H.; Benyon S.; Marriott S.; Zitter L.; Park L.; Baines K.; Lyons M.; Holland M.; Keenan N.; Young M.; Garrioch S.; Dawson J.; Tolson M.; Scholefield B.; Bi R.; Richardson N.; Schumacher N.; Cosier T.; Millen G.; Higham A.; Simpson K.; Turki S.; Allen L.; Crisp N.; Hazleton T.; Knight A.; Deery J.; Price C.; Turney S.; Tilbey S.; Beranova E.; Wright D.; Georg L.; Twiss S.; Cowton A.; Wadd S.; Postlethwaite K.; Gondo P.; Masunda B.; Kayani A.; Hadebe B.; Whiteside J.; Campbell R.; Clarke N.; Donnison P.; Trim F.; Leadbitter I.; O'Sullivan S.; Purewal B.; Bell S.; Rivers V.; O'Leary R.; Collins E.; Anderson S.; Hammerton K.; Andrews E.; Burns K.; Edmond I.; Salutous D.; Todd A.; Donnachie J.; Turner P.; Prentice L.; Symon L.; Runciman N.; Auld F.; Halkes M.; Mercer P.; Thornton L.; Debreceni G.; Wilkins J.; Crickmore V.; Subramanian G.; Marshall R.; Jennings C.; Latif M.; Bunni L.; Spivey M.; Bean S.; Burt K.; Linnett V.; Ritzema J.; Sanderson A.; Bokhari M.; Kapoor R.; Loader D.; Ayers A.; Harrison W.; North J.; Belagodu Z.; Parasomthy R.; Olufuwa O.; Gherman A.; Fuller B.; Stuart C.; Kelsall O.; Davis C.; Wild L.; Wood H.; Thrush J.; Durie A.; Austin K.; Archer K.; Anderson P.; Vigurs C.; Thorpe C.; Thomas A.; Knights E.; Boyle N.; Price A.; Kubisz-Pudelko A.; Wood D.; Lewis A.; Board S.; Pippard L.; Perry J.; Beesley K.; Rattray A.; Lee E.; Lennon L.; Douglas K.; Bell D.; Boyle R.; Nauman Akhtar M.; Dent K.; Potoczna D.; Pearson S.; Horsley E.; Spencer S.; Phillips C.; Mullan D.; Skinner D.; Gaylard J.; Ortiz-Ruizdegordoa L.; Barber R.; Hewitt C.; Hilldrith A.; Shepardson S.; Wills M.; Jackson-Lawrence K.; Gupta A.; Easthope A.; Timlick E.; Gorman C.; Otaha I.; Gales A.; Coetzee S.; Raj M.; Peiu M.; Parris V.; Quaid S.; Watson E.; Elliott K.; Mallinson J.; Chandler B.; Turnbull A.; Quinn A.; Finch C.; Holl C.; Cooper J.; Evans A.; Collins A.; Treus Gude E.; Love N.; van Koutrik L.; Hunt J.; Kaye D.; Fisher E.; Brayne A.; Tuckey V.; Jackson P.; Parkin J.; Brealey D.; Raith E.; Tariq A.; Houlden H.; Tucci A.; Hardy J.; Moncur E.; Highgate J.; Cowley A.; Mitra A.; Stead R.; Behan T.; Burnett C.; Newton M.; Heeney E.; Pollard R.; Hatton J.; Patel A.; Kasipandian V.; Allibone S.; Genetu R.M.; Otahal I.; O'Brien L.; Omar Z.; Perkins E.; Davies K.; Tetla D.; Pothecary C.; Deacon B.; Shelley B.; Irvine V.; Williams S.; Williams P.; Birch J.; Goodsell J.; Tutton R.; Bough L.; Winter-Goodwin B.; Kitson R.; Pinnell J.; Wilson A.; Nortcliffe T.; Wood T.; Home M.; Holdroyd K.; Robinson M.; Shaw R.; Greig J.; Brady M.; Haigh A.; Matupe L.; Usher M.; Mellor S.; Dale S.; Gledhill L.; Shaw L.; Turner G.; Kelly D.; Anwar B.; Riley H.; Sturgeon H.; Ali A.; Thomis L.; Melia D.; Dance A.; Hanson K.; Humphreys S.; Frost I.; Gopal V.; Godden J.; Holden A.; Swann S.; Clapham M.; Poultney U.; Harper R.; Rice P.; Khaliq W.; Reece-Anthony R.; Gurung B.; Moultrie S.; Odam M.; Mayer A.; Bellini A.; Pickard A.; Bryant J.; Roe N.; Sowter J.; Butcher D.; Lang K.; Taylor J.; Barry P.; Hobrok M.; Tench H.; Wolf-Roberts R.; McGuinness H.; Loosley R.; Hawcutt D.; Rad L.; O'Malley L.; Saunderson P.; Seddon G.; Anderson T.; Rogers N.; Ruddy J.; Harkins M.; Taylor M.; Beith C.; McAlpine A.; Ferguson L.; Grant P.; MacFadyen S.; McLaughlin M.; Baird T.; Rundell S.; Glass L.; Welsh B.; Hamill R.; Fisher F.; Smith T.; Gregory J.; Brown A.; Rolker S.; Nothen M.M.; Fazaal J.; Keitel V.; Jensen B.; Feldt T.; Knopp L.; Schroder J.; Maj C.; Brand F.; Berger M.M.; Brenner T.; Hinney A.; Witzke O.; Bals R.; Herr C.; Ludwig N.; Walter J.; Schneider J.; Erber J.; Spinner C.D.; Wendtner C.M.; Winter C.; Protzer U.; Casadei N.; Ossowski S.; Motameny S.; Riess O.H.; Kwasniewski M.; Korotko U.; Chwialkowska K.; Niemira M.; Jaroszewicz J.; Sobala-Szczygiel B.; Puzanowska B.; Parfieniuk-Kowerda A.; Martonik D.; Moniuszko-Malinowska A.; Pancewicz S.; Zarebska-Michaluk D.; Simon K.; Pazgan-Simon M.; Mozer-Lisewska I.; Bura M.; Adamek A.; Tomasiewicz K.; Pawlowska M.; Piekarska A.; Berkan-Kawinska A.; Horban A.; Kowalska J.; Podlasin R.; Wasilewski P.; Azzadin A.; Czuczwar M.; Czaban S.; Olszewski P.; Bogocz J.; Ochab M.; Kruk A.; Uszok S.; Bielska A.; Szalkowska A.; Raczkowska J.; Sokolowska G.; Chorostowska-Wynimko J.; Jezela-Stanek A.; Rozy A.; Lechowicz U.; Polowianiuk U.; Grubczak K.; Starosz A.; Eljaszewicz A.; Izdebska W.; Kretowski A.; Flisiak R.; Moniuszko M.; Abedalthagafi M.; Alaamery M.; Massadeh S.; Fawzy M.; AlBardis H.; Aljawini N.; Alsuwailm M.; Almalki F.; Mangul S.; Jung J.; Mbarek H.; Saad C.; Al-Sarraj Y.; Al-Muftah W.; Badji R.; Thani A.A.; Ismail S.I.;

Citation:
Human Genetics. 2022, Vol 141(1) (pp 147-173)

Abstract:
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.

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Creating and employing an admission bloods based diagnostic aide for COVID-19 to assist cohort-based isolation strategies (2022)

Type of publication:
Conference abstract

Author(s):
*Baker J.; *Day S.; *Marsh A.

Citation:
Emergency Medicine Journal. Conference: Royal College of Emergency Medicine Annual Scientific Conference, RCEM 2022. Belfast United Kingdom. 39(3) (pp 259-260), 2022. Date of Publication: March 2022.

Abstract:
Aims/Objectives/Background In the COVID-19 pandemic the Shrewsbury and Telford Hospital NHS Trust has isolated suspected cases in high and low suspicion cohort bays to reduce nosocomial infection. Before rapid PCR swabs were in routine use, we sought tools to aide identifying COVID-19 positive patients. Methods/Design We collected data from two cohorts in April and June 2020 totalling 317 patients, with positivity rates of 33% and 5% respectively. We retrospectively correlated neutrophil count, lymphocyte count, LDH and AST to positive and negative swab results. Predictive value of COVID-19 positivity was assessed via their receiver operator characteristic. Areas under the curve were as follows: Neutrophils 0.75, lymphocytes 0.64, combined neutrophil and lymphocyte count 0.82, AST 0.65 and LDH 0.7. We developed a diagnostic aide to assist in allocation of high and low suspicion based on parameters for neutrophil count, lymphocyte count and LDH, each of which was assigned red (higher probability) or green (lower probability) in a 'traffic light' system. Combined and applied retrospectively to 252 patients with suspected COVID-19, with a positivity prevalence of 5%, three green values generated a negative predictive value for COVID-19 of 100%, two greens 98% and three reds a positive predictive value for COVID-19 of 44%. Results/Conclusions This diagnostic aide was applied from August 2020 within the Trust Emergency Departments and Acute Medical Units to aide cohort decisions. A retrospective application to all 213 patients with positive swabs admitted from August to November 2020 demonstrated that 69% were highlighted as at least two 'red lights' and only 1.4% were erroneously highlighted as three 'green lights'. The aide is an example of a rapidly developed evidence based tool and, particularly if updated with data from other centres, could be widely employed in low-resource healthcare settings. (Figure Presented).