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).

The changing landscape for the management of patients with neovascular AMD: brolucizumab in clinical practice (2022)

Type of publication:
Journal article

Author(s):
Pearce I; Amoaku W; Bailey C; Downey L; Gale R; Ghanchi F; Hamilton R; Mahmood S; Menon G; *Nosek J; Talks J; Yang Y

Citation:
Eye. 36(9) (pp 1725-1734), 2022. Date of Publication: September 2022.

Abstract:
Untreated neovascular age-related macular degeneration (nAMD) can lead to severe and permanent visual impairment. The chronic nature of the disease can have a significant impact on patients' quality of life and an economic and time burden on medical retina (MR) services, with the care need outweighing the growth of resources that clinical services can access. The introduction of a new treatment into clinical services can be challenging, especially for services that are already under capacity constraints. Guidance for practical implementation is therefore helpful. Roundtable meetings, facilitated by Novartis UK, between a working group of MR experts with experience of leading and managing NHS retinal services in the intravitreal era were conducted between 2020 and 2021. These meetings explored various aspects and challenges of introducing a new anti-vascular endothelial growth factor (VEGF) therapy to the UK medical retina services. Provision of clear expert recommendations and practical guidance nationally, that can be adapted locally as required to support clinicians and healthcare professionals (HCPs), is valuable in supporting the introduction of a new anti-VEGF therapy within the NHS environment. The experts provide ophthalmologic HCPs with a collation of insights and recommendations to support the introduction and delivery of brolucizumab in their local service in the face of current and projected growth in demand for retina care.

Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant (2022)

Type of publication:
Journal article

Author(s):
*Parikh S; *Pettit L; *AbdelGadir H

Citation:
BMJ Case Reports, 2022 Mar 22; Vol. 15

Abstract:
Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant – a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

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A Systematic Review of Long-Distance Triathlon Musculoskeletal Injuries (2022)

Type of publication:Journal article

Author(s):Rhind JH; Dass D; Barnett A; *Carmont M

Citation:Journal of Human Kinetics 2022 Feb 10; Vol. 81, pp. 123-134.

Abstract:The distribution of injuries affecting long-distance triathletes is yet to be fully understood. A systematic review was performed of the clinical literature to determine the epidemiology of musculoskeletal injuries affecting long-distance triathletes. Searched databases in Feb 2020 were PubMed, Medline, EMBASE, EMCARE, and CINHAL databases. Published observational research articles related to the incidence or prevalence of musculoskeletal injuries in long-distance triathletes (competing at "Ironman" full distance or greater), written in the English language and not restricted by age or gender or date were eligible. Of the 975 studies identified on the initial search, six studies met the inclusion criteria for analysis. The mean age (SD) of the long-distance triathletes in these studies was 35.1 (2.7) and the range was 21-68 years. Overuse injuries were most frequent with the incidence range of 37-91%, and acute injury incidence range was 24-27%. The knee and spine were the most frequent location of injury. Running and cycling were the most frequently affected disciplines. Elite athletes had a lower incidence of overuse injury (37%). The highest acute injury incidence (27%) was recorded in non-elite athletes. The quality of the studies was relatively poor with only one study satisfying >50% of the quality assessment tool questions and only two studies were prospective, the rest were retrospective cross-sectional studies. Overall, there is a lack of literature reporting on musculoskeletal injuries in long-distance triathletes. Overuse injuries, particularly in the knee, are the most frequently reported, running and cycling are the most frequent disciplines associated. Long-distance triathletes may have a lower incidence of both overuse and acute injuries.

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Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial (2022)

Type of publication:Randomised controlled trial

Author(s):Dearnaley, David; Hinder, Victoria; Hijab, Adham; Horan, Gail; *Srihari, Narayanan; Rich, Philip; Houston, J Graeme; Henry, Ann M; Gibbs, Stephanie; Venkitaraman, Ram; Cruickshank, Clare; Hassan, Shama; Miners, Alec; Mason, Malcolm; Pedley, Ian; Payne, Heather; Brock, Susannah; Wade, Robert; Robinson, Angus; Din, Omar; Lees, Kathryn; Graham, John; Worlding, Jane; Murray, Julia; Parker, Chris; Griffin, Clare; Sohaib, Aslam; Hall, Emma; PROMPTS investigators

Citation:
The Lancet Oncology. 23(4) (pp 501-513), 2022. Date of Publication: April 2022.

Abstract:BACKGROUND Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. METHODS We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0-2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. FINDINGS Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. INTERPRETATION Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. FUNDING Cancer Research UK.

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The global level of harm among surgical professionals during the COVID-19 pandemic: A multinational cross-sectional cohort study (2022)

Type of publication:Journal article

Author(s):Abouelazayem, Mohamed; Viswanath, Yirupaiahgari K S; Bangash, Ali Haider; Herrera Kok, Johnn Henry; Cheruvu, Chandra; Parmar, Chetan; Atici, Semra Demirli; Yang, Wah; Galanis, Michail; Di Maggio, Francesco; Isik, Arda; *Bandyopadhyay, Samik Kumar

Citation:Surgery; Mar 2022 [epub ahead of print]

Abstract:BACKGROUND Health care workers, including surgical professionals, experienced psychological burnout and physical harm during the coronavirus 2019 pandemic. This global survey investigated the coronavirus 2019 pandemic impact on psychological and physical health.
METHODS We conducted a global cross-sectional survey between February 18, 2021 and March 13, 2021. The primary outcome was to assess the psychological burnout, fulfillment, and self-reported physical level of harm. A validated Stanford Professional Fulfilment Index score with a self-reported physical level of harm was employed. We used a practical overall composite level ofharm score to calculate the level of harm gradient 1-4, combining psychological burnout with self-reported physical level of harm score.
RESULTS A total of 545 participants from 66 countries participated. The final analysis included 520 (95.4%) surgical professionals barring medical students. Most of the participants (81.3%)were professionally unfulfilled. The psychological burnout was evident in 57.7% and was significantly common in those <50 years (P = .002) and those working in the public sector (P = .005). Approximately 41.7% of respondents showed changes in the physical health with self-remedy and no impact on work, whereas 14.9% reported changes to their physical health with <2 weeks off work, and 10.1% reported changes in physical health requiring >2 weeks off work. Severe harm (level of harm 4) was detected in 10.6%, whereas moderate harm (level of harm 3) affected 40.2% of the participants. Low and no harm (level of harm 2 and level of harm 1) represented 27.5% and 21.7%, respectively. CONCLUSION Our study showed that high levels of psychological burnout, professional unfulfillment, work exhaustion, and severe level of harm was more frequent in younger professionals working in the public sector. The findings correlated with a high level of harm in surgical professionals impacting surgical services.

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Learning curves in minimally invasive pancreatic surgery: a systematic review (2022)

Type of publication:Systematic Review

Author(s):Fung, Gayle; Sha, Menazir; Kunduzi, Basir; Froghi, Farid; *Rehman, Saad; Froghi, Saied

Citation:
Langenbeck's Archives of Surgery. 407(6) (pp 2217-2232), 2022. Date of Publication: September 2022.

Abstract:BACKGROUND The learning curve of new surgical procedures has implications for the education, evaluation and subsequent adoption. There is currently no standardised surgical training for those willing to make their first attempts at minimally invasive pancreatic surgery. This study aims to ascertain the learning curve in minimally invasive pancreatic surgery.
METHODS A systematic search of PubMed, Embase and Web of Science was performed up to March 2021. Studies investigating the number of cases needed to achieve author-declared competency in minimally invasive pancreatic surgery were included.
RESULTS In total, 31 original studies fulfilled the inclusion criteria with 2682 patient outcomes being analysed. From these studies, the median learning curve for distal pancreatectomy was reported to have been achieved in 17 cases (10-30) and 23.5 cases (7-40) for laparoscopic and robotic approach respectively. The median learning curve for pancreaticoduodenectomy was reported to have been achieved at 30 cases (4-60) and 36.5 cases (20-80) for a laparoscopic and robotic approach respectively. Mean operative times and estimated blood loss improved in all four surgical procedural groups. Heterogeneity was demonstrated when factoring in the level of surgeon's experience and patient's demographic.
CONCLUSIONS There is currently no gold standard in the evaluation of a learning curve. As a result, derivations are difficult to utilise clinically. Existing literature can serve as a guide for current trainees. More work needs to be done to standardise learning curve assessment in a patient-centred manner.

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COACH: Challenging osteoarthritis and changing health (2021)

Type of publication:Conference abstract

Author(s):*Haines-Eynon A.

Citation:Physiotherapy, 2021. Conference: Virtual Physiotherapy UK 2020 Conference. Virtual, Online. 113(Supplement 1) (pp e52-e53)

Abstract:Purpose: To develop, implement and evaluate an integrated rehabilitation programme for patients with hip and knee osteoarthritis (OA). To encourage behavioural changes by using social prescribing to facilitate longer-term management. Method(s): Patients with OA of the hip and/or knee were eligible for the class. An attempt was made to include as many patients as possible even with comorbidities. Any patients with any cardiac or respiratory conditions were still eligible provided they were able to manage any acute changes to their condition. Patients were assessed by a physiotherapist following a referral from a GP, ESP or consultant who completed an induction including 4 outcome measures; MSK-HQ, numeric rating scale (NRS), 30-s sit to stand and 4 x 10 m walk test. Patients took part in a 6-week programme consisting of 6 weekly 1 h sessions. Each session included a targeted strengthening circuit and a changing education presentation designed to help people improve their understanding of the condition. The final session which focused around longer term self management was attended by the Healthy Lifestyles Team to educate patients on available services within the local community. At the end of the final session all outcome measures were repeated and patients were given a patient satisfaction questionnaire. On completion of the class patients were given the opportunity to continue with their exercise programme in the hospital gym for a further period of time or encouraged to continue with their exercises in their local gym. They were referred back to their physiotherapist if they were still not able to manage their symptoms. Result(s): One hundred and twenty-three patients started the class, three of these were referred back to their physiotherapist as they were unable to engage in the class environment and a further 17 did not complete the course after the initial session. At least 75% of patients had repeat scores greater than or equal to their initial results on all outcome measures. The minimal clinically important improvement (MCII) value was achieved in 50.6% of patients in the MSK-HQ, 31.6% in the 4 x 10 m walk test, 36.7% in the NRS and 46.5% in the 30 s sit to stand test. Conclusion(s): The results demonstrate an important improvement to patient's pain and function following six exercise class and educational sessions. A wide inclusion criterion with patients who had multiple comorbidities meant these outcomes are more representative of the population and are more generalizable. Giving patients a starting point and a seamless approach from a hospital environment to self-management makes it more likely that patients will continue with a healthy lifestyle reducing the need for recurring visits to healthcare providers. Impact: The class had capacity for up to 12 patients allowing patients more treatment time compared to a routine 20 min follow up appointment. Also by avoiding 1:1 physiotherapy appointments the strain on acute services and its associated costs were reduced. This programme Identifies a further effective treatment option for patients with hip and knee OA. Funding acknowledgements: No funding was required for this study.