106 research outputs found
Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 19/05/2023
- Field of study
Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis
Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers
- Author
- Publication venue
- American Society for Clinical Investigation
- Publication date
- 21/03/2024
- Field of study
Novel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections. We applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modelling and network correlation analyses identified 118 differentially expressed proteins, significant through three complementary analytical pipelines. Candidate biomarkers were subsequently analysed in two validation cohorts of differing ethnicity using antibody-based proximity extension assays. TB-specific host biomarkers were confirmed. A six-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14 and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts. This biomarker panel exceeds the World Health Organisation Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic
Malaria elimination challenges in Mesoamerica: evidence of submicroscopic malaria reservoirs in Guatemala
- Author
- A Harris
- A Vallejo
- Adolfo Miranda
- AF Vallejo
- Alvaro Alvarez
- Andres F. Vallejo
- C Cotter
- C Luxemburger
- DD Laishram
- FP Alves
- HJ Sturrock
- JM Cohen
- JT Lin
- Juliana Henao
- Julianh Perez
- K Mendis
- LC Okell
- M da Silva-Nunes
- M Imwong
- Myriam Arévalo-Herrera
- O Branch
- PG Shute
- RE Coleman
- S Herrera
- S Herrera
- Shirley Evelyn Lennon
- Sócrates Herrera
- T Bousema
- WHO
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Evaluating the Immune Response in Treatment-Naive Hospitalised Patients With Influenza and COVID-19
- Author
- Publication venue
- 'Frontiers Media SA'
- Publication date
- 19/05/2022
- Field of study
The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body’s immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival
High prevalence of sub-microscopic infections in Colombia
- Author
- AF Vallejo
- Andres F Vallejo
- B Faye
- B Roshanravan
- C Cotter
- C Souza
- DL Doolan
- FP Alves
- H Hopkins
- I Harris
- Instituto Nacional de Salud
- J Alves
- J Baird
- JF Mosha
- JT Bousema
- Juan Pablo Quintero
- Julio Padilla
- KA Lindblade
- KM VanBuskirk
- L Golassa
- LC Okell
- M Arevalo-Herrera
- MM Rodrigues
- Myriam Arévalo-Herrera
- PA Harris
- Pablo E Chaparro
- PL Alonso
- RE Coleman
- RW Snow
- S Herrera
- SD Polley
- Sócrates Herrera
- TN Sousa
- WHO
- Yoldy Benavides
- ZM Cucunuba
- ZM Cucunuba
- Álvaro Álvarez
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Comparative chemistry and insect antifeedant effects of conventional (Clevenger and Soxhlet) and supercritical extracts (CO2) of two Lavandula luisieri populations
- Author
- Abdelgaleil
- Alzogaray
- Ana M. Mainar
- Ando
- Andres
- Antonious
- Azucena González-Coloma
- Baldovini
- Birkett
- Burgueño-Tapia
- Castillo
- Eisner
- Farghaly
- Figadere
- García-Vallejo
- González-Coloma
- González-Coloma
- Jesus Sanz
- Jesús Burillo
- José S. Urieta
- Kamatou
- Kim
- Kim
- Kim
- Koul
- Langa
- Langenheim
- Lavoine-Hanneguelle
- Lee
- Luis F. Julio
- Luis Martín
- Martín
- Mbata
- Mc Lafferty
- Michaelakis
- Nukenine
- Piesik
- Reisenman
- Rivas-Martínez
- Rivas-Martínez
- Rivas-Martínez
- Roach
- Rodilla
- Rubén Muñoz
- Samarasekera
- Santana
- Sanz
- Savelev
- Tarelli
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry
- Author
- Abban D. W.
- Abdul N.
- Abud A. M.
- Adams F.
- Addala S.
- Adragao P.
- Ageno W.
- Aggarwal R.
- Agosti S.
- Agostoni P.
- Aguilar F.
- Aguinaga L.
- Ahmed J.
- Aiello A.
- Ainsworth P.
- Aiub J. R.
- Al-Dallow R.
- Alderson L.
- Alexopoulos D.
- Aliyar P.
- Almeida L. F.
- Alonso D.
- Alvaro F.
- Amado J.
- Amara W.
- Amelot M.
- Amjadi N.
- Ammirati F.
- Andrade M.
- Andrawis N.
- Andres H.
- Annoni G.
- Ansalone G.
- Antero C.
- Ariani M. K.
- Arias J. C.
- Armero S.
- Arora C.
- Asensi J. O.
- Aslam M. S.
- Asselman M.
- Audouin P.
- Augenbraun C.
- Ayala C.
- Aydin S.
- Aydin S.
- Ayryanova I.
- Aziz E.
- Backes L. M.
- Badings E.
- Bagni E.
- Baker S. H.
- Bala R.
- Baldicortada A. J. B.
- Banerjeebrunschwig S. C.
- Bank A.
- Barrbullinga C. J.
- Bartlettcabrera M. J. W.
- Basic KesCaccavo V. A.
- Baulacai G. S.
- Behrenscaine S. S.
- Bellcalo A. L.
- Benedetti R.
- Benhalimacandeias B. R.
- Berg J. M.
- Bergler-Klein J.
- Berneaucapucci J. -B. A.
- Bernsteincaputo R. A. R.
- Berrospirizo P. T. C.
- Berti S.
- Best E.
- Bettencourtcarolei P. A.
- Betzucarreno R. S.
- Bhagwatcarvalho R. P.
- Bhatta L.
- Biscionecasu F. G.
- Bisignani C.
- Bisignani G.
- Blackcayla T. G.
- Blochcelentano M. J. A.
- Bloom S.
- Blumberg E.
- Bo M
- Bodes R. S.
- Bohmer E.
- Bollmann A.
- Bongiorni M. G.
- Boriani G.
- Bott J.
- Bottacchi E.
- Bradman D.
- Brautigam D.
- Breton N.
- Briones I. R.
- Brkljacic D. D.
- Brouwers P. J. A. M.
- Browne K.
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- Buhl A.
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- Calvi V.
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- Cardona F.
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- Chumakova G.
- Cislowski D. J.
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- Coodley G.
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- Zukerman L. S.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo
- Author
- Abac A. G.
- Abbott R.
- Abe H.
- Acernese F.
- Ackley K.
- Adamcewicz C.
- Adhicary S.
- Adhikari N.
- Adhikari R. X.
- Adkins V. K.
- Adya V. B.
- Affeldt C.
- Agarwal D.
- Agathos M.
- Aguiar O. D.
- Aguilar I.
- Aiello L.
- Ain A.
- Ajith P.
- Akutsu T.
- Al-Jodah A.
- Albanesi S.
- Alfaidi R. A.
- Allocca A.
- Alléné C.
- Almualla M.
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- Amato A.
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- Amorosi A.
- Anand S.
- Ananyeva A.
- Andersen R.
- Anderson S. B.
- Anderson W. G.
- Andia M.
- Ando M.
- Andrade T.
- Andres N.
- Andrić T.
- Andrés-Carcasona M.
- Ansoldi S.
- Antelis J. M.
- Antier S.
- Aoumi M.
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- Ashton G.
- Aso Y.
- Assiduo M.
- Aston S. M.
- Astone P.
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- Babak S.
- Badalyan A.
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- Zweizig J.
- Álvarez-López S.
- Publication venue
- Publication date
- 07/08/2023
- Field of study
Despite the growing number of confident binary black hole coalescences
observed through gravitational waves so far, the astrophysical origin of these
binaries remains uncertain. Orbital eccentricity is one of the clearest tracers
of binary formation channels. Identifying binary eccentricity, however, remains
challenging due to the limited availability of gravitational waveforms that
include effects of eccentricity. Here, we present observational results for a
waveform-independent search sensitive to eccentric black hole coalescences,
covering the third observing run (O3) of the LIGO and Virgo detectors. We
identified no new high-significance candidates beyond those that were already
identified with searches focusing on quasi-circular binaries. We determine the
sensitivity of our search to high-mass (total mass M>70 M⊙) binaries
covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to
compare model predictions to search results. Assuming all detections are indeed
quasi-circular, for our fiducial population model, we place an upper limit for
the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level.Comment: 24 pages, 5 figure
New genetic loci link adipose and insulin biology to body fat distribution.
- Author
- Aalto Ville
- Aasarød Knut
- Abecasis Goncalo R
- Abecasis Gonçalo
- Absher Devin
- Adair Linda S
- Adam Martin
- Adeyemo Adebowale
- Ahlqvist Emma
- Ahmadi Kourosh R
- Ahola Aila
- Ainali Chrysanthi
- Akylbekova Ermeg
- Ala-Korpela Mika
- Alavere Helen
- Albagha Omar M E
- Albrecht Eva
- Alen Markku
- Alexander Myriam
- Alhenc-Gelas François
- Alizadeh Behrooz Z
- Allison Matthew A
- Alonso Nerea
- Altshuler David
- Ambite Jose Luis
- Amin Najaf
- Amouyel Philippe
- An Ping
- Anderson Carl A
- Anderson Denise
- Anderson Garnet
- Andrews Jeanette S
- Antonella Mulas
- Antti Jula
- Aragaki Aaron K
- Arking Dan E
- Arnold Alice
- Arnold Alice M
- Arora Pankaj
- Arscott Gillian M
- Artigas Maria Soler
- Arveiler Dominique
- Asiki Gershim
- Aspelund Thor
- Assimes Themistocles L
- Atalay Mustafa
- Atkinson Elizabeth J
- Aulchenko Yurii
- Avery Christy
- Bain Stephen C
- Bakker Stephan J L
- Balcells Susana
- Balkau Beverley
- Ballantyne Christie M
- Balmforth Anthony J
- Bandinelli Stefania
- Barbalic Maja
- Barrett Amy
- Barroso Ines
- Barroso Inês
- Basart Hanneke
- Basart Hanneke V
- Bataille Veronique
- Baumert Jens
- Beckmann Jacques S
- Beekman Marian
- Been Latonya F
- Beilby John
- Beilby John P
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- Scholtens Salome
- Schork Nicholas J
- Schreiber Stefan
- Schumacher Fredrick
- Schunkert Heribert
- Schwartz Stephen M
- Schwarz Peter E H
- Schäfer Arne
- Scollen Serena
- Scott James
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- Scott Robert A
- Scuteri Angelo
- Seeley Janet
- Segrè Ayellet V
- Sehmi Joban S
- Seielstad Mark
- Sekowska Magdalena
- Semple Robert
- Sengupta Sebanti
- Sennblad Bengt
- Serafinceanu Cristian
- Service Susan K
- Seshadri Sudha
- Seufferlein Thomas
- Shah Sonia
- Shah Svati H
- Sham Pak Chung
- Sharma Pankaj
- Shaw-Hawkins Sue
- Sheu Wayne H-H
- Shi Gang
- Shin So-Youn
- Shlipak Michael G
- Shohet Ralph
- Shrine Nick R G
- Shriner Daniel
- Shuldiner Alan R
- Shungin Dmitry
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- Siegbahn Agneta
- Siggeirsdottir Kristin
- Sigurdsson Gunnar
- Sijbrands Eric J G
- Silander Kaisa
- Sim Xueling
- Singleton Andrew
- Sinisalo Juha
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- Sitlani Colleen M
- Sivananthan Mohan
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- Skorpen Frank
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- Small Kerrin
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- Smit Johannes H
- Smith Albert
- Smith Erin N
- Smith George Davey
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- Snider Harold
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- Steinthorsdottir Valgerdur
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- Teumer Alexander
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- Witteman Jacqueline C M
- Wojczynski Mary K
- Wolffenbuttel Bruce H R
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- Wong Tien Y
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- Workalemahu Tsegaselassie
- Wright Alan F
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- Wu Joseph M W
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- Xiao Su-Mei
- Yajnik Chittaranjan S
- Yang Jian
- Yang Qiong
- Yang Tsun-Po
- Yao Jie
- Yengo Loïc
- Yerges-Armstrong Laura M
- Young Alicia
- Young Elizabeth H
- Young J H
- Young Lauren
- Yuan Xin
- Zaboli Ghazal
- Zalloua Pierre A
- Zarrabeitia María T
- Zelenika Diana
- Zemunik Tatijana
- Zerbini Gianpaolo
- Zgaga Lina
- Zhai Guangju
- Zhang Feng
- Zhang Qunyuan
- Zhang Weihua
- Zhao Jing Hua
- Zhao Wei
- Zheng Hou-Feng
- Zheng Wei
- Zhou Yanhua
- Zhu Haidong
- Zhu Kun
- Zhu Xiaofeng
- Zhuang Wei V
- Zhuang Wei Vivian
- Ziegler Andreas
- Zillikens M Carola
- Zimmermann Martina E
- Zitting Paavo
- Zondervan Krina T
- Zukowska-Szczechowska Ewa
- Zygmunt Marek
- Ärnlöv Johan
- Österholm Anne-May
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Evaluation of appendicitis risk prediction models in adults with suspected appendicitis
- Author
- Abbas Sh
- Abbas Sh
- Abbassi Oa
- Abbott T
- Abdelgadir Am
- Abdelrahman A
- Abdelrahman M
- Abdelrahman M
- Abdelwahed A
- Abellan M
- Abellán Am
- Abellán Am
- Abulafi M
- Acharya A
- Acosta A
- Adam Me
- Adams Re
- Adegbola So
- Adegbola So
- Adimonye A
- Adnan M
- Afshar S
- Agresta F
- Agua Ia
- Aguayo Jl
- Agudo Ar
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- Ahel J
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- Ainsworth P
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- Akhtar K
- Akinsola O
- Akram F
- Al-Faham Z
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- Amaducci E
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- Vannucchi A
- Varcada M
- Vargas-Pierola Hj
- Vaughan Em
- Vaughan Em
- Vazquez-Fernandez Ap
- Vega L
- Velchuru Vr
- Velho R
- Venkata Up
- Venkatasubramaniam Ak
- Venn Ml
- Venn Ml
- Venugopal R
- Verea S
- Veres T
- Veres T
- Verroiotou M
- Vescio G
- Vettoretto N
- Vigorita V
- Vijay V
- Vila-Zarate C
- Villarejo-Campos P
- Vinnicombe Z
- Viscosi F
- Vitish-Sharma P
- Viviani E
- Viñas Nl
- Vohra R
- Vohra R
- Vulcano I
- Waite K
- Walji Hd
- Walsh E
- Walsh Tn
- Walters Kj
- Walters U
- Wardle Bg
- Wardle Bg
- Wardle Sd
- Warren O
- Warren Oj
- Warusavitarne J
- Watfah J
- Watson N
- Wauchope J
- Weatherburn Lw
- Weaver J
- Weegenaar Cr
- Weegenaar Cr
- Welsh S
- Wensley F
- West H
- West H
- Wheatstone S
- Wheeler C
- Whewell He
- White F
- Whitehorn Se
- Whitehorn Se
- Whitehouse P
- Whiteman E
- Whittaker L
- Wiggill S
- Wijesundera K
- Wilcox G
- Wilkin R
- Wilkin R
- Wilkin R
- Wilkin R
- Wilkin R. J. W.
- Williams Gl
- Williams M
- Williams R
- Williams S
- Wilson Ej
- Wilson M
- Winter Dc
- Winter Dc
- Wolff J
- Wong A
- Wong C
- Wong J
- Wong J
- Wong Ml
- Wong Sy
- Woo R
- Wood Cs
- Woodrow C
- Woodward A
- Woodward B
- Woodward B
- Worku D
- Worku D
- Wright E
- Wright Hl
- Wu F
- Xidas A
- Yalamarthi S
- Yang P
- Yanni F
- Yardimci E
- Yasin T
- Yen Sk
- Yeung K
- Yeung K
- Yoganathan S
- Yoong S
- Youssef H
- Yow L
- Yow L
- Zaborowski A
- Zadi Az
- Zalla T
- Zarka Za
- Zarka Za
- Zarog Ma
- Zelazek M
- Zerpa C
- Zhang Ay
- Zhou S
- Zorrilla L
- Zuin M
- Zurleni Tz
- Publication venue
- 'Wiley'
- Publication date
- 01/01/2019
- Field of study
Background
Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis.
Methods
A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis).
Results
Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent).
Conclusion
Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified
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