290 results on '"Dominic Furniss"'
Search Results
52. Medical equipment library design: revealing issues and best practice using DiCoT.
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Julia Werth and Dominic Furniss
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- 2012
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53. Cognitive resilience: can we use Twitter to make strategies more tangible?
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Dominic Furniss, Jonathan Back, and Ann Blandford
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- 2012
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54. Opportunities and Barriers for Adoption of a Decision-Support Tool for Alzheimer’s Disease
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Sara Garbarino, Ann Blandford, Annemie Ribbens, Daniel C. Alexander, Dominic Furniss, Nicholas C. Firth, Neil P. Oxtoby, and Maura Bellio
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Research design ,Decision support system ,Knowledge management ,business.industry ,Computer science ,Process (engineering) ,Biomedical Engineering ,Medicine (miscellaneous) ,Health Informatics ,Computer Science Applications ,03 medical and health sciences ,Early adopter ,0302 clinical medicine ,Resource (project management) ,Health Information Management ,Work (electrical) ,Health care ,Added value ,030212 general & internal medicine ,business ,030217 neurology & neurosurgery ,Software ,Information Systems - Abstract
Clinical decision-support tools (DSTs) represent a valuable resource in healthcare. However, lack of Human Factors considerations and early design research has often limited their successful adoption. To complement previous technically focused work, we studied adoption opportunities of a future DST built on a predictive model of Alzheimer’s Disease (AD) progression. Our aim is two-fold: exploring adoption opportunities for DSTs in AD clinical care, and testing a novel combination of methods to support this process. We focused on understanding current clinical needs and practices, and the potential for such a tool to be integrated into the setting, prior to its development. Our user-centred approach was based on field observations and semi-structured interviews, analysed through workflow analysis, user profiles, and a design-reality gap model. The first two are common practice, whilst the latter provided added value in highlighting specific adoption needs. We identified the likely early adopters of the tool as being both psychiatrists and neurologists based in research-oriented clinical settings. We defined ten key requirements for the translation and adoption of DSTs for AD around IT, user, and contextual factors. Future works can use and build on these requirements to stand a greater chance to get adopted in the clinical setting.
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- 2021
55. Medial Arterial Calcification
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Fadil M. Hannan, Cynthia St. Hilaire, Ángel Millán, Yu Sato, Renu Virmani, Mirjam Schuchardt, Paolo Raggi, Roberto Ferraresi, Dominic Furniss, Peter Lanzer, Pak-Wing Fok, Jan Janzen, Rajesh V. Thakker, Julio Saez-Rodriguez, and Jan D. Lanzer
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Medial arterial calcification ,medicine.medical_specialty ,business.industry ,State of the art review ,medicine.disease ,Omics ,Internal medicine ,Diabetes mellitus ,Vascular Disorder ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Vascular calcification - Abstract
Medial arterial calcification (MAC) is a chronic systemic vascular disorder distinct from atherosclerosis that is frequently but not always associated with diabetes mellitus, chronic kidne...
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- 2021
56. Comparing Actual Practice and User Manuals: A Case Study Based on Programmable Infusion Pumps.
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Ann Blandford, Abigail Cauchi, Paul Curzon, Parisa Eslambolchilar, Dominic Furniss, Andy Gimblett, Huayi Huang, Paul Lee, Yunqiu Li, Paolo Masci 0001, Patrick Oladimeji, Atish Rajkomar, Rimvydas Ruksenas, and Harold Thimbleby
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- 2011
57. The visible and the invisible: Distributed Cognition for medical devices.
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Dominic Furniss, Ann Blandford, Atish Rajkomar, Christopher J. Vincent, and Astrid Mayer
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- 2011
58. Unremarkable errors: low-level disturbances in infusion pump use.
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Dominic Furniss, Ann Blandford, and Astrid Mayer
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- 2011
59. Confessions from a grounded theory PhD: experiences and lessons learnt.
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Dominic Furniss, Ann Blandford, and Paul Curzon
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- 2011
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60. The Development, Deployment, and Evaluation of the CLEFT-Q Computerized Adaptive Test: A Multimethods Approach Contributing to Personalized, Person-Centered Health Assessments in Plastic Surgery (Preprint)
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Conrad Harrison, Inge Apon, Kenny Ardouin, Chris Sidey-Gibbons, Anne Klassen, Stefan Cano, Karen Wong Riff, Andrea Pusic, Sarah Versnel, Maarten Koudstaal, Alexander C Allori, Carolyn Rogers-Vizena, Marc C Swan, Dominic Furniss, and Jeremy Rodrigues
- Abstract
BACKGROUND Routine use of patient-reported outcome measures (PROMs) and computerized adaptive tests (CATs) may improve care in a range of surgical conditions. However, most available CATs are neither condition-specific nor coproduced with patients and lack clinically relevant score interpretation. Recently, a PROM called the CLEFT-Q has been developed for use in the treatment of cleft lip or palate (CL/P), but the assessment burden may be limiting its uptake into clinical practice. OBJECTIVE We aimed to develop a CAT for the CLEFT-Q, which could facilitate the uptake of the CLEFT-Q PROM internationally. We aimed to conduct this work with a novel patient-centered approach and make source code available as an open-source framework for CAT development in other surgical conditions. METHODS CATs were developed with the Rasch measurement theory, using full-length CLEFT-Q responses collected during the CLEFT-Q field test (this included 2434 patients across 12 countries). These algorithms were validated in Monte Carlo simulations involving full-length CLEFT-Q responses collected from 536 patients. In these simulations, the CAT algorithms approximated full-length CLEFT-Q scores iteratively, using progressively fewer items from the full-length PROM. Agreement between full-length CLEFT-Q score and CAT score at different assessment lengths was measured using the Pearson correlation coefficient, root-mean-square error (RMSE), and 95% limits of agreement. CAT settings, including the number of items to be included in the final assessments, were determined in a multistakeholder workshop that included patients and health care professionals. A user interface was developed for the platform, and it was prospectively piloted in the United Kingdom and the Netherlands. Interviews were conducted with 6 patients and 4 clinicians to explore end-user experience. RESULTS The length of all 8 CLEFT-Q scales in the International Consortium for Health Outcomes Measurement (ICHOM) Standard Set combined was reduced from 76 to 59 items, and at this length, CAT assessments reproduced full-length CLEFT-Q scores accurately (with correlations between full-length CLEFT-Q score and CAT score exceeding 0.97, and the RMSE ranging from 2 to 5 out of 100). Workshop stakeholders considered this the optimal balance between accuracy and assessment burden. The platform was perceived to improve clinical communication and facilitate shared decision-making. CONCLUSIONS Our platform is likely to facilitate routine CLEFT-Q uptake, and this may have a positive impact on clinical care. Our free source code enables other researchers to rapidly and economically reproduce this work for other PROMs. CLINICALTRIAL
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- 2022
61. Exploring Citizen Psych-Science and the Motivations of Errordiary Volunteers.
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Charlene Jennett, Dominic Furniss, Ioanna Iacovides, Sarah Wiseman, Sandy J. J. Gould, and Anna L. Cox
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- 2014
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62. Resilience Markers for Safer Systems and Organisations.
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Jonathan Back, Dominic Furniss, Michael Hildebrandt, and Ann Blandford
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- 2008
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63. Usability Work in Professional Website Design: Insights from Practitioners' Perspectives.
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Dominic Furniss, Ann Blandford, and Paul Curzon
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- 2008
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64. Systemic inflammatory markers in neuropathic pain, nerve injury, and recovery
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David L.H. Bennett, Akira Wiberg, Georgios Baskozos, Oliver Sandy-Hindmarch, Dominic Furniss, and Annina B. Schmid
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medicine.medical_specialty ,Chemokine ,Inflammation ,Disease ,Gastroenterology ,Internal medicine ,Gene expression ,medicine ,Humans ,Carpal tunnel syndrome ,Messenger RNA ,biology ,business.industry ,Nerve injury ,medicine.disease ,Carpal Tunnel Syndrome ,Anesthesiology and Pain Medicine ,Neurology ,Neuropathic pain ,biology.protein ,Cytokines ,Neuralgia ,Neurology (clinical) ,medicine.symptom ,business - Abstract
The role that inflammation plays in human nerve injury and neuropathic pain is incompletely understood. Previous studies highlight the role of inflammation in the generation and maintenance of neuropathic pain, but the emerging evidence from the preclinical literature for its role in the resolution of neuropathic pain remains to be explored in humans. Here, we use carpal tunnel syndrome (CTS) as a human model system of nerve injury and neuropathic pain to determine changes in serum cytokine protein levels and gene expression levels before (active stage of disease) and after carpal tunnel decompression surgery (recovery). Fifty-five patients with CTS were studied, and 21 healthy age-matched and gender-matched participants served as controls. In the active stage of the disease (CTS before surgery vs healthy controls), PTGES2 mRNA was decreased in patients (adjusted P = 0.013), while transforming growth factor-β and C-C motif chemokine ligand 5 protein levels were increased (adjusted P = 0.016 and P = 0.047, respectively). In the resolution phase (CTS before surgery vs after surgery), IL-9 mRNA was increased after surgery (adjusted P = 0.014) and expression of IL-6 mRNA and IL-4 protein levels were increased before surgery (adjusted P = 0.034 and P = 0.002, respectively). IL-9 mRNA expression negatively correlated with several (neuropathic) pain scores. By contrast, protein levels of IL-4 positively correlated with pain scores. In conclusion, we demonstrate specific dysregulation of systemic cytokine expression in both the active and resolution phases of nerve injury and neuropathic pain. IL-9 represents an interesting candidate associated with resolution of nerve injury and neuropathic pain.
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- 2021
65. Usability evaluation methods in practice: understanding the context in which they are embedded.
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Dominic Furniss, Ann Blandford, and Paul Curzon
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- 2007
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66. The Role of Story Cards and the Wall in XP teams: A Distributed Cognition Perspective.
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Helen Sharp, Hugh Robinson, Judith Segal, and Dominic Furniss
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- 2006
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67. Associations of adiposity, kidney stone disease, and serum calcium concentrations; observational and genetic epidemiological studies
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Catherine E Lovegrove, Jelena Bešević, Akira Wiberg, Ben Lacey, Thomas J Littlejohns, Naomi E Allen, Michelle Goldsworthy, Jihye Kim, Fadil Hannan, Gary C Curhan, Ben Turney, Mark McCarthy, Anubha Mahajan, Rajesh V Thakker, Michael V Holmes, Dominic Furniss, and Sarah A Howles
- Abstract
BackgroundKidney stone disease (KSD) is linked to obesity, metabolic syndrome and biochemical alterations including higher serum calcium concentration. The mechanisms by which these phenotypes associate with KSD are uncertain. We aimed to establish the effects of adiposity on KSD using conventional and genetic epidemiological techniques.MethodsWe assessed observational associations between measures of adiposity and incident KSD in 479,405 people from the UK Biobank. To facilitate Mendelian randomization (MR) analyses, we undertook genome-wide association studies (GWAS) of KSD in the UK Biobank in combined and sex-specific subsets. Univariable, multivariable and mediation MR analyses were used to calculate odds ratio (OR) or beta coefficient (ß) for risk of KSD per genetically instrumented higher marker of adiposity, metabolic syndrome parameter, biochemical phenotype, and inflammation and identify violations of MR assumptions.FindingsObservational analyses demonstrated that measures of central adiposity (waist-to-hip ratio (WHR) and waist circumference (WC)) are more strongly associated with incident KSD than measures of general adiposity (body mass index (BMI)). Three novel KSD-GWAS loci were identified (SLC2A12, TRPV5, and SLC28A1); no sex-specific loci were detected. MR analyses established that higher central adiposity is causally linked to both KSD and higher adjusted serum calcium concentrations independent of BMI (one standard deviation higher WHR: OR for KSD=1·43, p=4·1×10−6; ß for serum calcium concentration=0·11mmol/L, p=2·7×10−7). Mediation analyses indicated that 12% of the effect of WHR on KSD is due its role in elevating serum calcium concentration. Our MR studies indicated that other components of the metabolic syndrome, serum uric acid levels, and biomarkers of inflammation are unlikely to be implicated in the causation of KSD.InterpretationOur study indicates that visceral adipose depots elevate serum calcium concentration and cause an increased risk of KSD. Therapies targeting central adipose deposition may affect calcium homeostasis and have utility for the prevention of KSD.
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- 2022
68. DiCoT: A Methodology for Applying Distributed Cognition to the Design of Teamworking Systems.
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Ann Blandford and Dominic Furniss
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- 2005
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69. Diagnostic accuracy of ultrasound and magnetic resonance imaging in detecting Stener lesions of the thumb: systematic review and meta-analysis
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Dominic Furniss, Zahi Qamhawi, Gareth Kiernan, Karishma Shah, James Teh, and Christine Azzopardi
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medicine.medical_specialty ,Diagnostic accuracy ,Thumb ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Collateral Ligament, Ulnar ,Ultrasonography ,medicine.diagnostic_test ,business.industry ,Quality assessment ,Ultrasound ,Hand Injuries ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,body regions ,medicine.anatomical_structure ,Meta-analysis ,Ligament ,Surgery ,Radiology ,business ,Stener lesion - Abstract
This study assesses the diagnostic accuracy of ultrasound and magnetic resonance imaging (MRI) in diagnosing Stener lesions of the thumb. MEDLINE, PubMed, Embase and Cochrane CENTRAL were searched for studies using ultrasound or MRI to detect Stener lesions following suspected thumb ulnar collateral ligament injuries. The reference standard was surgical exploration or clinical joint stability. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A random-effects bivariate meta-analysis was used to estimate pooled sensitivity and specificity. Forest plots were generated. Nine ultrasound (315 thumbs) and six MRI (107 thumbs) studies were included in meta-analysis (all high risk of bias). Pooled sensitivity and specificity for ultrasound were 95% and 94%, and for MRI were 93% and 98%. Both ultrasound and MRI demonstrate high diagnostic accuracy in detecting Stener lesions. Ultrasound is an appropriate first-line imaging modality.
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- 2021
70. Low rate of subsequent surgery and serious complications following intra-articular steroid injection for base of thumb osteoarthritis: national cohort analysis
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Matthew D Gardiner, Dominic Furniss, Daniel Prieto-Alhambra, Jane Green, Jennifer C E Lane, Richard Craig, Abigail V Shaw, Jonathan Rees, Michelle Spiteri, Benjamin F Dean, and Rachel Kuo
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Adult ,Male ,medicine.medical_specialty ,Steroid injection ,Adolescent ,Osteoarthritis ,National cohort ,Injections, Intra-Articular ,Secondary care ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Intra articular ,Rheumatology ,Thumb osteoarthritis ,medicine ,complications/adverse events ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,AcademicSubjects/MED00360 ,intra-articular injection ,Aged ,030203 arthritis & rheumatology ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Clinical Science ,Middle Aged ,medicine.disease ,thumb ,Surgery ,surgical procedures ,Clinical trial ,osteoarthritis ,Female ,Steroids ,business - Abstract
Objectives Intra-articular steroid injection is commonly used to treat base of thumb osteoarthritis (BTOA), despite a lack of large-scale data on safety and effectiveness. We estimate the incidence of serious complications and further procedures following BTOA injection, including the risk of post-operative serious surgical site infection for subsequent operative intervention. Methods Hospital Episode Statistics data linked to mortality records from 1 April 1998 to 31 March 2017 were used to identify all BTOA injections undertaken in adults in the National Health Service secondary care in England. Patients were followed up longitudinally until death or 31 March 2017. A multivariable regression with a Fine and Gray model adjusting for the competing risk of mortality in addition to age, sex and socioeconomic deprivation was used to identify factors associated with progression to further procedure. Secondary outcomes included serious complications after injection and subsequent surgical site infection. Results A total of 19 120 primary injections were performed during the 19-year period in 18 356 patients. Of these 76.5% were female; mean age 62 years (s.d. 10.6); 50.48% underwent further procedure; 22.40% underwent surgery. Median time to further intervention was 412 days (IQR 110–1945). Female sex was associated with increased risk of proceeding to surgery. Serious complication rate following injection was 0.04% (0.01–0.08) within 90 days. Of those proceeding to surgery 0.16% (0.06–0.34) presented with a wound infection within 30 days and 90 days, compared with an overall post-operative wound infection rate of 0.03% (0.02–0.05). Conclusions Very low rates of serious complications were identified following BTOA injections performed in secondary care; only one in five patients proceeded to subsequent surgery. Clinical trial registration clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03573765
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- 2021
71. Serious postoperative complications and reoperation after carpal tunnel decompression surgery in England: a nationwide cohort analysis
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Richard Craig, Jennifer C. E. Lane, Dominic Furniss, Jonathan Rees, Daniel Prieto-Alhambra, Matthew D Gardiner, and Jane Green
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musculoskeletal diseases ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Immunology ,Hazard ratio ,Population ,Postoperative complication ,Articles ,medicine.disease ,Comorbidity ,Surgery ,Rheumatology ,medicine ,Immunology and Allergy ,Complication ,business ,education ,Carpal tunnel syndrome ,Cohort study - Abstract
Background Carpal tunnel decompression surgery to treat carpal tunnel syndrome is a common procedure, yet data on safety and effectiveness of the operation in the general population remain scarce. We aimed to estimate the incidence of reoperation and serious postoperative complications (requiring admission to hospital or further surgery) following carpal tunnel decompression in routine clinical practice and to identify the patient factors associated with these adverse outcomes. Methods We did a nationwide cohort analysis including all carpal tunnel decompression surgeries in patients aged 18 years or older, done in the National Health Service in England between April 1, 1998, and March 31, 2017, using the Hospital Episode Statistics dataset linked to mortality records. Patients were followed-up until death or until the end of the study (March 31, 2017). Primary outcomes were the overall incidence of carpal tunnel decompression reoperation and serious postoperative complications (surgical site infection or dehiscence, or neurovascular or tendon injury, requiring admission to hospital or further surgery) within 30 days and 90 days after surgery. Multivariable Cox regression analysis was used to identify factors influencing complications and reoperation, and the Fine and Gray method was used to adjust for the competing risk of mortality. This study is registered with ClinicalTrials.gov, NCT03573765. Findings 855 832 carpal tunnel decompression surgeries were done between April 1, 1998, and March 31, 2017 (incidence rate 1·10 per 1000 person-years [95% CI 1·02–1·17]). 29 288 procedures (3·42%) led to carpal tunnel decompression reoperation (incidence rate 3·18 per 1000 person-years [95% CI 3·12–3·23]). Of the 855 832 initial surgeries, 620 procedures (0·070% [95% CI 0·067–0·078]) led to a serious complication within 30 days after surgery, and 698 procedures (0·082% [0·076–0·088]) within 90 days. Local complications within 90 days after surgery were associated with male sex (adjusted hazard ratio 2·32 [95% CI 1·74–3·09]) and age category 18–29 years (2·25 [1·10–4·62]). Male sex (adjusted subhazard ratio 1·09 [95% CI 1·06–1·13]), old age (>80 years vs 50–59 years: 1·09 [1·03–1·15]), and greater levels of comorbidity (Charlson score ≥5 vs 0: 1·25 [1·19–1·32]) and socioeconomic deprivation (most deprived 10% vs least deprived 10%: 1·18 [1·10–1·27]) were associated with increased reoperation risk. Interpretation To our knowledge, this is the largest national study on carpal tunnel decompression to date, providing strong evidence on serious postoperative complication and reoperation rates. Carpal tunnel decompression appears to be a safe operation in most patients, with an overall serious complication rate (requiring admission to hospital or further surgery) of less than 0·1%. Funding Versus Arthritis; Medical Research Council; Royal College of Surgeons of England and National Joint Registry research fellowship; University of Oxford; National Institute for Health Research; and National Institute for Health Research Biomedical Research Centre, Oxford.
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- 2021
72. Fieldwork for Healthcare: Guidance for Investigating Human Factors in Computing Systems
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Dominic Furniss, Rebecca Randell, Aisling Ann O'Kane, Svetlena Taneva, Helena M. Mentis, and Ann Blandford
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- 2014
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73. Fieldwork for Healthcare: Case Studies Investigating Human Factors in Computing Systems
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Dominic Furniss, Aisling Ann O'Kane, Rebecca Randell, Svetlena Taneva, Helena M. Mentis, and Ann Blandford
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- 2014
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74. A vasculature niche orchestrates stromal cell phenotype through PDGF signaling: Importance in human fibrotic disease
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Thomas B. Layton, Lynn Williams, Nan Yang, Mingjun Zhang, Carl Lee, Marc Feldmann, Glenda Trujillo, Dominic Furniss, and Jagdeep Nanchahal
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Dupuytren Contracture ,Phenotype ,Multidisciplinary ,Tumor Microenvironment ,Humans ,Stromal Cells ,Myofibroblasts ,Fibrosis - Abstract
Fibrosis is characterized by excessive matrix protein accumulation and contributes to significant morbidity and mortality in the Western world. The relative lack of effective antifibrotic therapeutics for the majority of these conditions reflects the difficulty in identifying targets for human fibrosis. Animal models fail to recapitulate all of the facets of human disease, and the limited clinical samples from patients with fibrosis of visceral organs are usually of late-stage disease [J. Nanchahal, B. Hinz, Proc. Natl. Acad. Sci. U.S.A. 113, 7291–7293 (2016)]. Here, we use Dupuytren’s disease (DD), a localized fibrotic condition of the hand, as a model to profile the vasculature niche of human fibrosis at single-cell resolution. Our spatially resolved molecular taxonomy of fibrotic blood vessels identifies distinct endothelial and pericyte populations and demonstrates a complex topological organization in the fibrotic microenvironment. In developing fibrosis, we show that the endothelium acts to promote immune regulatory fibroblast phenotype through platelet-derived growth factor (PDGF) signaling, thereby sustaining an immune cell–enriched perivascular niche. Moreover, we highlight pericytes as “housing” a putative myofibroblast precursor in DD. Overall, our results elucidate a tightly coupled vasculature niche in fibrosis that instructs the differentiation of functionally distinct stromal cells. These findings provide an important translational resource and highlight the therapeutic potential of targeting blood vessel signaling in human fibrosis.
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- 2022
75. A resilience markers framework for small teams.
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Dominic Furniss, Jonathan Back, Ann Blandford, Michael Hildebrandt, and Helena Broberg
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- 2011
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76. Human factors: the pharmaceutical supply chain as a complex sociotechnical system
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Chaofeng Guan, Brian Edwards, Charles A Gloor, Dominic Furniss, and Franck Toussaint
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human performance ,Sociotechnical system ,Process management ,Drug Industry ,Supply chain ,03 medical and health sciences ,0302 clinical medicine ,Agency (sociology) ,Health care ,Humans ,AcademicSubjects/MED00860 ,030304 developmental biology ,0303 health sciences ,Supply chain management ,business.industry ,Health Policy ,Public Health, Environmental and Occupational Health ,COVID-19 ,Human factors and ergonomics ,General Medicine ,Incentive ,Pharmaceutical Preparations ,Work (electrical) ,030220 oncology & carcinogenesis ,Perspective ,systems ,Ergonomics ,Business ,human factors - Abstract
Background The COVID-19 pandemic has exacerbated preexisting weaknesses in the global supply chain. Regional assessments by the Food and Drug Administration (FDA), European Medicines Agency (EMA), and independent consultants, have demonstrated various contributory causal factors requiring changes in policy, relationships, and incentives within the dynamic and developing networks. Human factors and ergonomics (HFE) is an approach that encourages sociotechnical systems thinking to optimize the performance of systems that involve human activity. The global supply chain can be considered such a system. However, it has neither been systematically examined from this perspective. Methods In 2015, the UK Chartered Institute of Ergonomics and Human Factors established the Pharmaceutical Sector Group. This unique group is open to all who work in the pharmaceutical sector at any level and in any discipline who share the vision of a pharmaceutical system that places an understanding of HFE at the heart of improving the use of healthcare products throughout their life cycles including their supply chains. Results For this complex system to work efficiently, it is paramount that we have effective coordination and integration between the different elements in the supply chain. HFE can give valuable insights and solutions for developing these complex social–technical systems effectively. Conclusion By partnering with international groups such as Biophorum and Bio Supply Chain Management Alliance, we wish to stimulate discussion about how sociotechnical thinking about HFE may help develop better monitoring and investigative techniques to strengthen global supply chains.
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- 2020
77. The relationship between body mass index and the risk of development of Dupuytren’s disease: a Mendelian randomization study
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Michael Ng, Michael V. Holmes, Mustafa Majeed, Akira Wiberg, and Dominic Furniss
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0303 health sciences ,medicine.medical_specialty ,business.industry ,Dupuytren disease ,030305 genetics & heredity ,Disease ,Mendelian Randomization Analysis ,Polymorphism, Single Nucleotide ,Causality ,Body Mass Index ,Dupuytren Contracture ,body regions ,03 medical and health sciences ,Waist–hip ratio ,Internal medicine ,Mendelian randomization ,Humans ,Medicine ,Surgery ,business ,Body mass index ,Genome-Wide Association Study ,030304 developmental biology - Abstract
We performed Mendelian randomization analyses of body mass index and waist–hip ratio adjusted for body mass index in Dupuytren’s disease using summary statistics from genome-wide association study meta-analyses. We found that adiposity is causally protective against Dupuytren’s disease, with the inverse-variance weighted Mendelian randomization analysis estimating that a 1 standard deviation increase in body mass index (equivalent to 4.8 kg/m2) leads to 28% (95% confidence interval: 18–37%) lower relative odds of developing Dupuytren’s disease, and a 1 standard deviation increase in waist–hip ratio adjusted for body mass index (equivalent to a waist–hip ratio of 0.09) leads to 26% (95% confidence interval: 6–42%) lower relative odds of developing Dupuytren’s disease. We conclude from this study that regardless of the well-established negative health effects of obesity, the raised body mass index is associated with a lower risk of Dupuytren’s disease and may be causally protective for the development of the disease.
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- 2020
78. Risk factors for the progression of finger interphalangeal joint osteoarthritis: a systematic review
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Stephanie R Filbay, Jennifer C E Lane, Gary S. Collins, Nigel K Arden, Karishma Shah, Xiaotian Yang, and Dominic Furniss
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medicine.medical_specialty ,Immunology ,Psychological intervention ,MEDLINE ,Hand interphalangeal joint ,Osteoarthritis ,Cochrane Library ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Quality of life ,Internal medicine ,Diabetes mellitus ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,030203 arthritis & rheumatology ,Disease progression ,business.industry ,medicine.disease ,Risk factors ,Finger joint ,Systematic Review ,business - Abstract
Progressive hand interphalangeal joint (IPJ) osteoarthritis is associated with pain, reduced function and impaired quality of life. However, the evidence surrounding risk factors for IPJ osteoarthritis progression is unclear. Identifying risk factors for IPJ osteoarthritis progression may inform preventative strategies and early interventions to improve long-term outcomes for individuals at risk of IPJ osteoarthritis progression. The objectives of the study were to describe methods used to measure the progression of IPJ osteoarthritis and identify risk factors for IPJ osteoarthritis progression. MEDLINE, EMBASE, Scopus, and The Cochrane Library were searched from inception to 19th February 2020 (PROSPERO CRD42019121034). Eligible studies assessed potential risk factor/s associated with IPJ osteoarthritis progression. Risk of bias was assessed using a modified QUIPS Tool, and a best evidence synthesis was performed. Of eight eligible studies, all measured osteoarthritis progression radiographically, and none considered symptoms. Eighteen potential risk factors were assessed. Diabetes (adjusted mean difference between 2.06 and 7.78), and larger finger epiphyseal index in males (regression coefficient β = 0.202) and females (β = 0.325) were identified as risk factors (limited evidence). Older age in men and women showed mixed results; 13 variables were not risk factors (all limited evidence). Patients with diabetes and larger finger epiphyseal index might be at higher risk of radiographic IPJ osteoarthritis progression, though evidence is limited and studies are biased. Studies assessing symptomatic IPJ osteoarthritis progression are lacking. Electronic supplementary material The online version of this article (10.1007/s00296-020-04687-1) contains supplementary material, which is available to authorized users.
- Published
- 2020
79. The Potential Role of Smart Infusion Devices in Preventing or Contributing to Medication Administration Errors: A Descriptive Study of 2 Data Sets
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Yogini Jani, Dominic Furniss, Bryony Dean Franklin, Gillian Chumbley, and Ann Blandford
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Leadership and Management ,Psychological intervention ,Original Studies ,03 medical and health sciences ,Electronic Prescribing ,0302 clinical medicine ,Electronic prescribing ,Medicine ,Humans ,030212 general & internal medicine ,Infusions, Intravenous ,Infusion Pumps ,Retrospective review ,Electronic Data Processing ,business.industry ,030503 health policy & services ,Public Health, Environmental and Occupational Health ,technology, industry, and agriculture ,Medication administration ,medicine.disease ,smart infusion pumps ,humanities ,Clinical Practice ,medication errors ,Potential harm ,Observational study ,Medical emergency ,0305 other medical science ,business ,Reporting system - Abstract
Objectives: Errors in medication administration are common, with many interventions suggested to reduce them. For intravenous infusion–related errors, “smart infusion devices” incorporating dose error reduction software are widely advocated. Our aim was to explore the role of smart infusion devices in preventing or contributing to medication administration errors using retrospective review of 2 complementary data sets that collectively included a wide range of errors with different levels of actual or potential harm. Methods: We reviewed 216 medication administration errors identified from an observational study in clinical practice and 123 medication incidents involving infusion devices reported to a national reporting system. The impact of smart infusion devices in preventing or contributing to these errors was assessed by the research team and an expert panel. Results: The data suggest that use of any infusion device rather than gravitational administration may have prevented 13% of observed errors and 8% of reported incidents; additional reductions may be possible with standalone smart infusion devices, and further potential reductions with smart infusion devices integrated with electronic prescribing and barcode administration systems. An estimated 52% to 73% of errors that occurred with traditional infusion pumps could be prevented with such integrated smart infusion devices. In the few cases where smart infusion devices were used, these contributed to errors in 2 of 58 observed errors and 7 of 8 reported incidents. Conclusions: Smart infusion devices not only prevent some medication administration errors but can also contribute to them. Further evaluation of such systems is required to make recommendations for policy and practice.
- Published
- 2020
80. Un cerveau différent
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Gwenaëlle Douaud, Akira Wiberg, and Dominic Furniss
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- 2020
81. Intravenous infusion practices across England and their impact on patient safety: a mixed-methods observational study
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A Mayer, Galal H. Galal-Edeen, Dominic Furniss, Li Wei, Bryony Dean Franklin, Ann Blandford, and Gill Chumbley
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dose error reduction software ,mixed methods ,infusion devices ,qualitative study ,MEDLINE ,ders ,patient harm ,organisational standards ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,patient safety ,medicine ,england ,030212 general & internal medicine ,resilience ,risk ,complexity science ,medication administration ,business.industry ,lcsh:Public aspects of medicine ,030503 health policy & services ,Debriefing ,Stakeholder ,lcsh:RA1-1270 ,medicine.disease ,Focus group ,practice ,medication errors ,smart pumps ,complex adaptive system ,Harm ,intravenous infusions ,observational study ,Observational study ,safety management ,Medical emergency ,hospitals ,0305 other medical science ,business ,policy ,Qualitative research - Abstract
Background Intravenous (IV) medication administration has traditionally been regarded to be error-prone with high potential for harm. A recent US multisite study revealed surprisingly few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error. Objectives To determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, and to explore sources of variation in errors, discrepancies and practices, including the contribution of smart pumps. Design Phase 1 comprised an observational point-prevalence study of IV infusions, with debrief interviews and focus groups. Observers compared each infusion against the medication order and local policy. Deviations were classified as either errors or discrepancies based on their potential for patient harm. Contextual issues and reasons for deviations were explored qualitatively during observer debriefs, and analytically in supplementary analyses. Phase 2 comprised in-depth observational studies at five of the participating sites to better understand causes of error and how safety is maintained. Workshops were held with key stakeholder groups, including health professionals and policy-makers, the public and industry. Setting Sixteen English NHS hospital trusts. Results Point-prevalence data were collected from 1326 patients and 2008 infusions. In total, 240 errors were observed in 231 infusions and 1489 discrepancies were observed in 1065 infusions. Twenty-three errors (1.1% of all infusions) were considered potentially harmful; one might have resulted in short-term patient harm had it not been intercepted, but none was judged likely to prolong hospital stay or result in long-term harm. Types and prevalence of deviations varied widely among trusts, as did local policies. Deviations from medication orders and local policies were sometimes made for efficiency or to respond to patient need. Smart pumps, as currently implemented, had little effect. Staff had developed practices to manage efficiency and safety pragmatically by working around systemic challenges. Limitations Local observers may have assessed errors differently across sites, although steps were taken to minimise differences through observer training, debriefs, and review and cleaning of data. Each in-depth study involved a single researcher, and these were limited in scale and scope. Conclusions Errors and discrepancies are common in everyday infusion administration but most have low potential for patient harm. Findings are best understood by viewing IV infusion administration as a complex adaptive system. Better understanding of performance variability to strategically manage risk may be more helpful for improving patient safety than striving to eliminate all deviations. Future work There is potential value in reviewing policy around IV infusion administration to reduce unnecessary variability, manage staff workload and engage patients, while retaining the principle that policy has to be fit for purpose, contextualised to the particular ward situation and treatment protocol, and sensitive to the risks of different medications. Further work on understanding infusion administration as a complex adaptive system might deliver new insights into managing patient safety. Funding This project was funded by the NIHR Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 7. See the NIHR Journals Library website for further project information.
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- 2020
82. How can patient-held lists of medication enhance patient safety? A mixed-methods study with a focus on user experience
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Dominic Furniss, Della Ogunleye, Hanaa Lakhdari, Marney Williams, Sara Garfield, John Norton, Bryony Dean Franklin, Fran Husson, Barry Jubraj, and Mike Etkind
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Health Personnel ,media_common.quotation_subject ,1302 Curriculum and Pedagogy ,Psychological intervention ,RECONCILIATION ,030204 cardiovascular system & hematology ,1117 Public Health and Health Services ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Nursing ,patient activation ,patient-held medication records ,Health care ,patient safety ,Humans ,Medicine ,030212 general & internal medicine ,Original Research ,media_common ,Teamwork ,Science & Technology ,business.industry ,Communication ,Health Policy ,transitions of care ,1103 Clinical Sciences ,Usability ,CARE ,Focus Groups ,Focus group ,PREVALENCE ,Health Care Sciences & Services ,Caregivers ,PRESCRIBING ERRORS ,Facilitator ,Health Policy & Services ,Thematic analysis ,business ,Life Sciences & Biomedicine - Abstract
BackgroundPatients often carry medication lists to mitigate information loss across healthcare settings. We aimed to identify mechanisms by which these lists could be used to support safety, key supporting features, and barriers and facilitators to their use.MethodsWe used a mixed-methods design comprising two focus groups with patients and carers, 16 semistructured interviews with healthcare professionals, 60 semistructured interviews with people carrying medication lists, a quantitative features analysis of tools available for patients to record their medicines and usability testing of four tools. Findings were triangulated using thematic analysis. Distributed cognition for teamwork models were used as sensitising concepts.ResultsWe identified a wide range of mechanisms through which carrying medication lists can improve medication safety. These included improving the accuracy of medicines reconciliation, allowing identification of potential drug interactions, facilitating communication about medicines, acting as an aide-mémoire to patients during appointments, allowing patients to check their medicines for errors and reminding patients to take and reorder their medicines. Different tools for recording medicines met different needs. Of 103 tools examined, none met the core needs of all users. A key barrier to use was lack of awareness by patients and carers that healthcare information systems can be fragmented, a key facilitator was encouragement from healthcare professionals.ConclusionOur findings suggest that patients and healthcare professionals perceive patient-held medication lists to have a wide variety of benefits. Interventions are needed to raise awareness of the potential role of these lists in enhancing patient safety. Such interventions should empower patients and carers to identify a method that suits them best from a range of options and avoid a ‘one size fits all’ approach.
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- 2020
83. Is venous thromboembolism prophylaxis beneficial in upper limb major joint replacement surgery? A systematic review
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Abdel Rahim Elniel, Murtaza Kadhum, and Dominic Furniss
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Shoulder ,030222 orthopedics ,medicine.medical_specialty ,Joint replacement ,business.industry ,medicine.medical_treatment ,Rehabilitation ,Elbow ,Physical Therapy, Sports Therapy and Rehabilitation ,Wrist ,Arthroplasty ,Surgery ,03 medical and health sciences ,Joint disease ,0302 clinical medicine ,medicine.anatomical_structure ,Treatment modality ,medicine ,Upper limb ,Orthopedics and Sports Medicine ,030212 general & internal medicine ,business ,Venous thromboembolism - Abstract
Background Upper limb arthroplasty is an increasingly used treatment modality for end-stage joint disease of the shoulder, elbow and wrist. Whilst complications have been reported, the risk of venous thromboembolism has received less attention when compared to the lower limb. Guidance to aid clinical decision-making remains limited. This review aims to ascertain whether venous thromboembolism prophylaxis is beneficial after upper limb major joint replacement surgery. Methods A systematic review was performed in April 2019, utilising EMBASE, MEDLINE, Cochrane and Google Scholar. All clinical studies reporting venous thromboembolism incidence and risk reduction (after prophylaxis) in upper limb joint replacement were included. Results Twenty-four observational studies were identified. The reported incidence of venous thromboembolism ranged from 0.2% to 16% (weighted mean 0.68%) and 0.2% to 0.8% (weighted mean 0.49%) in shoulder and elbow arthroplasty, respectively. No records for wrist arthroplasty were found. In the literature, baseline venous thromboembolism risk of patients without an operation is reported as 0.5%. Discussion There is a lack of good quality evidence regarding the risks and benefits of venous thromboembolism prophylaxis in upper limb major joint replacement surgery. We recommend further research, ideally formal randomised controlled trials to guide recommendations. Although venous thromboembolism is rare in upper limb surgery, surgeons should remain vigilant to this possibility.
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- 2020
84. Evaluating system utility and conceptual fit using CASSM.
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Ann Blandford, Thomas R. G. Green, Dominic Furniss, and Stephann Makri
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- 2008
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85. Exploring structure, agency and performance variability in everyday safety: An ethnographic study of practices around infusion devices using distributed cognition
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Dominic Furniss, Ann Blandford, Bryony Dean Franklin, and Astrid Mayer
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Sociotechnical system ,Process (engineering) ,media_common.quotation_subject ,Applied psychology ,Public Health, Environmental and Occupational Health ,Near miss ,Structure and agency ,Interdependence ,Agency (sociology) ,Observational study ,Thematic analysis ,Safety, Risk, Reliability and Quality ,Psychology ,Safety Research ,media_common - Abstract
Objectives Infusion safety is a recognised concern internationally. While few observational studies explore the causes of the errors that occur, even fewer describe how safety is maintained in routine practice. We sought to understand safety around infusion devices. Methods An ethnographic study of infusion device use was conducted on a haematology ward. This included observations of 51 infusions, plus their preparation where possible, during 120 h of ward observation over 11 days. Field notes were transcribed and analysed using deductive coding informed by distributed cognition. A further inductive thematic analysis highlighted new themes for making sense of the data. Results The distributed cognition analysis highlighted how infusion treatment was affected by interactions distributed across artefacts, tasks, social networks, physical space and time. These interactions occurred close to and away from the infusion: at micro, meso and macro levels according to distance from the actual process. The inductive analysis highlighted three new interdependent themes that account for how safety is constructed and compromised: structure, agency and performance variability. Discussion and conclusion Safety is constructed through the co-evolution of sociotechnical structure and agency whereby structure shapes and influences people’s behaviour and people reproduce and create structures. Everyday performance variability emerges from these interactions, including deviations in processes and outcomes (e.g. incidents, near misses and opportunities). Studies of everyday safety can explore interactions between four points of a sociotechnical structuration model: structure, agency, and satisfactory and unsatisfactory performance.
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- 2019
86. The impact of electronic prescribing systems on healthcare professionals’ working practices in the hospital setting: a systematic review and narrative synthesis
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Tiantian Ma, Bryony Dean Franklin, Soomal Mohsin-Shaikh, Maedeh Y Beykloo, Ann Blandford, Dominic Furniss, and Monsey McLeod
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PRESCRIPTION ,PERCEPTIONS ,020205 medical informatics ,1110 Nursing ,02 engineering and technology ,Health informatics ,Health administration ,0302 clinical medicine ,Healthcare professionals ,0202 electrical engineering, electronic engineering, information engineering ,IMPLEMENTATION ,Electronic prescribing and medication administration systems ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Electronic prescribing ,Narration ,Health Policy ,Nursing research ,lcsh:Public aspects of medicine ,Professional Practice ,CPOE-SYSTEM ,Working practices ,EXPERIENCES ,TIME ,SAFETY ,Health Policy & Services ,WORKFLOW ,Guideline Adherence ,Inpatient ,Life Sciences & Biomedicine ,Research Article ,PHYSICIAN ORDER ENTRY ,medicine.medical_specialty ,education ,MEDLINE ,ERRORS ,1117 Public Health and Health Services ,03 medical and health sciences ,medicine ,Humans ,Protocol (science) ,Science & Technology ,business.industry ,Clinical study design ,lcsh:RA1-1270 ,Health Care Sciences & Services ,Cross-Sectional Studies ,Family medicine ,Observational study ,business ,0807 Library and Information Studies - Abstract
Background The aim of this systematic review was to synthesise peer-reviewed literature assessing the impact of electronic prescribing (eP) systems on the working practices of healthcare professionals (HCPs) in the inpatient setting and identify implications for practice and research. Methods We searched PubMed, Medline, Embase, Cochrane and the Cumulative Index to Nursing Allied Health Literature databases for studies published from inception to November 2018. We included controlled, uncontrolled, observational and descriptive studies that explored the effect of eP on HCPs’ working practices in an inpatient setting. Data on setting, eP system and impact on working practices were extracted. Methodological quality was assessed using the Mixed Methods Appraisal Tool. Emergent themes were identified and subjected to narrative synthesis. The protocol was registered with PROSPERO (registration CRD42017075804). Results Searches identified 1301 titles and abstracts after duplicate removal. 171 papers underwent full-text review. A total of 25 studies met the inclusion criteria, from nine different countries. Nineteen were of commercial eP systems. There were a range of study designs; most (n = 14) adopted quantitative methods such as cross-sectional surveys, ten adopted qualitative approaches and a further one used mixed methods. Fourteen of the 25 studies were deemed to be of high quality. Four key themes were identified: communication, time taken to complete tasks, clinical workflow, and workarounds. Within each theme, study findings differed as to whether the effects of eP on HCPs’ working practices were positive or negative. Conclusion There is a lack of consensus within the literature on the impact of eP on HCPs’ working practices. Future research should explore the strategies resulting in a positive impact on HCPs’ working practices and learn from those that have not been successful.
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- 2019
87. Genome-wide association analysis and replication in 810,625 individuals identifies novel therapeutic targets for varicose veins
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Michael Ng, Akira Wiberg, Ahmed W-U-R., Dominic Furniss, Regent Lee, W Wang, A Auton, Krina T. Zondervan, Ashok Handa, and Team, 23andMe Research
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Angiogenesis ,business.industry ,medicine.medical_treatment ,Compression stockings ,Bioinformatics ,Biobank ,Genetic architecture ,Lymphangiogenesis ,Varicose veins ,Medicine ,Family history ,medicine.symptom ,business ,Gene - Abstract
BackgroundVaricose veins (VVs) affect one-third of Western society, with a significant subset of patients developing venous ulceration, and ongoing management of venous leg ulcers costing around $14.9 billion annually in the USA. There is no current medical management for VVs, with approaches limited to compression stockings, ablation techniques, or open surgery for more advanced disease. A significant proportion of patients report a positive family history, and heritability is ~17%, suggesting a strong genetic component. We aimed to identify novel therapeutic targets by improving our understanding of the aetiopathology and genetic architecture of VVs.MethodsWe performed the largest two-stage genome-wide association study of VVs in 401,656 subjects from UK Biobank, and replication in 408,969 subjects from 23andMe (total 135,514 varicose veins cases and 675,111 controls). We constructed a genetic risk score for VVs to investigate its use as a prognostic tool. Genes and pathways were prioritised using a suite of bioinformatic tools, and therapeutic targets identified using the Open Targets Platform.ResultsWe discovered 49 signals at 46 susceptibility loci associated with VVs, including 29 previously unreported genetic associations (28 susceptibility loci). We demonstrated that patients with VVs requiring surgery have a higher genetic risk score than those managed non-surgically. We map 237 genes to these loci, many of which are biologically relevant and tractable to therapeutic targeting or repurposing (notably VEGFA, COL27A1, EFEMP1, PPP3R1 and NFATC2). Tissue enrichment analyses implicated vascular tissue, and several genes were enriched in biological pathways relating to extracellular matrix biology, inflammation, angiogenesis, lymphangiogenesis, vascular smooth muscle cell migration, and apoptosis.ConclusionsGenes and pathways identified represent biologically plausible contributors to the pathobiology of VVs, identifying promising candidates for further investigation of venous biology and potential therapeutic targets. We have provided the proof-of-principle that genetic risk score correlates with disease severity, which represents a first step in personalised medicine approaches to varicose veins.
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- 2021
88. The association of bariatric surgery and Dupuytren's disease: a propensity score-matched cohort study
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Dominic Furniss, Anders Thorell, Jennifer C E Lane, Andrea M. Burden, Theresa Burkard, and Dag Holmberg
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Adult ,medicine.medical_specialty ,Bariatric Surgery ,body mass index ,Disease ,Cohort Studies ,Weight loss ,cohort study ,Medicine ,Humans ,Obesity ,Propensity Score ,Aged ,business.industry ,Hazard ratio ,Dupuytren's disease ,bariatric surgery ,obesity ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,Dupuytren Contracture ,Propensity score matching ,Female ,medicine.symptom ,business ,Body mass index ,Cohort study - Abstract
We aimed to assess the association between bariatric surgery and incident Dupuytren's disease (DD) using propensity score-matched cohort studies among Swedish nationwide healthcare registries. Patients aged 30-79 years who underwent bariatric surgery 2006-2019 were matched on their propensity scores, up to two obese bariatric surgery-free (unexposed) patients. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CI) for the risk of DD overall, in subgroups of age, sex, bariatric surgery type and duration of follow-up. Among 34,959 bariatric surgery patients and 54,769 propensity score-matched obese patients, the risk of DD was increased in bariatric surgery patients compared with obese unexposed patients (HR 1.30, 95% CI 1.02-1.65), among women (HR 1.36; 1.00-1.84); those undergoing gastric bypass (HR 1.33; 1.04-1.71) and those with >5 years follow-up (HR 1.63; 1.14-2.34). Our results suggest that substantial weight loss is associated with an increased risk of DD in an obese population., Journal of Hand Surgery (European Volume), 47 (3), ISSN:1753-1934, ISSN:2043-6289
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- 2021
89. Diacylglycerol kinase delta haploinsufficiency in mice causes hypocalcaemia: relevance to human Autosomal Dominant Hypoclacemia (ADH)
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Akira Wiberg, Benjamin W. Turney, Michelle Goldsworthy, Sarah A. Howles, Dominic Furniss, Rajesh Thakker, Catherine Lovegrove, Fadil Hannan, and Lee Moir
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Diacylglycerol kinase delta ,medicine.medical_specialty ,Endocrinology ,Internal medicine ,medicine ,Hypocalcaemia ,Biology ,medicine.disease ,Haploinsufficiency - Published
- 2021
90. Central adiposity and diabetes are causally associated with kidney stone disease
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Akira Wiberg, Naomi E. Allen, Sarah A. Howles, A Mahajan, Benjamin W. Turney, Catherine Lovegrove, Thomas J. Littlejohns, Mark I. McCarthy, Dominic Furniss, and Rajesh Thakker
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Kidney stone disease ,business.industry ,Diabetes mellitus ,medicine ,Central Adiposity ,Physiology ,medicine.disease ,business - Published
- 2021
91. DIRC3-IGFBP5 is a shared genetic risk locus and therapeutic target for carpal tunnel syndrome and trigger finger
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David L.H. Bennett, Sam O. Kleeman, Akira Wiberg, Georgios Baskozos, Joseph E. Powell, Benjamin Patel, Waheed-Ul-Rahman Ahmed, Michael Ng, Drew Neavin, Annina B. Schmid, and Dominic Furniss
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Oncology ,medicine.medical_specialty ,business.industry ,Genome-wide association study ,Locus (genetics) ,medicine.disease ,Phenotype ,nervous system diseases ,Internal medicine ,Expression quantitative trait loci ,Medicine ,Trigger finger ,Genetic risk ,Allele ,business ,Carpal tunnel syndrome - Abstract
Trigger finger (TF) and carpal tunnel syndrome (CTS) are two common non-traumatic hand disorders that frequently co-occur. By identifying TF and CTS cases in UK Biobank (UKB), we confirmed a highly significant phenotypic association between the diseases. To investigate the genetic basis for this association we performed a genome-wide association study (GWAS) including 2,908 TF cases and 436,579 European controls in UKB, identifying five independent loci. Colocalization with CTS summary statistics identified a co-localized locus at DIRC3 (lncRNA), which was replicated in FinnGen and fine-mapped to rs62175241. Single-cell and bulk eQTL analysis in fibroblasts from healthy donors (n=79) and tenosynovium samples from CTS patients (n=77) showed that the disease-protective rs62175241 allele was associated with increased DIRC3 and IGFBP5 expression. IGFBP5 is a secreted antagonist of IGF-1 signaling, and elevated IGF-1 levels were associated with CTS and TF in UKB, thereby implicating IGF-1 as a driver of both diseases.
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- 2021
92. A Review of Common Hand Conditions
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Akira Wiberg, David Ring, and Dominic Furniss
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Humans ,Musculoskeletal Diseases ,General Medicine ,Hand - Published
- 2022
93. Disrupting digital library development with scenario informed design.
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Ann Blandford, Suzette Keith, Richard Butterworth, Bob Fields, and Dominic Furniss
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- 2007
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94. Modern Test Theory Techniques for Adaptive Testing in Short Scales Comprising Polytomous Items: A Monte Carlo Simulation Study Comparing Rasch Measurement Theory to Unidimensional and Multidimensional Graded Response Models. (Preprint)
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Conrad J. Harrison, Bao Sheng Loe, Inge Apon, Chris J. Sidey-Gibbons, Marc C. Swan, Dominic Furniss, Anne F. Klassen, Karen W. Y. Wong Riff, Sarah L. Versnel, Maarten J. Koudstaal, Alexander C. Allori, Carolyn R. Rogers-Vizena, and Jeremy N. Rodrigues
- Abstract
BACKGROUND There are two philosophical approaches to contemporary psychometrics: Rasch measurement theory (RMT) and item response theory (IRT). Either measurement strategy can be applied to computerized adaptive testing (CAT). There are potential benefits of IRT over RMT with regards to measurement precision, but also potential risks to measurement generalizability. RMT CAT assessments have demonstrated good performance with the CLEFT-Q, a patient-reported outcome measure for use in orofacial clefting. OBJECTIVE To test whether the post-hoc application of IRT (graded response models, GRMs, and multidimensional GRMs) to RMT-validated CLEFT-Q appearance scales could improve CAT accuracy at given assessment lengths. METHODS Partial credit Rasch models, unidimensional GRMs and a multidimensional GRM were calibrated for each of the 7 CLEFT-Q appearance scales (which measure the appearance of the: face, jaw, teeth, nose, nostrils, cleft lip scar and lips) using data from the CLEFT-Q field test. A second, simulated dataset was generated with 1000 plausible response sets to each scale. Rasch and GRM scores were calculated for each simulated response set, scaled to 0-100 scores, and compared by Pearson’s correlation coefficient, root mean square error (RMSE), mean absolute error (MAE) and 95% limits of agreement. For the face, teeth and jaw scales, we repeated this in a an independent, real patient dataset. We then used the simulated data to compare the performance of a range of fixed-length CAT assessments that were generated with partial credit Rasch models, unidimensional GRMs and the multidimensional GRM. Median standard error of measurement (SEM) was recorded for each assessment. CAT scores were scaled to 0-100 and compared to linear assessment Rasch scores with RMSE, MAE and 95% limits of agreement. This was repeated in the independent, real patient dataset with the RMT and unidimensional GRM CAT assessments for the face, teeth and jaw scales to test the generalizability of our simulated data analysis. RESULTS Linear assessment scores generated by Rasch models and unidimensional GRMs showed close agreement, with RMSE ranging from 2.2 to 6.1, and MAE ranging from 1.5 to 4.9 in the simulated dataset. These findings were closely reproduced in the real patient dataset. Unidimensional GRM CAT algorithms achieved lower median SEM than Rasch counterparts, but reproduced linear assessment scores with very similar accuracy (RMSE, MAE and 95% limits of agreement). The multidimensional GRM had poorer accuracy than the unidimensional models at comparable assessment lengths. CONCLUSIONS Partial credit Rasch models and GRMs produce very similar CAT scores. GRM CAT assessments achieve a lower SEM, but this does not translate into better accuracy. Commonly used SEM heuristics for target measurement reliability should not be generalized across CAT assessments built with different psychometric models. In this study, a relatively parsimonious multidimensional GRM CAT algorithm performed more poorly than unidimensional GRM comparators.
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- 2021
95. Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis
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Stephen N. Sansom, Heba M. Ismail, Fiona E. Watt, P. Kamalathevan, Anastasios Chanalaris, Dominic Furniss, Ling Zhu, H Muhammed, Lada A. Koneva, Matthew D Gardiner, J Zarebska, Akira Wiberg, Tonia L. Vincent, and M Ng
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chemistry.chemical_classification ,business.industry ,Cartilage ,Retinoic acid ,Peroxisome proliferator-activated receptor ,Osteoarthritis ,medicine.disease ,In vitro ,ALDH1A2 ,chemistry.chemical_compound ,Talarozole ,medicine.anatomical_structure ,chemistry ,In vivo ,Cancer research ,Medicine ,business - Abstract
Over 40% of individuals will develop osteoarthritis (OA) during their lifetime, yet there are currently no licensed disease modifying treatments for this disabling condition. Common polymorphic variants in ALDH1A2, that encodes the key enzyme in the synthesis of all-trans retinoic acid (atRA), have been associated with severe hand OA. In this study, we sought to elucidate the biological significance of this association. We first confirmed that ALDH1A2 risk variants were associated with hand OA in UK Biobank. Articular cartilage was acquired from 33 consenting individuals with hand OA at the time of routine hand OA surgery. They were stratified by genotype and RNA sequencing performed. A reciprocal relationship between ALDH1A2 mRNA and inflammatory genes was observed. Articular cartilage injury up-regulates similar inflammatory genes by a process that we have previously termed mechanoflammation, and which we believe is a primary driver of OA. Cartilage injury was also associated with a concomitant drop in atRA-dependent genes, indicative of cellular atRA levels, and both responses to injury were reversed using talarozole, a retinoic acid metabolism blocking agent (RAMBA). Suppression of mechanoflammation by talarozole was mediated by a peroxisome proliferator activated receptor (PPAR)-γ dependent mechanism. Talarozole, delivered by minipump, was able to suppress mechano-inflammatory genes in articular cartilage in vivo 6h after mouse knee joint destabilization, and reduced cartilage degradation and osteophyte formation after 4 weeks. These data show that boosting atRA suppresses mechanoflammation in the articular cartilage in vitro and in vivo, and identifies RAMBAs as potential disease modifying drugs in OA.One Sentence SummaryAnalysis of hand OA cartilage stratified by ALDH1A2 polymorphic variants reveals a targetable, anti-inflammatory role for retinoic acid in OA.
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- 2021
96. 1540 Genome-Wide Association Analysis In 401,583 Individuals Identifies Novel Therapeutic Targets for Haemorrhoids
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Dominic Furniss, Waheed-Ul-Rahman Ahmed, Krina T. Zondervan, M Ng, N J Smart, and Akira Wiberg
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business.industry ,Genome-Wide Association Analysis ,Medicine ,Surgery ,Computational biology ,business - Abstract
Aim To elucidate the genetic architecture of haemorrhoids and identify genes and biological pathways central to their pathobiology. Method We report the first ever genome-wide association study of haemorrhoids in 31,652 cases and 369,931 controls from UK Biobank. Genes and biological pathways were prioritised using several bioinformatic approaches, and potential therapeutic targets were identified in the Open Targets Platform. A weighted genetic risk score (wGRS) for haemorrhoids was constructed to compare genetic susceptibility in surgical vs non-surgical haemorrhoids patients. Results Twelve novel genome-wide significant susceptibility loci were discovered to be associated with haemorrhoids. Seventeen genes were mapped to these loci, and gene sets in biological pathways relating to extracellular matrix regulation and TGF-β signalling were strongly implicated. Seven gene-products (41.2%) were predicted tractable to antibody and/or small molecule targeting, and three products (17.6%) have known pharmaceutical interactions (ACHE, ADRA2B, ELN). The wGRS analysis demonstrated that haemorrhoid patients requiring surgery have a higher inherent genetic susceptibility than those managed non-surgically (P = 4.58 × 10-27). Conclusions This study has advanced our understanding of haemorrhoids pathobiology with the identification of several biologically plausible genes and pathways, many of which demonstrate strong therapeutic potential. The wGRS correlated with disease severity, representing a first step in personalised medicine approaches to haemorrhoids.
- Published
- 2021
97. 1625 Genome-Wide Association Analysis and Replication In 810,625 Individuals Identifies Novel Therapeutic Targets for Varicose Veins
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Ahmed W-U-R., W Wang, Akira Wiberg, A Handa, Krina T. Zondervan, M Ng, A Auton, Dominic Furniss, and Regent Lee
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business.industry ,Varicose veins ,Replication (statistics) ,medicine ,Genome-Wide Association Analysis ,Surgery ,Computational biology ,medicine.symptom ,business - Abstract
Aim To elucidate the genetic architecture of varicose veins (VVs) and identify genes and biological pathways central to their pathobiology. Method We performed hitherto the largest two-stage genome-wide association study of VVs in 401,656 subjects from UK Biobank, and replication in 408,969 subjects from 23andMe, Inc (total 135,514 VVs cases and 675,111 controls). Genes and biological pathways were prioritised using several bioinformatic approaches, and potential therapeutic targets were identified in the Open Targets Platform. A weighted genetic risk score (wGRS) for VVs was constructed to compare genetic susceptibility in surgical vs non-surgical VVs patients. Results 109 genome-wide significant (P ≤ 5 × 10-8) loci were identified in UK Biobank, 46 of which successfully replicated in the 23andMe cohort. Twenty-eight loci have not been previously reported. We mapped 237 genes to these loci, many of which are biologically relevant and tractable to therapeutic targeting or repurposing (notably VEGFA, COL27A1, EFEMP1, PPP3R1 and NFATC2). Tissue enrichment analyses implicated vascular tissue, and several genes were enriched in biological pathways relating to extracellular matrix biology, inflammation, angiogenesis, lymphangiogenesis, vascular smooth muscle cell migration, and apoptosis. The wGRS analysis demonstrated that VVs patients requiring surgery have a higher inherent genetic susceptibility than those managed non-surgically (P = 2.46 × 10−13). Conclusions This study has advanced our understanding of VVs pathobiology with the identification of several biologically plausible genes and pathways, many of which demonstrate strong therapeutic potential. The wGRS correlated with disease severity, representing a first step in personalised medicine approaches to VVs.
- Published
- 2021
98. Temporal Trends and Geographical Variation in Dupuytren Disease Surgery in England: A Population-Based Cohort Study
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Simon G F Abram, Jennifer C E Lane, Dominic Furniss, Richard Craig, Daniel Prieto-Alhambra, Osaid Alser, Jonathan Rees, Albert Prats-Uribe, and Abigail V Shaw
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education.field_of_study ,medicine.medical_specialty ,Percutaneous ,business.industry ,Dupuytren disease ,Population ,MEDLINE ,Disease ,State Medicine ,Surgery ,Fasciotomy ,Cohort Studies ,Dupuytren Contracture ,England ,Health care ,medicine ,Humans ,Residence ,education ,business ,Cohort study - Abstract
Background Dupuytren disease (DD) is a common fibroproliferative disease of the palmar fascia. The mainstay of DD treatment in England is surgery with either percutaneous needle fasciotomy, limited fasciectomy, or dermofasciectomy. This study aimed to investigate the temporal trends and geographical variation of primary DD surgery in England. Methods A longitudinal population-based cohort study was perfomed using the Hospital Episode Statistics database from April 1, 2007, to March 31, 2017. Directly standarized rates were estimated over time (between financial years 2007-2008 and 2016-2017) and by geographic region (by clinical commissioning groups [CCGs]; financial years 2010-2011, 2013-2014, and 2016-2017). The Office for National Statistics midyear population estimates were used as the reference population. Main findings Primary DD surgery was undertaken at a steadily increasing rate from financial year 2007 to 2008, to 2016 to 2017 in England. There was a striking 3.6-fold variation in the rates of primary DD surgery among National Health Service CCGs in England place of residence. Conclusions This significant variation in DD surgical treatment in England suggests a need for the development of standardized surgical practice across all CCGs and National Health Service hospitals, promoting equality of access to cost-effective health care.
- Published
- 2021
99. O16 Development of risk calculators for hand osteoarthritis and invasive treatment
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Alan J. Silman, Dominic Furniss, Nigel K Arden, Karishma Shah, and Gary S. Collins
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medicine.medical_specialty ,Life style ,business.industry ,Secondary data ,Osteoarthritis ,Thumb ,medicine.disease ,medicine.anatomical_structure ,Thumb osteoarthritis ,medicine ,Physical therapy ,Surgery ,business ,Diagnostic radiologic examination ,Hand osteoarthritis - Abstract
Aim Develop a prediction model for incident radiographic IPJ osteoarthritis when multiple clinical risk factors are present. Methods This study used secondary analysis from the Chingford 1000 Women Study, a prospective cohort of women aged 45 to 64 years. At baseline, anthropometric, clinical, and lifestyle measured had been collected. Hand radiographs had been taken at baseline and 10 years, read using the Kellgren-Lawrence atlas. For the current study, participants with osteoarthritis (Kellgren-Lawrence ≥2) in any IPJ at baseline were excluded. Risk factors were selected from baseline based on biological plausibility, a published systematic review, and a Delphi study of Hand Surgeons. Incident osteoarthritis was diagnosed at 10 years if ≥ 1 IPJ was Kellgren-Lawrence ≥2. The model was built with logistic regression and elastic net penalisation, and performance assessed through discrimination (c-statistic) and calibration (c-slope). Complete case analysis was used. Results Of 1,003 participants, 459 participants were included in this study (median age: 51 years, 202 (44%) with IPJ osteoarthritis at follow-up). Manual occupation (P Conclusions Osteoarthritis at the base of thumb and IPJs might be a continuum of the same disease. Knowledge of these modifiable and non-modifiable risk factors can inform prevention strategies.
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- 2021
100. Hand Osteoarthritis: investigating Pain Effects of estrogen-containing therapy (HOPE-e): a protocol for a feasibility randomised placebo-controlled trial
- Author
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Mae Chester-Jones, Matthew D Gardiner, Sue Woollacott, Charles Mackworth-Young, Katy Vincent, Dominic Furniss, Marion Watson, Victoria Glover, Malvika Gulati, Susan J Dutton, Anne Francis, Sarah E Lamb, Joanna Black, Fiona E. Watt, Ioana R Marian, Megan Goff, Jennifer A E Williams, Tonia L. Vincent, and Vicki S Barber
- Subjects
Medicine (General) ,MENOPAUSE ,medicine.medical_specialty ,HORMONE-THERAPY ,medicine.medical_treatment ,Population ,Placebo-controlled study ,Medicine (miscellaneous) ,Research & Experimental Medicine ,KNEE OSTEOARTHRITIS ,Placebo ,law.invention ,Study Protocol ,03 medical and health sciences ,R5-920 ,0302 clinical medicine ,Quality of life ,Randomized controlled trial ,QUALITY-OF-LIFE ,law ,Hand osteoarthritis ,medicine ,030212 general & internal medicine ,education ,education.field_of_study ,Science & Technology ,HIP ,030219 obstetrics & reproductive medicine ,JOINT ,business.industry ,Feasibility ,Hormone replacement therapy (menopause) ,SYMPTOMATIC HAND ,medicine.disease ,Estrogen ,Clinical trial ,REPLACEMENT ,Menopause ,Medicine, Research & Experimental ,Hormone replacement therapy ,POSTMENOPAUSAL WOMEN ,RELIABILITY ,Physical therapy ,business ,Life Sciences & Biomedicine - Abstract
Background Hand osteoarthritis (OA) is a common condition, causing pain, stiffness and reduced quality of life. Incidence is higher amongst women, particularly around the age of the menopause. Whilst the relationship between sex hormones and OA has been studied in vitro, in epidemiological studies and in clinical trials of hormone replacement therapy (HRT), this study is the first to investigate the effect of estrogen-containing therapy on hand pain in post-menopausal women with symptomatic hand OA in a randomised study design. Methods This is a feasibility study of a double-blinded placebo-controlled intervention with 1:1 randomisation to either a combination of conjugated estrogens 0.45 mg and bazedoxifene acetate 20 mg (Duavive) or placebo. The target population is post-menopausal women with symptomatic hand OA, aiming to recruit 60–90 study participants. The primary objective is to assess the feasibility of a future fully powered randomised controlled trial (RCT). Participants will take the study medication for 24 weeks and be followed up for 28 weeks after randomisation. The primary outcomes used to determine feasibility are eligible participant identification rates and routes; recruitment, randomisation and retention rates of eligible participants; study medication compliance; and the likelihood of unintentional unblinding. Secondary outcomes include measures of hand pain, function, appearance and menopausal symptoms. An end of study questionnaire and focus groups will help to refine the final protocol for a full study. Discussion Identifying new treatments for symptomatic hand OA is a recognised research priority. The study will help us to understand whether there are sufficient interested and eligible individuals in this target population who would consider HRT for their hand symptoms. It will provide proof-of-concept RCT data on the effects of HRT on hand pain and other clinically relevant outcomes in this population. The study will gain valuable information on the feasibility of a full RCT and how best to run this. The findings will be published in a peer-reviewed journal and presented at a relevant conference. Trial registration ISRCTN12196200 registered on 15 January 2019.
- Published
- 2021
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