Search

As of the end of March 2020, the covid-19 pandemic has resulted in over 850 000 confirmed cases and an estimated 42 000 deaths worldwide.1 All agree that safe and effective therapies for treatment and prevention are urgently needed. In the midst of this rapidly progressing crisis, evidence has emerged suggesting that antimalarial medications, such as hydroxychloroquine (HCQ), may be efficacious for covid-19 treatment. After amplification from politicians, news outlets and social media, a rush to acquire supplies of HCQ resulted in worldwide shortages. Recent government policies may have exacerbated these issues, where wider use in both covid-19 treatment and prevention were authorised or recommended by India, the US Food and Drug Administration and other countries.2–4 In response to dwindling supplies, several US states have issued restrictions on HCQ use including limiting dispensation quantities and verifying indications.5–8 Rheumatologists, researchers and patient partners must advocate for the appropriate distribution and use of HCQ, as millions of people with rheumatic diseases worldwide depend on HCQ to control disease activity and maintain quality of life. In doing so, we must also remind ourselves to ‘make haste slowly’ ( festina lente ). Emanuel et al 9 published a well-timed commentary suggesting the following principles for fairly allocating scarce resources during the covid-19 crisis: equal treatment, attempts to maximise benefits and prioritising the most vulnerable. These recommendations echo prior guidance published in 2016 by the WHO on how to address future infectious disease outbreaks.10 The report cautioned that ‘special attention should be given to ensuring that persons who face heightened susceptibility to harm or injustice during infectious disease outbreaks are able to contribute to decisions about infectious disease outbreak planning and response’. This ethical framework offers health systems a structure for approaching the use and distribution of HCQ during the covid-19 pandemic to minimise …

We thank Gyorfi et al for their correspondence.1 The case they present demonstrates a potentially important point that was reported in our manuscript2: the effect of systemic glucocorticoids may worsen outcomes in patients with rheumatic disease. However, as has been highlighted recently by the results of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial, systemic glucocorticoids may have a role to play in treating COVID-19.3 Noteworthy, in the RECOVERY trial, dexamethasone (6 mg daily for 10 days) only reduced deaths in the patients that were ventilated (one-third reduction) or receiving oxygen (one-fifth reduction) but no benefit was seen among those patients who did not require respiratory support; moreover, the trial did not study …

Diagnosing bacterial infection in the unwell or febrile child is a common challenge faced by all paediatricians. Despite the advent of novel molecular techniques, there is ongoing need for diagnostic assays with adequate performance and turnaround time to facilitate safe clinical decision-making when bacterial sepsis is suspected, such as whether to commence empirical treatment with antibiotics. Procalcitonin is an established marker of infection that has a potential role in the diagnosis and exclusion of serious or invasive bacterial infection in neonates and children. Although enthusiastically adopted in many countries and institutions, national guidance in the UK does not yet support its routine use. This article reviews the relevant literature on the use of procalcitonin measurement in common paediatric clinical scenarios.

Background:There is limited data regarding the risk of hospitalisation in patients with rheumatic disease and COVID-19 in Ireland.Objectives:We used the COVID-19 Global Rheumatology Alliance (GRA) registry data to study outcomes and their predictors.Methods:We examined data on patients and their disease-related characteristics entered into the COVID-19 GRA provider registry from Ireland (24th March 2020 to 31st August 2020). Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with hospitalisation.Results:Of 105 patients, 47 (45.6%) were hospitalised and 10 (9.5%) died. Multivariable logistic regression analysis showed age (OR=1.06, 95%CI 1.01 to 1.10), number of comorbidities (OR=1.93, 95%CI 1.11 to 3.35), and glucocorticoid use (OR=15.01, 95%CI 1.77 to 127.16) were significantly associated with hospitalisation. A diagnosis of inflammatory arthritis was associated with a lower odds of hospitalisation (OR=0.09, 95%CI 0.02 to 0.32).All significant variable modelMost parsimonious modelUnadjusted OR (95% CI)Adjusted OR (95%CI)*Adjusted p-value*Adjusted OR (95%CI)&Adjusted p-value&Female0.45 (0.20-1.02)0.33 (0.05-2.23)0.34 (0.09-1.36)0.128Age (years)1.08 (1.05-1.11)1.04 (0.97-1.10)0.2241.06 (1.01-1.10)0.010Inflammatory arthritis0.11 (0.05-0.28)0.14 (0.02-0.95)0.0440.09 (0.02-0.32)Connective Tissue Disease and Other1.56 (0.62 - 3.92)No comorbidities0.11 (0.04-0.30)0.76 (0.09-6.58)0.802Most common comorbiditiesCOPD / asthma4.77 (1.23-18.54)3.09 (0.16-60.07)0.456CVD3.40 (1.31-8.85)0.11 (0.01-1.88)0.129Hypertension3.71 (1.52-9.08)0.56 (0.04-7.94)0.668Obesity0.58 (0.10-3.30)Number of comorbidities (Median, IQR)3.01 (1.92-4.72)2.99 (0.59-15.02)0.1841.93 (1.11-3.35)0.020Never Smokerref.0.889Ever Smoker3.17 (1.18-8.89)1.19 (0.10-13.68)Medication prior to COVID-19 diagnosisGlucocorticoids9.26 (1.95-43.89)18.14 (1.13-290.81)0.04115.01 (1.77-127.16)0.013csDMARD monotherapy0.42 (0.17-1.00)b/tsDMARD (monotherapy or in combination with csDMARD)0.24 (0.10-0.58)1.36 (0.19-9.72)0.557Conclusion:Increasing age, comorbidity burden, and glucocorticoid use were associated with hospitalisation, while a diagnosis of inflammatory arthritis was associated with lower odds of hospitalization.Disclosure of Interests:Richard Conway Speakers bureau: Janssen, Roche, Sanofi, Abbvie, Elena Nikiphorou Speakers bureau: AbbVie, Eli-Lilly, Gilead, Celltrion, Pfizer, Sanofi, Christiana Demetriou: None declared, Candice Low: None declared, Kelly Leamy: None declared, John Ryan: None declared, Ronan Kavanagh: None declared, Alexander Fraser: None declared, John Carey: None declared, Paul O’Connell: None declared, Rachael Flood: None declared, Ronan Mullan: None declared, David Kane: None declared, Philip Robinson Speakers bureau: UCB, Roche, Pfizer, Gilead, Janssen, Novartis, Eli Lilly, Abbvie, Grant/research support from: Abbvie, UCB, Novartis, Janssen, Pfizer, Jean Liew Grant/research support from: Pfizer, Rebecca Grainger Speakers bureau: Pfizer, Cornerstones, Janssen, Novartis, Abbvie, Geraldine McCarthy: None declared.

We appreciate the interest in our paper1 and the opportunity to provide additional clarification and context. It is now generally accepted that there are different phases of COVID-19 illness.2 Our study investigated baseline use, presumably at the earliest phase of infection where viral replication is most pronounced. Clinical trials have typically tested the efficacy of medication use among hospitalised patients where pathologic hyperinflammation may mediate poor clinical outcomes. Therefore, the timing of immunomodulator use related to the COVID-19 disease course may have different effects on clinical outcomes, and trial results may not be able to be extrapolated to observational studies of baseline medication use. Observational results may lend insight into key immune mechanisms that could alter the trajectory of COVID-19, but the results could be confounded. To limit possible confounding by indication, our study used an active comparator study design that included patients with a single disease, rheumatoid arthritis (RA), who were taking biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD).1 In doing so, we included patients with similar disease severity who had the opportunity to receive advanced therapy. We compared each class of b/tsDMARD to tumour necrosis factor inhibitors (TNFi) since this was the most commonly used b/tsDMARD. Of note, medications were collected by mechanism of action, rather than individual drugs. While this observational study design minimised possible confounding, all patients were on some immunomodulator regimen, so it is possible that some of these medications might have had favourable effects on the COVID-19 disease trajectory. We agree that our finding associating rituximab for use in RA with worsened COVID-19 severity compared with TNFi use1 has biologic plausibility due to the importance of the adaptive immune response to infections and to SARS-CoV-2 in particular. A previous GRA study also associated rituximab use with increased COVID-19-related …

Background:Evidence suggests that gout is associated with high health care costs and that many inpatient admissions are preventable (1). Understanding the driver of health care costs will allow more targeted intervention.Objectives:To examine factors associated with high health service utilisation and cost in patients admitted to hospital with gout, using whole-population linked hospital, WA cancer registration, Emergency Department (ED) and death data (2).Methods:The study included patients (18 to 84 years) who had been admitted to hospital with a primary or co-diagnosis of gout for the first time between 1 Jan 02 and 31 Dec 09 Hospital costs were calculated per patient using DRG codes and ED costs were calculated from URG codes. Costs are presented in Australian dollars. Follow-up was completed at five years post their initial gout hospitalisation, at death, or at the 31th of December 2014. Both univariable and multivariable analysis was conducted for each patient characteristic. Independent variables were assessed for collinearity. Collinearity was assumed present where the correlation co-efficient was greater than 0.7.Results:4,379 individuals were included. In the following five years, there was 22,222 ED attendances (median cost, $1826 per patient (IQR: $433 - $4,414)), and 58,920 hospital admissions, (median cost, $25,009 per patient (IQR: $6,844 - $60,535)). 4,059 (18.3%) ED attendances and 3,834 (6.5%) hospital admissions were potentially preventable. Gout was not a major driver of events, with 341 (1.5%) ED attendances and 620 (1.1%) hospital admissions coded with a primary diagnosis of gout. In the univariable analysis (Table 1), Aboriginality and smoking were associated with an increased number of both ED attendances and hospital admissions. Increased socio-economic status was associated with a reduction in ED attendances, however, this was not reflected in hospital admissions.Conclusion:Patients admitted to hospital with gout are highly likely to be re-admitted or attend ED in the following 5 years. Many of these contacts are preventable, but are usually driven by comorbidities rather than gout.References:[1]Loh K, . Intern Med J. 2020 Mar;50(3):386.[2]https://www.datalinkage-wa.org.au.Acknowledgements:The authors wish to thank the staff at the Western Australian Data Linkage Branch and the Hospital Morbidity Data Collection, and the Death Registrations and the Emergency Department Data Collection.Disclosure of Interests:None declared.

Background:An increased risk of severe COVID-19 outcomes may be seen in patients with autoimmune diseases on moderate to high daily doses of glucocorticoids, as well as in those with comorbidities. However, specific information about COVID-19 outcomes in SLE is scarce.Objectives:To determine the characteristics associated with severe COVID-19 outcomes in a multi-national cross-sectional registry of COVID-19 patients with SLE.Methods:SLE adult patients from a physician-reported registry of the COVID-19 GRA were studied. Variables collected at COVID-19 diagnosis included age, sex, race/ethnicity, region, comorbidities, disease activity, time period of COVID-19 diagnosis, glucocorticoid (GC) dose, and immunomodulatory therapy. Immunomodulatory therapy was categorized as: antimalarials only, no SLE therapy, traditional immunosuppressive (IS) drug monotherapy, biologics/targeted synthetic IS drug monotherapy, and biologic and traditional IS drug combination therapy. We used an ordinal COVID-19 severity outcome defined as: not hospitalized/hospitalized without supplementary oxygen; hospitalized with non-invasive ventilation; hospitalized with mechanical ventilation/extracorporeal membrane oxygenation; and death. An ordinal logistic regression model was constructed to assess the association between demographic characteristics, comorbidities, medications, disease activity and COVID-19 severity. This assumed that the relationship between each pair of outcome groups is of the same direction and magnitude.Results:Of 1069 SLE patients included, 1047 (89.6%) were female, with a mean age of 44.5 (SD: 14.1) years. Patient outcomes included 815 (78.8%) not hospitalized/hospitalized without supplementary oxygen; 116 (11.2) hospitalized with non-invasive ventilation, 25 (2.4%) hospitalized with mechanical ventilation/extracorporeal membrane oxygenation and 78 (7.5%) died. In a multivariate model (n=804), increased age [OR=1.03 (1.01, 1.04)], male sex [OR =1.93 (1.21, 3.08)], COVID-19 diagnosis between June 2020 and January 2021 (OR =1.87 (1.17, 3.00)), no IS drug use [OR =2.29 (1.34, 3.91)], chronic renal disease [OR =2.34 (1.48, 3.70)], cardiovascular disease [OR =1.93 (1.34, 3.91)] and moderate/high disease activity [OR =2.24 (1.46, 3.43)] were associated with more severe COVID-19 outcomes. Compared with no use of GC, patients using GC had a higher odds of poor outcome: 0-5 mg/d, OR =1.98 (1.33, 2.96); 5-10 mg/d, OR =2.88 (1.27, 6.56); >10 mg/d, OR =2.01 (1.26, 3.21) (Table 1).Table 1.Characteristics associated with more severe COVID-19 outcomes in SLE. (N=804)OR (95% CI)Age, years1.03 (1.01, 1.04)Sex, Male1.93 (1.21, 3.08)Race/Ethnicity, Non-White vs White1.47 (0.87, 2.50)RegionEuropeRef.North America0.67 (0.29, 1.54)South America0.67 (0.29, 1.54)Other1.93 (0.85, 4.39)Season, June 16th 2020-January 8th 2021 vs January-June 15th 20201.87 (1.17, 3.00)Glucocorticoids0 mg/dayRef.0-5 mg/day1.98 (1.33, 2.96)5-10 mg/day2.88 (1.27, 6.56)=>10 mg/day2.01 (1.26, 3.21)Medication CategoryAntimalarial onlyRef.No IS drugs2.29 (1.34, 3.91)Traditional IS drugs as monotherapy1.17 (0.77, 1.77)b/ts IS drugs as monotherapy1.00 (0.37, 2.71)Combination of traditional and b/ts IS1.00 (0.55, 1.82)Comorbidity BurdenNumber of Comorbidities (excluding renal and cardiovascular disease)1.39 (0.97, 1.99)Chronic renal disease2.34 (1.48, 3.70)Cardiovascular disease1.93 (1.34, 3.91)Disease Activity, Moderate/ high vs Remission/ low 2.24 (1.46, 3.43)IS: immunosuppressive. b/ts: biologics/targeted syntheticsConclusion:Increased age, male sex, glucocorticoid use, chronic renal disease, cardiovascular disease and moderate/high disease activity at time of COVID-19 diagnosis were associated with more severe COVID-19 outcomes in SLE. Potential limitations include possible selection bias (physician reporting), the cross-sectional nature of the data, and the assumptions underlying the outcomes modelling.Acknowledgements:The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, EULAR) the UK National Health Service, the National Institute for Health Research (NIHR), or the UK Department of Health, or any other organization.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Pfizer, Janssen, Graciela S Alarcon: None declared, Andrea Seet: None declared, Zara Izadi: None declared, Cristina Reategui Sokolova: None declared, Ann E Clarke Consultant of: AstraZeneca, BristolMyersSquibb, GlaxoSmithKline, Exagen Diagnostics, Leanna Wise: None declared, Guillermo Pons-Estel: None declared, Maria Jose Santos: None declared, Sasha Bernatsky: None declared, Lauren Mathias: None declared, Nathan Lim: None declared, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum unrelated to this work., Grant/research support from: Amgen and Bristol-Myers Squibb, Zachary Wallace Consultant of: Viela Bio and MedPace, Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: MS, UCB, and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, Pfizer, Grant/research support from: AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB, Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB, Grant/research support from: Lilly, Mylan, Pfizer, Loreto Carmona: None declared, Elsa Mateus Grant/research support from: Pfizer, Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA, Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Patti Katz: None declared, Lindsay Jacobsohn: None declared, Samar Al Emadi: None declared, Emily Gilbert: None declared, Ali Duarte-Garcia: None declared, Maria Valenzuela-Almada: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Philippe Dieudé Consultant of: Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche, Janssen unrelated to this work, Grant/research support from: Bristol-Myers Squibb, Chugaii, Pfizer, unrelated to this work, Elena Nikiphorou: None declared, Vanessa Kronzer: None declared, Namrata Singh: None declared, Beth Wallace: None declared, Akpabio Akpabio: None declared, Ranjeny Thomas: None declared, Suleman Bhana Consultant of: AbbVie, Horizon, Novartis, and Pfizer (all

Background:Acute Respiratory Distress Syndrome (ARDS) is a life-threatening complication of COVID-19 and has been reported in approximately one-third of hospitalized patients with COVID-191. Risk factors associated with the development of ARDS include older age and diabetes2. However, little is known about factors associated with ARDS in the setting of COVID-19, in patients with rheumatic disease or those receiving immunosuppressive medications. Prediction algorithms using traditional regression methods perform poorly with rare outcomes, often yielding high specificity but very low sensitivity. Machine learning algorithms optimized for rare events are an alternative approach with potentially improved sensitivity for rare events, such as ARDS in COVID-19 among patients with rheumatic disease.Objectives:We aimed to develop a prediction model for ARDS in people with COVID-19 and pre-existing rheumatic disease using a series of machine learning algorithms and to identify risk factors associated with ARDS in this population.Methods:We used data from the COVID-19 Global Rheumatology Alliance (GRA) Registry from March 24 to Nov 1, 2020. ARDS diagnosis was indicated by the reporting clinician. Five machine learning algorithms optimized for rare events predicted ARDS using 42 variables covering patient demographics, rheumatic disease diagnoses, medications used at the time of COVID-19 diagnosis, and comorbidities. Model performance was assessed using accuracy, area under curve, sensitivity, specificity, positive predictive value, and negative predictive value. Adjusted odds ratios corresponding to the 10 most influential predictors from the best performing model were derived using hierarchical multivariate mixed-effects logistic regression that accounted for within-country correlations.Results:A total of 5,931 COVID-19 cases from 67 countries were included in the analysis. Mean (SD) age was 54.9 (16.0) years, 4,152 (70.0%) were female, and 2,399 (40.5%) were hospitalized. ARDS was reported in 388 (6.5% of total and 15.6% of hospitalized) cases. Statistically significant differences in the risk of ARDS were observed by demographics, diagnoses, medications, and comorbidities using unadjusted univariate comparisons (data not shown). Gradient boosting machine (GBM) had the highest sensitivity (0.81) and was considered the best performing model (Table 1). Hypertension, interstitial lung disease, kidney disease, diabetes, older age, glucocorticoids, and anti-CD20 monoclonal antibodies were associated with the development of ARDS while tumor necrosis factor inhibitors were associated with a protective effect (Figure 1).Table 1.Performance of machine learning algorithms.GBMSVMGLMNETNNETRFAccuracy0.790.680.660.660.67AUC0.750.700.740.580.74Sensitivity0.810.680.650.680.67Specificity0.490.600.730.480.68PPV0.960.960.970.950.97NPV0.160.120.130.090.13GBM: Gradient Boosting Machine, SVM: Support vector machines, GLMNET: Lasso and Elastic-Net Regularized Generalized Linear Models, NNET: Neural Networks, RF: Random Forest. AUC: Area Under Curve; PPV: Positive Predictive Value; NPV: Negative Predictive Value.Conclusion:In this global cohort of patients with rheumatic disease, a machine learning model, GBM, predicted the onset of ARDS with 81% sensitivity using baseline information obtained at the time of COVID-19 diagnosis. These results identify patients who may be at higher risk of severe COVID-19 outcomes. Further studies are necessary to validate the proposed prediction model in external cohorts and to evaluate its clinical utility. Disclaimer: The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance, and do not necessarily represent the views of the ACR, NIH, (UK) NHS, NIHR, or the department of Health.References:[1]Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. 2020;24(1):516.[2]Wu C, Chen X, Cai Y, et al. JAMA Intern Med. 2020;180(7):934-943.Acknowledgements:The COVID-19 Global Rheumatology Alliance.Disclosure of Interests:Zara Izadi: None declared, Milena Gianfrancesco: None declared, Kimme Hyrich Speakers bureau: Abbvie and grant income from BMS, UCB, and Pfizer, all unrelated to this study., Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, Pfizer, outside the submitted work., Grant/research support from: A consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB) supporting the German RABBIT register., Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB., Grant/research support from: Lilly, Mylan, Pfizer, all unrelated to this study., Loreto Carmona Consultant of: Loreto Carmona’s institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis, Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma., Elsa Mateus Grant/research support from: LPCDR received grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA and Pfizer., Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Lindsay Jacobsohn: None declared, Patti Katz: None declared, Samar Al Emadi: None declared, Leanna Wise: None declared, Emily Gilbert: None declared, Maria Valenzuela-Almada: None declared, Ali Duarte-Garcia: None declared, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum unrelated to this work., Grant/research support from: Amgen and Bristol-Myers Squibb., Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Suleman Bhana Employee of: Suleman Bhana reports non-branded marketing campaigns for Novartis (

Golf is growing in popularity, with some 20 million players predicted to be playing in China alone by 2020.1 Its inclusion as an Olympic sport will only serve to increase the sport's international profile and popularity. At the pinnacle of the sport is a small group of elite professional golfers who, when compared with amateurs, have more reproducible swing mechanics, and generate greater forces and increased repetitive loads, which are thought to result in differing injury rates and patterns from those of the amateur.2 A study carried out by Hawkes et al 3 on professional golfers reported that the majority of injuries were in the leading wrist, with ulnar-sided injury most common. This article will review the biomechanics, clinical presentation and imaging findings in the commonest wrist injuries encountered by the examining sports physician in the elite golfer. We classify these wrist injuries by the anatomical localisation of symptoms; ulnar-sided, radial-sided and dorsal injuries will be described. The reader is also encouraged to review the YouTube video on wrist examination.4 The wrists link the body to the golf club and form the final component of a kinetic chain—composed of the hips, spine and shoulders—which powers and controls the golf swing. The lead side of the body is generally viewed as being more active during the golf swing, providing power to the golf swing; as a result, it is generally more prone to injury. A detailed analysis of wrist biomechanics during the golf swing is beyond the scope of this paper, and this work has already been described several times previously.5–7 An overview of wrist movement through the swing does, however, provide a useful framework on which to consider pathology. The lead (or non-dominant wrist) begins the golf swing in a position of ulnar deviation when addressing …

We thank Carbillon et al for their correspondence.1 The use of hydroxychloroquine (HCQ) in pregnant women with systemic lupus erythematosus (SLE) is not controversial.2 3 Similar to its primary role in the prophylaxis and treatment of SLE, discontinuation of HCQ in pregnancy has been linked to increased disease activity and glucocorticoid use in women with lupus.4–6 Given its benefit and preferable safety profile, the continuation of baseline HCQ therapy in pregnant women with lupus is recommended to maintain disease remission,2 3 regardless of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status. In contrast, there is currently no evidence to suggest that baseline use of HCQ in pregnant women with lupus is protective of SARS-CoV-2 infection or severe COVID-19. The authors adequately summarise our findings …

Groin pain in athletes is a priority area for sports physiotherapy and sports medicine research. Heterogeneous studies with low methodological quality dominate research related to groin pain in athletes. Low-quality studies undermine the external validity of research findings and limit the ability to generalise findings to the target patient population. Minimum reporting standards for research on groin pain in athletes are overdue. We propose a set of minimum reporting standards based on best available evidence to be utilised in future research on groin pain in athletes. Minimum reporting standards are provided in relation to: (1) study methodology, (2) study participants and injury history, (3) clinical examination, (4) clinical assessment and (5) radiology. Adherence to these minimum reporting standards will strengthen the quality and transparency of research conducted on groin pain in athletes. This will allow an easier comparison of outcomes across studies in the future.

Introduction Methods for improving patient safety are predicated on cooperation between healthcare groups, but are the views of health professionals involved in promoting safety shared by other healthcare workforce staff and managers? Aim To compare patient-safety suggestions from health workforce managerial and staff groups with those of patient-safety specialists. Method Samples of managers (424) and staff (1214) in the South Australian state health system and 131 Australian patient-safety specialists were asked to write suggestions for improving patient safety. Group responses were content analysed and compared. Results Patient-safety specialists (83.2%) were more likely to make suggestions than were workforce managers (57.8%) or staff (44.1%). Workforce members from clinical professions were more likely than non-clinicians to tender suggestions. No relationship existed between the importance specialists and managers (ρ=−0.062, p=0.880) and specialists and staff (ρ=−0.046, p=0.912) attached to nine categories of suggestions. There was a high correlation between the importance that managers and non-managers attached to safety strategies (ρ=0.817, p=0.011). Among those who made suggestions, specialists were more likely to suggest implementing reviews and guidelines, and incident reporting. Workforce groups were more likely to recommend increased and improved staffing and staffing conditions, and better equipment and infrastructure. There were no significant differences in the proportions of group members recommending: improving management and leadership; increasing staff safety education and supervision; communication and teamwork; improved patient focus; or tackling specific safety projects. Implications Differences between safety specialists' and workforce groups' beliefs about how to improve patient safety may impede the successful implementation of patient-safety programmes.

Aims: To determine whether indications for ordering antineutrophil cytoplasmic antibodies (ANCA) meet the 1999 guidelines proposed for ANCA testing; and to examine the test characteristics of the ANCA test. Methods: The indications for all ANCA tests over a two-year period were assessed and compared to the 1999 guidelines for the appropriate testing of ANCA. Results: 1127 tests were examined. Overall 33.4% had an indication meeting the 1999 guidelines. The commonest non-guideline indications were ocular or orbital inflammation, liver disease and inflammatory bowel disease. All tests with a positive ANCA had indications for testing in line with the 1999 guidelines. In all but one case an ANCA associated small vessel vasculitis (AASVV) was present. Conclusions: ANCA is ordered for a wide range of guideline and non-guideline indications. No cases of AASVV would have been missed if ordering were restricted to tests meeting the 1999 guidelines.

Background Colonoscopic, endoscopic, and histological studies have demonstrated that intestinal inflammation, similar to the ileo-colitis seen in Crohn9s disease (CD), is a common feature of ankylosing spondylitis (AS). More recently, the existence of a shared genetic basis to CD and AS has been demonstrated [1,2]. Objectives To test whether the association of known CD risk loci with AS is primarily due to the presence of bowel inflammation in AS patients. Methods 286 Caucasian patients fulfilling the modified New York criteria for AS and with no history of inflammatory bowel disease were assessed non-invasively for bowel inflammation using faecal calprotectin and the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ) [3]. All patients and 568 matched healthy controls were genotyped with TaqMan® SNP genotyping assays for the confirmed CD risk loci [2], 1q32 (rs11584383), JAK2 (rs10758669), CDKAL1 (rs6908425), IL12B (rs100454310), ZPBP2 (rs2872507), MUC19/LRRK2 (rs11175593), STAT3 (rs744166), and IL23R (rs1343151, rs10489630, rs11209026). Chi square testing was used to test for association. Results Minor alleles of 1q32 SNP rs11584383 (p=0.002, OR=0.69, 95% CI 0.55–0.87), and IL23R SNPs rs11209026 (p=0.011, OR=0.53, 95% CI 0.32–0.87) and rs1343151 (p=0.027, OR=0.77, 95% CI 0.61–0.97) all conferred protection against AS. However, only the association of 1q32 SNP rs11584383 remained significant after Bonferroni correction for multiple testing (p=0.02). The Cochran9s Q test found no significant difference between ORs after stratification of AS patients by DISQ score and faecal calprotectin (P difference >0.09). Conclusions Previously, the association of CD risk loci with susceptibility to AS has been attributed to the co-occurrence of asymptomatic intestinal inflammation which is well recognised and supports the concept that CD and AS are two extremes of a related genetic and phenotypic disease spectrum. However, our study provides preliminary evidence that the association of the confirmed CD risk locus 1q32 SNP rs11584383 with AS is independent of bowel inflammation. References Parkes M, et al. 2013. Nature reviews Genetics. 14(9):661–673. Danoy P et al. 2010. PLoS genetics. 6(12):e1001195. Stebbings S et al. 2012. Rheumatology. 51(5):858–865. Disclosure of Interest None declared

Objective To quantify the risk of hypoglycaemia associated with the concomitant use of dipeptidyl peptidase-4 (DPP-4) inhibitors and sulphonylureas compared with placebo and sulphonylureas. Design Systematic review and meta-analysis. Data sources Medline, ISI Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, and clinicaltrial.gov were searched without any language restriction. Study selection Placebo controlled randomised trials comprising at least 50 participants with type 2 diabetes treated with DPP-4 inhibitors and sulphonylureas. Review methods Risk of bias in each trial was assessed using the Cochrane Collaboration tool. The risk ratio of hypoglycaemia with 95% confidence intervals was computed for each study and then pooled using fixed effect models (Mantel Haenszel method) or random effect models, when appropriate. Subgroup analyses were also performed (eg, dose of DPP-4 inhibitors). The number needed to harm (NNH) was estimated according to treatment duration. Results 10 studies were included, representing a total of 6546 participants (4020 received DPP-4 inhibitors plus sulphonylureas, 2526 placebo plus sulphonylureas). The risk ratio of hypoglycaemia was 1.52 (95% confidence interval 1.29 to 1.80). The NNH was 17 (95% confidence interval 11 to 30) for a treatment duration of six months or less, 15 (9 to 26) for 6.1 to 12 months, and 8 (5 to 15) for more than one year. In subgroup analysis, no difference was found between full and low doses of DPP-4 inhibitors: the risk ratio related to full dose DPP-4 inhibitors was 1.66 (1.34 to 2.06), whereas the increased risk ratio related to low dose DPP-4 inhibitors did not reach statistical significance (1.33, 0.92 to 1.94). Conclusions Addition of DPP-4 inhibitors to sulphonylurea to treat people with type 2 diabetes is associated with a 50% increased risk of hypoglycaemia and to one excess case of hypoglycaemia for every 17 patients in the first six months of treatment. This highlights the need to respect recommendations for a decrease in sulphonylureas dose when initiating DPP-4 inhibitors and to assess the effectiveness of this risk minimisation strategy.

Background Ankylosing spondylitis is a common chronic immune-mediated arthropathy affecting primarily joints of the spine and pelvis. The condition is strongly associated with HLA-B27, and association with other HLA variants has been demonstrated. In addition to these effects, to date 30 non-MHC loci have been associated with the disease, and significant additional heritability remains. Objectives To identify further genetic variants associated with ankylosing spondylitis. Methods We undertook a study of ankylosing spondylitis using 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. This assays all coding variation in the genome along with genomewide association hits and major histocompatibility tag single nucleotide polymorphisms. Analysis was carried out with logistic regression using principal component analysis to correct for any population stratification. Results Novel associations achieving genomewide significance were found in USP8 ( P =3.5 x 10 -52 , OR =1.97) and CDKAL1 ( P =1.8 x10 -8 , OR =1.18). Suggestive associations with common variants in FAM118A ( P =5.9 x 10 -8 , OR =1.16), C7orf72 ( P =1.9 x 10 -7 , OR =1.14) and FAM114A1 ( P =1.4 x 10 -6 , OR =1.14) were also found. A low frequency association (MAF cases/controls: 0.0044/0.0017) was found in patatin-like phospholipase domain containing 1 ( PNPLA1) at a suggestive level of significance ( P =1.5 x 10 -6 , OR =2.6). Conclusions This study describes novel genetic associations with ankylosing spondylitis. Three of the variants have been previously associated with inflammatory bowel disease, and one variant with low hip bone mineral density. These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having very similar aetiopathogenesis. Disclosure of Interest None declared

Background Treatment with TNFα inhibitors has been shown to be effective in improving disease activity and functional capacity in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Evidence indicates that clinical response to anti-TNFα agents tends to be enhanced in nr-axSpA patients with magnetic resonance imaging (MRI)-documented sacroiliac (SI) joint inflammation and elevated C-reactive protein (CRP). Objectives To determine if MRI sacroiliitis positivity and/or elevated CRP at baseline are predictive or associated with changes in measures of disease activity following etanercept (ETN) treatment in patients with nr-axSpA. Methods Patients with symptom duration >3 mths– 3 mg/L. Results A total of 200 subjects (ETN, n=95; PBO, n=105) were included in these analyses. At baseline, breakdown according to MRI sacroiliitis and CRP status was: MRI-/CRP-, n=38; MRI+/CRP-, n=74; MRI-/CRP+, n=21; MRI+/CRP+, n=67. At Week 12, the primary endpoint of ASAS40 was achieved by more patients receiving ETN than those receiving PBO irrespective of MRI/CRP status at baseline (Table). The greatest ASAS40 response was observed in patients with MRI+/CRP+ at baseline and the lowest response was seen in the MRI-/CRP- subgroup. Similar observations were made for all other clinical endpoints with a markedly higher proportion of MRI+/CRP+ patients achieving ASAS20, BASDAI50 and clinically important improvements (Δ≥1.1) in ASDAS-CRP/ESR than those in the other MRI/CRP subgroups. Conclusions Our findings, in patients with early, active nr-axSpA and an inadequate response to ≥2 NSAIDs, are consistent with the hypothesis that a combination of MRI positivity and elevated hsCRP at baseline has a positive predictive value on the SI joint inflammation score and a better clinical response to ETN. A larger sample size is required to test this definitively. Disclosure of Interest M. Brown Grant/research support from: Abbvie, Pfizer, UCB, Wyeth, Leo Pharma, NIAMS, NHMRC, Arthritis Australia, Qld Government, Consultant for: Pfizer, Abbvie, UCB, Speakers bureau: Pfizer, Abbvie, UCB, P. Bird Speakers bureau: Pfizer, Abbvie, Roche, Janssen, BMS, P. Robinson Grant/research support from: NHMRC, ARA, RACP, Consultant for: Pfizer, UCB, Abbvie, Janssen, Menarini, Speakers bureau: Menarini, Janssen, Abbvie, UCB, P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB, F. van den Bosch Consultant for: Abbvie, Celgene, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Janssen, Novartis, Pfizer, UCB, C. Surian Employee of: Pfizer, Z. Wiid Employee of: Pfizer, H. Jones Employee of: Pfizer, A. Szumski Consultant for: Employee of inVentiv Health and was contracted by Pfizer Inc. to provide statistical support, L. Marshall Employee of: Pfizer

We have previously reported that colorectal cancer (CRC) liver metastases from patients, who had received the selective cyclooxygenase 2 (COX-2) inhibitor rofecoxib (Vioxx) 25 mg daily for a mean period of 26 days, had a 31% lower mean microvessel density compared with tumours from individuals who had received placebo only.1 These data suggest that one mechanism of action of rofecoxib in human CRC liver metastases might be inhibition of angiogenesis. Therefore, we investigated the potential antiangiogenic activity of rofecoxib in human CRC liver metastases by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), before and after treatment with oral rofecoxib 25 mg daily for 28 days. As short term treatment of rats with the selective COX-2 inhibitor celecoxib is associated with an increase in serum levels of the endogenous antiangiogenic factor endostatin,2 we also measured serum levels of endostatin and the proangiogenic factor vascular endothelial growth factor (VEGF), at the same time as DCE-MRI. Patients undergoing liver resection of CRC liver metastases were enrolled if diagnostic MRI identified a single metastasis greater than 1.5 cm …

David Norman Howell Owen’s retirement in 1990 brought to an end 175 years of continuous practice by five generations of the Owen family in Fishguard. David’s grandfather established a 10-bedded cottage hospital in Fishguard, and his father developed a radiological service behind the family …