COVID-19: responding to a pandemic on Operation TORAL.

Operation TORAL was the UK's contribution to NATO's Operation RESOLUTE SUPPORT in Kabul, Afghanistan. Approximately 1000 British troops were deployed in Kabul when the arrival of the COVID-19 pandemic in Afghanistan was declared. This article will describe the challenges faced due to COVID-19 in Kabul.Medical planning considerations, occupational health issues, implementation of behaviour change and operating as part of a multinational organisation are all discussed, with challenges encountered detailed and potential solutions offered. The use of a suggested framework for ensuring the medical estimate process covered all areas relevant to an emerging viral pandemic -the 4Ds and 4Cs approach-proved particularly useful in the early stages of the pandemic in Afghanistan.

Eye Tracking Effort Expenditure and Autonomic Arousal to Social and Circumscribed Interest Stimuli in Autism Spectrum Disorder.

The social communicative deficits and repetitive behaviours seen in Autism Spectrum Disorder (ASD) may be affected by altered stimulus salience and reward attribution. The present study used eye tracking and a behavioural measure to index effort expenditure, arousal, and attention, during viewing of images depicting social scenes and subject-specific circumscribed interests in a group of 10 adults with ASD (mean age 25.4 years) and 19 typically-developing controls (mean age 20.7 years) Split-plot and one-way repeated measures ANOVAs were used to explore results. A significant difference between the ASD and control group was found in the amount of effort expended to view social and circumscribed images. The ASD group also displayed significant differences in pupillary response to social and circumscribed images, indicative of changes in autonomic arousal. Overall, the results support the social motivation hypothesis in ASD (Chevallier et al., Trends Cogn Sci 16(4):231-239, 2012) and suggest a role for autonomic arousal in the ASD symptom dyad.

A novel use of QR code stickers after orthopaedic cast application.

INTRODUCTION We present a novel solution to ensure that information and contact details are always available to patients while in cast. An information sticker containing both telephone numbers and a Quick Response (QR) code is applied to the cast. When scanned with a smartphone, the QR code loads the plaster team's webpage. This contains information and videos about cast care, complications and enhancing recovery. METHODS A sticker was designed and applied to all synthetic casts fitted in our fracture clinic. On cast removal, patients completed a questionnaire about the sticker. A total of 101 patients were surveyed between November 2015 and February 2016. The questionnaire comprised ten binary choice questions. RESULTS The vast majority (97%) of patients had the sticker still on their cast when they returned to clinic for cast removal. Eighty-four per cent of all patients felt reassured by the presence of the QR code sticker. Nine per cent used the contact details on the cast to seek advice. Over half (56%) had a smartphone and a third (33%) of these scanned the QR code. Of those who scanned the code, 95% found the information useful. CONCLUSIONS This study indicates that use of a QR code reassures patients and is an effective tool in the proactive management of potential cast problems. The QR code sticker is now applied to all casts across our trust. In line with NHS England's Five Year Forward View calling for enhanced use of smartphone technology, our trust is continuing to expand its portfolio of patient information accessible via QR codes. Other branches of medicine may benefit from incorporating QR codes as portals to access such information.

Effect of implementation of a preconception counselling resource for women with diabetes: A population based study.

AIM: To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. METHODS: A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n=135), including a viewed-DVD subgroup (n=58), were compared with an historical cohort (pre-DVD, n=114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. RESULTS: Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8mmol/mol]; p=0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8mmol/mol], P<0.001; planned pregnancy (88% vs. 59%, P<0.001); taken folic acid preconception (81% vs. 43%, P=0.001); and had HbA1c recorded preconception (88% vs. 53%, P<0.001) than the pre-DVD cohort. CONCLUSIONS: Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial.

OBJECTIVE: To compare the efficacy of etanercept (ETN) and methotrexate (MTX) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis. METHODS: In a 78-week multicentre randomised placebo-controlled superiority trial, 110 DMARD-naïve patients with early clinical synovitis (≥1 tender and swollen joint, and within 3 months of diagnosis) and either rheumatoid factor, anticitrullinated protein antibodies or shared epitope positive were randomised 1:1 to receive MTX+ETN or MTX+placebo (PBO) for 52 weeks. Injections (ETN or PBO) were stopped in all patients at week 52. In those with no tender or swollen joints (NTSJ) for >26 weeks, injections were stopped early. If patients had NTSJ >12 weeks after stopping the injections, MTX was weaned. The primary endpoint was NTSJ at week 52. RESULTS: No statistically significant difference was seen for the primary endpoint (NTSJ at week 52 (32.5% vs 28.1% [adjusted OR 1.32 (0.56 to 3.09), p=0.522]) in the MTX+ETN and MTX+PBO groups, respectively). The secondary endpoints did not differ between groups at week 52 or 78. Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 (38.5% vs 9.2%, adjusted OR 8.87 (2.53 to 31.17), p=0.001) and week 12 (65.1% vs 43.8%, adjusted OR 2.49 (1.12 to 5.54), p=0.026). CONCLUSIONS: In this group of patients with early inflammatory arthritis, almost a third had no tender, swollen joints after 1 year. MTX+ETN was not superior to MTX monotherapy in achieving this outcome. Clinical responses, however, including DAS28-CRP<2.6, were achieved earlier with MTX+ETN combination therapy. TRIAL REGISTRATION NUMBER: The EMPIRE trial is registered on the following trial registries: Eudract-2005-005467-29; ISRCTN 55428162 (http://www.controlled-trials.com/ISRCTN55428162/EMPIRE). The full trial protocol can be obtained from the corresponding author.

Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study).

OBJECTIVES: In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction. METHODS: In a 78-week multicentre randomised controlled trial, double-blinded to week 26, 112 treatment-naive RA patients (1987 American College of Rheumatology classification criteria) with disease activity score 44 (DAS44)>2.4 were randomised to MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg. A treat-to-target approach was used with treatment escalation if DAS44>2.4. In the IFX group, IFX was discontinued for sustained remission (DAS44<1.6 for 6 months). The primary outcome was change in modified total Sharp-van der Heijde score (mTSS) at week 50. RESULTS: The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units, respectively (adjusted difference (95% CI) -1.45 (-3.35 to 0.45); p=0.132). Radiographic non-progression (mTSS<2.0) occurred in 81% vs 71% (OR 1.77 (0.56 to 5.61); p=0.328). DAS44 remission was achieved at week 50 in 49% and 36% (OR 2.13 (0.91 to 5.00); p=0.082), and at week 78 in 48% and 50% (OR 1.12 (0.47 to 2.68); p=0.792). Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group. Of the IFX group, 25% (14/55) achieved sustained remission and stopped IFX. No substantive differences in adverse events were seen. CONCLUSIONS: In DMARD-naive early RA patients, initial therapy with MTX+high-dose intravenous steroid resulted in good disease control with little structural damage. MTX+IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach.

The novel use of commonly captured data to assess a district's diabetes service that encompasses both primary and secondary care.

AIM: To identify commonly captured data in the UK to look at the performance of a district's diabetes care that encompasses both primary and secondary care. METHODS: Primary care quality outcomes framework (QOF) measures for diabetes, referral rates for first appointment for specialist secondary care and emergency admission rates for diabetes (Dr Foster/HES) were used to produce a performance index scoring system. Illustrative measures from QOF were total diabetes points, DM23 attainment of HbA1c <7% (53 mmol/mol) and its exemption rate (number of patients excluded from analysis). The performance index was used to study the effectiveness of the Medway district diabetes service and this was compared to another district (Guildford) within the same Strategic Health Authority and nationally. RESULTS: Medway has the highest prevalence of Diabetes (6.1%) of the 8 Primary Care Trusts examined, the lowest achievement of diabetes QOF points (96.1%) and the lowest achievement of an HbA1c level <7% (53 mmol/mol) (54.3%). Exemption reporting was the 3rd highest. SAR for first diabetes out-patient appointment to the hospital was low at 281 (predicted 576) 48% of expected. The emergency admission rate was high at 225 (predicted 168) 133% of expected. Thus primary care diabetes needs to raise performance and implement a lower threshold for OPD referral to prevent emergency admissions. CONCLUSION: It is possible to produce an assessment of diabetes care that transcends primary/secondary care that gives a true reflection of a district's performance which will be useful to plan future health service provision.

Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study.

OBJECTIVE: To determine whether the HLA-DRB1 shared epitope (SE) is associated with early mortality and specific causes of death in rheumatoid arthritis (RA). METHODS: HLA-DRB1 genotyping was carried out on blood samples from 767 patients recruited for the Early RA Study (ERAS), a multicenter, inception cohort study with followup over 18 years. Dates and causes of death (n = 186) were obtained from the Office of National Statistics. The association of HLA-DRB1 alleles with risk of mortality was assessed using Cox proportional hazards regression analyses. Multivariate stepwise models were used to assess the predictive value of HLA-DRB1 genotypes compared with other potential baseline risk factors. RESULTS: The SE was not significantly associated with overall mortality. However, the presence of 2 SE alleles was associated with risk of mortality from ischemic heart disease (hazard ratio [HR] 2.02 [95% confidence interval 1.04-3.94], P = 0.04), and malignancy (HR 2.18 [95% confidence interval 1.17-4.08], P = 0.01). Analysis of specific SE genotypes (corrected for age and sex) revealed that the HLA-DRB1*0101/*0401 and 0404/*0404 genotypes were the strongest predictors of mortality from ischemic heart disease (HR 5.11 and HR 7.55, respectively), and DRB1*0101/*0401 showed a possible interaction with smoking. Male sex, erythrocyte sedimentation rate, and Carstairs Deprivation Index were also predictive, but the Health Assessment Questionnaire score, rheumatoid factor, nodules, and swollen joint counts were not. Mortality due to malignancy was particularly associated with DRB1*0101 genotypes. CONCLUSION: The risk of mortality due to ischemic heart disease or cancer in RA is increased in patients carrying HLA-DRB1 genotypes with particular homozygous and compound heterozygous SE combinations.

Is minocycline therapy in acne associated with antineutrophil cytoplasmic antibody positivity? A cross-sectional study.

BACKGROUND: Minocycline (MN), one of the commonly prescribed therapies for acne, is known to be associated with autoimmune disorders including drug-induced lupus. However, data are sparse regarding the prevalence of autoimmune disease in acne or in patients with acne treated with MN. OBJECTIVES: To establish the prevalence of antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA) and new autoimmune syndromes in an MN-exposed and unexposed population with acne. METHODS: In a cross-sectional study, 252 patients with acne vulgaris were assessed. Sixty-nine per cent had been exposed to MN at some point or were taking the drug at the time of the interview. Data recorded included duration of disease (acne) and drug history as well as possible side-effects of drugs, in particular joint symptoms (pain and swelling). In addition, blood was taken for ANA, ANCA, liver function tests and HLA analysis. RESULTS: There was no statistical difference in the prevalence of ANA positivity between patients exposed (13%) or not exposed (11%) to MN. However, higher titres of ANA (1/160 or higher) were found in the MN-exposed group (45% compared with 12% in the unexposed group). ANCA positivity was found in 7% of the MN-exposed group but no positivity was found in the unexposed cohort (P = 0.022). In 58% of cases, the ANCA detected were of the perinuclear pattern (p-ANCA) with myeloperoxidase specificity, and this finding was associated with clinical symptoms in the majority of cases. Two p-ANCA-positive patients were thought in retrospect to have developed a drug-induced lupus syndrome. CONCLUSIONS: ANA positivity is seen in patients with acne irrespective of exposure to MN; however, p-ANCA appear to be a serological marker for developing autoimmune disease in patients receiving MN.

Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis.

OBJECTIVE: To examine the cause of death in a large UK inception cohort of rheumatoid arthritis (RA), and whether this was related to disease duration and severity, treatment effects or extra-articular features and complications of RA. METHODS: Standard clinical, laboratory, radiological and socio-economic measures were recorded at baseline and yearly in an inception cohort started in nine centres in 1986. Date and the cause of death were based on death certificates and the comparisons made with age and sex matched population figures. Risk factors for mortality were identified from baseline measures of disease. RESULTS: There were 459 deaths (32%) in 1429 patients followed for up to 18 yrs. Standard mortality ratio was 1.27. Survival was significantly lower in the first 7 yrs of RA. Excess mortality was seen in cardiovascular disease (31%), pulmonary fibrosis (4%) and lymphoma (2.3%). Baseline predictors for mortality were men, older age, poor function, lower socio-economic status, extra-articular features, comorbidity, rheumatoid factor, X-ray erosions, high-ESR and low-haemoglobin. CONCLUSION: There was a modest increase in mortality in RA, mainly in the first 7 yrs. Deaths from cardiovascular disease and pulmonary fibrosis were higher than expected, but treatment-related deaths were low. Risk factors included less favourable socio-economic status, markers of disease severity and diminished function within the first year.

Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome.

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as highly specific for rheumatoid arthritis (RA). Studies suggest an association with radiographic outcome. The aims of this study were to assess the diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a large cohort of early RA patients compared with connective tissue disease (CTD) controls. METHODS: One hundred and eighty-two patients with RA and 121 patients with CTD were recruited. All RA patients had less than 24 months of symptoms and had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies measured at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months. RESULTS: The anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of 81% for RA when compared with controls. In RF-negative patients, specificity was 92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age 57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive, 81% CCP-positive and 21% erosive. The only predictor of change in Larsen score from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05) and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional response at 24 months (P<0.05). CONCLUSIONS: This study confirms the diagnostic utility of anti-CCP(2) antibodies in early RA, particularly in seronegative patients, in whom anti-CCP(2) positivity also conferred prognostic utility for radiographic and functional outcomes.

Analysis of the insertion/deletion related polymorphism within T cell antigen receptor beta variable genes in primary Sjögren's syndrome.

OBJECTIVE: To analyse T cell receptor beta variable (TCRBV) gene polymorphisms (insertion/deletion related polymorphism (IDRP) and BV6S7) in primary Sjögren's syndrome (PSS). METHODS: Genomic DNA was extracted from blood samples from patients fulfilling the modified European criteria for PSS (n = 61). Healthy control blood samples were obtained from the Blood Transfusion Service (n = 121). As a disease control group, samples from patients with systemic lupus erythematosus (n = 42) were analysed. BV6S7 was genotyped using an established PCR/RFLP method. The IDRP was determined by comparison of the intensity of PCR product bands from within BV9S2 and an internal control region (BV9S1), to ascertain whether 0, 1, or 2 copies of the insertion were present. RESULTS: There was a decrease (p = 0.018) in the proportion of PSS patients with the deleted/deleted genotype. There was no association with specific BV6S7 alleles or genotypes with either the PSS group or the hypergammaglobulinaemic subgroup. There were no significant differences in haplotype frequencies after Bonferroni correction. CONCLUSIONS: A reduced proportion of patients with PSS have the deleted/deleted genotype. Eighty nine per cent of PSS patients have at least one extra germline copy of BV13S2*1. This may relate to previous observations of increased BV13 specific T cells and mRNA in the salivary glands.

Emergency ambulances on the public highway linked with inconvenience and potential danger to road users.

OBJECTIVES: The main aim was to survey interactions between the public highway users and emergency ambulances using lights and sirens. The objectives were to identify negative and positive experiences, and to assess the frequency and consequences of these events. METHODS: Because of a poor response from a random postal pilot, a quota sample of 200 was adopted with a response of 65%. This provided data on demographics, details of previous interactions, and possible third party effects. Participant perception of psychological stress in negative interactions was also recorded. Possible links between the recorded interactions were assessed using the chi(2) tests of association. RESULTS: The passage of an emergency ambulance using lights and sirens caused the public to move from their chosen position in most cases (61%). Horns or sirens were used frequently (86%), but they were not always applied in unison with the warning lights. A significant association was found between the satisfactory handling of events by the ambulance crews and the use of audible warning devices (p<0.001). Twenty per cent of avoidance manoeuvres necessitated reversing, which was associated with a third party affect (p<0.005). Roughly one third of the participants found interactions stressful and felt that the events could have been avoided. Most public road users (91%) believed that they acted in a controlled manner. CONCLUSIONS: The findings suggest that most participants had interacted with the emergency ambulances in a positive manner, while a smaller but significant fraction of the public road users found the interactions difficult to handle. A third party effect was identified in avoidance manoeuvres. Further longitudal research with random sampling is recommended.