Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study.

OBJECTIVES: The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. METHODS: We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. RESULTS: A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. CONCLUSION: This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.

Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis.

OBJECTIVES: We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease. METHODS: Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated. RESULTS: Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-α therapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs. CONCLUSIONS: We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.

Predicting success in graduate entry medical students undertaking a graduate entry medical program.

BACKGROUND: Success in undergraduate medical courses in the UK can be predicted by school exit examination (A level) grades. There are no documented predictors of success in UK graduate entry medicine (GEM) courses. This study looks at the examination performance of GEM students to identify factors which may predict success; of particular interest was A level score. METHODS: Data was collected for students graduating in 2004, 2005 and 2006, including demographic details (age and gender), details of previous academic achievement (A level total score and prior degree) and examination results at several points during the degree course. RESULTS: Study group comprised 285 students. Statistical analyses identified no significant variables when looking at clinical examinations. Analysis of pass/fail data for written examinations showed no relationship with A level score. However, both percentage data for the final written examination and the analysis of the award of honours showed A level scores of AAB or higher were associated with better performance (p<0.001). DISCUSSION: A prime objective of introducing GEM programs was to diversify admissions to medical school. In trying to achieve this, medical schools have changed selection criteria. The findings in this study justify this by proving that A level score was not associated with success in either clinical examinations or passing written examinations. Despite this, very high achievements at A level do predict high achievement during medical school. CONCLUSIONS: This study shows that selecting graduate medical students with the basic requirement of an upper-second class honours degree is justifiable and does not disadvantage students who may not have achieved high scores in school leaver examinations.

Comparing the performance of graduate-entry and school-leaver medical students.

OBJECTIVES: Between 2000 and 2006 Leicester-Warwick Medical Schools (LWMS) provided parallel courses for graduate and school-leaver entrants into medicine. The parallel courses were based upon a single curriculum with ;identical teaching programmes and assessment methods over the two sites (Warwick and Leicester). Warwick runs the curriculum over an accelerated 4-year period for its graduate-entry students. LWMS hence provides a unique opportunity to compare outcomes for these two contrasting groups of students. METHODS: We carried out an observational, quantitative cohort study over a 6-year period covering three cohorts of students who graduated in 2004, 2005 and 2006, respectively, using examination scores as outcome measures. We compared the examination performance of school-leaver and graduate-entry students in written and clinical examinations. These included intermediate clinical examinations, final clinical and final written examinations for both sets of students. Examination data were collected from original mark sheets and university databases at Warwick and Leicester. A-level data were collected from the national University College Admissions Service (UCAS) and compared against examination performance throughout medical school examinations. RESULTS: Graduate-entry students performed as well as school-leaver students prior to entering the full-time clinical element of the course despite having significantly lower A-level grades. School-leaver entrants performed better on midpoint examinations, but had lost this advantage by the time they sat final professional examinations. CONCLUSIONS: This is the first large-scale UK study to compare the performance of graduate-entry and school-leaver medical students following the same clinical curriculum and using the same assessments. Graduate-entry students performed as well as undergraduates in final examinations despite lower A-level grades and a shorter 4-year accelerated course.