Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Petrifying attachments: fear and safety in Jeanette Winterson's tanglewreck and the battle of the sun

This article focuses on Jeanette Winterson's two most extended works of fiction for children, Tanglewreck and The Battle of the Sun, identifying them as narratives of longing and adventure engaging directly with questions of childhood fear and safety. In 2007 I wrote an article on Winterson's adult fiction which focused on her use of vertical imagery. Using such vertiginous drops, I argued, Winterson explores the perilous opportunities afforded by disengaging from a woman-centred storytelling tradition, thus enabling her to 'go it alone'. In Tanglewreck and The Battle of the Sun, these vertical images return and are again connected with questions of attachment and disengagement, yet now with an increasingly overt agenda of negotiating maternal separation anxiety. In Winterson's 2011 memoir, Why Be Happy When You Could Be Normal?, the journey of the first-person narrator, as she travels from child to adulthood, is shrouded in fears linked to lost origins and a safe sense of belonging. As this article shows, these are also the issues facing Silver and Jack, the child protagonists of Tanglewreck and The Battle of the Sun. © 2013 Edinburgh University Press

Predictors of British Isles Lupus Assessment Group-based outcomes in patients with systemic lupus erythematosus: Analysis from the Systemic Lupus International Collaborating Clinics Inception Cohort

BackgroundWe aimed to identify factors associated with a significant reduction in SLE disease activity over 12 months assessed by the BILAG Index.MethodsIn an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12 months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5 mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models.Results'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use.ConclusionBaseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates