Management of systemic sclerosis: British Society for Rheumatology guideline scope.

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation.

Correction to: The incidence, prevalence, and survival of systemic sclerosis in the UK Clinical Practice Research Datalink.

The above article originally published with an error present in the 2nd sentence in the 4th paragraph of the discussion section and is now presented correctly in this article. The remainder of the article remains unchanged.

Long-term outcomes of daily oral vs. pulsed intravenous cyclophosphamide in a non-trial setting in ANCA-associated vasculitis.

We aimed to compare risk of death, relapse, neutropenia and infection requiring hospital admission between unselected ANCA-associated vasculitis (AAV) patients according to whether cyclophosphamide induction was by daily oral (PO) or pulse intravenous (IV) route. We identified all newly diagnosed AAV patients treated with PO or IV cyclophosphamide between March 2007 and June 2013. We used Cox and logistic regression models to compare mortality, relapse and adverse events and adjusted these for age, renal function and other significant confounders. Fifty-seven patients received PO and 57 received IV cyclophosphamide. One-year survival was 86.0% in PO and 98.2% in IV patients; all-time adjusted hazard ratio (HR) for PO compared to that of IV cyclophosphamide was 1.8 (95% CI 0.3-10.6, P = 0.54). One-year relapse-free survival was 80.7% in PO compared to 87.3% in IV patients, all-time adjusted HR 3.8 (0.2-846, P = 0.37). During the first 12 months, neutropenia of ≤ 0.5 × 109/L occurred in 9 (16%) PO and 0 (0%) IV cyclophosphamide patients (P = 0.003). The number of patients admitted with one or more infections was 16 (28%) in the PO group and 9 (16%) in the IV group, adjusted OR 2.2 (0.6-8.6, P = 0.23). We observed an increased risk of neutropenia, a trend towards increased risk of death and an admission with infection with PO cyclophosphamide. This adds certainty to previous studies, indicating that PO administration induces greater marrow toxicity. Infection-related admissions within 12 months of starting cyclophosphamide were higher than those in clinical trials, possibly reflecting the unselected nature of this cohort.

The incidence, prevalence, and survival of systemic sclerosis in the UK Clinical Practice Research Datalink.

To estimate the incidence, prevalence, and survival of systemic sclerosis in the United Kingdom. We conducted a historical cohort study using data from the Clinical Practice Research Datalink (CPRD). We calculated the incidence and survival of systemic sclerosis between 1994 and 2013 and examined its association with age, sex, and socioeconomic status. We calculated point prevalence on 1 July 2013 and examined its association with the same exposures. We identified 1327 cases with incident systemic sclerosis. Annual incidence was 19.4 per million person-years between 1994 and 2013. The incidence was 4.7 times higher in women than in men, was not influenced by socioeconomic status, and has remained stable over the 20 year study period. The peak age of onset was 55-69 years. Survival at 1, 5, and 10 years was 94.2, 80.0, and 65.7%, respectively. The prevalence was 307 (290-323) per million with the highest prevalence in the 70-84 years age group. We estimate there are currently 1180 new cases of systemic sclerosis each year in the UK, and 19,390 people living with systemic sclerosis. Due to the predicted growth and aging of the population, we predict a 24% increase in incident cases and 26% increase in prevalent cases in 20 years' time. Our estimates of incidence and prevalence are higher than previously reported in the UK, but similar to recent USA and Swedish studies, and do not support a north-south gradient of the occurrence of systemic sclerosis in Europe.

Impacts of anthropogenic activity on the ecology of class 1 integrons and integron-associated genes in the environment.

The impact of human activity on the selection for antibiotic resistance in the environment is largely unknown, although considerable amounts of antibiotics are introduced through domestic wastewater and farm animal waste. Selection for resistance may occur by exposure to antibiotic residues or by co-selection for mobile genetic elements (MGEs) which carry genes of varying activity. Class 1 integrons are genetic elements that carry antibiotic and quaternary ammonium compound (QAC) resistance genes that confer resistance to detergents and biocides. This study aimed to investigate the prevalence and diversity of class 1 integron and integron-associated QAC resistance genes in bacteria associated with industrial waste, sewage sludge and pig slurry. We show that prevalence of class 1 integrons is higher in bacteria exposed to detergents and/or antibiotic residues, specifically in sewage sludge and pig slurry compared with agricultural soils to which these waste products are amended. We also show that QAC resistance genes are more prevalent in the presence of detergents. Studies of class 1 integron prevalence in sewage sludge amended soil showed measurable differences compared with controls. Insertion sequence elements were discovered in integrons from QAC contaminated sediment, acting as powerful promoters likely to upregulate cassette gene expression. On the basis of this data, >1 × 10(19) bacteria carrying class 1 integrons enter the United Kingdom environment by disposal of sewage sludge each year.