The SINS trial: A randomised controlled trial of excisional surgery versus imiquimod 5% cream for nodular and superficial basal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Basal cell carcinoma is the commonest human cancer. Despite increasing incidence it remains poorly researched. While not life threatening it can cause significant cosmetic disfigurement. Imiquimod, a cream which enhances the body's immune response, may help deal with the number of cases that occur in low-risk sites, especially when good cosmetic results and home use without surgery are needed.</p> <p>This study aims 1. To compare excisional surgery with imiquimod cream for nodular or superficial basal cell carcinoma in low risk sites, with respect to 3 year clinical clearance, cost-effectiveness and cosmetic results. 2. To ascertain if certain phenotypic features and gene polymorphisms predict tumour responsiveness to treatment.</p> <p>Methods/Design</p> <p>Five hundred participants with low risk nodular or superficial basal cell carcinoma will be recruited from hospitals to this multi-centre, randomised, parallel group, controlled phase III trial. Treatment in the imiquimod group is for 6 weeks for superficial basal cell carcinoma and 12 weeks for nodular basal cell carcinoma. Both treatment groups are followed up in clinic for 3 years. Primary outcome variable: the proportion of participants with clinical evidence of success (no recurrence) at 3 years. The primary outcome will be compared between the two treatment groups. Secondary outcomes include: i) clinical success at 1, 2 and 5 years, ii) time to first recurrence, iii) cosmetic appearance of lesion site after treatment, iv) level of pain, and v) cost-effectiveness. Safety and tolerability data will also be reported.</p> <p>Discussion</p> <p>This study protocol describes a pragmatic randomised controlled trial which it is hoped will address the above uncertainties. Three-year results will be available towards the end of 2010.</p> <p>Trial registration</p> <p>Meta-register: NCT00066872, Eudract No. 2004-004506-24, ISRCTN48755084.</p

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

<p>Abstract</p> <p>Background</p> <p>The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. <it>In vitro </it>data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients.</p> <p>Methods</p> <p>We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping.</p> <p>The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test.</p> <p>Results</p> <p>Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls.</p> <p>The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively.</p> <p>Conclusion</p> <p>These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed.</p

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

How reproducible are surface areas calculated from the BET equation?

Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer-Emmett-Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of micro- and mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already-measured raw adsorption isotherms were provided to sixty-one labs, who were asked to calculate the corresponding BET areas. This round-robin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called "BET surface identification" (BETSI), expands on the well-known Rouquerol criteria and makes an unambiguous BET area assignment possible

Skin disease in haemophiliacs with and without antibodies to the human immunodeficiency virus (HIV): further evidence of altered disease behaviour in different risk groups?

Forty-one patients routinely attending the Oxford Haemophilia Centre entered a controlled, blind investigation in order to determine whether HIV antibody status was related to the presence of skin disease. Twenty-four of the 41 patients (58.5%) were HIV antibody positive and none had any general symptoms. Comparison of the HIV antibody positive group with the HIV antibody negative group and with non-haemophiliac controls showed an increased prevalence of four HIV-associated dermatoses: 11 patients had seborrhoeic dermatitis (10 HIV antibody positive and one HIV antibody negative (P less than 0.05 chi 2 test], eight patients had folliculitis (six HIV antibody positive), four patients had mucocutaneous candidiasis, all were HIV antibody positive, and three patients had onychomycosis, all were HIV antibody positive. None of these conditions was seen in a group of 16 non-haemophiliac controls. These findings are different from those reported from a similar study of comparable groups of homosexual men and these results may be further evidence to support the belief that the behaviour of HIV infection differs between haemophiliacs and other risk groups