Trends in Type 1 diabetes incidence in the UK in 0- to 14-year-olds and in 15- to 34-year-olds, 1991-2008.

AIM: To describe Type 1 diabetes incidence trends in the UK between 1991 and 2008 in children aged 0-14 years and in young adults aged 15-34 years. METHODS: Data from the UK General Practice Research Database were analysed, including 3002 individuals (1565 aged 0-14 years and 1437 aged 15-34 years) newly diagnosed with Type 1 diabetes. Poisson regression was used to model annual incidence increases and seasonality effects. RESULTS: Type 1 diabetes incidence increased from 11 to 24/100,000 person-years in boys and from 15 to 20/100,000 person-years in girls. In adults, the incidence rate increased from 13 to 20/100,000 person-years (men) and from 7 to 10/100,000 person-years (women). Annual incidence increases tended to be greater in children (4.1%, 95% CI 3.0-5.2%) compared with 15- to 34-year-olds (2.8%, 95% CI 1.6-3.9%). There was evidence of higher incidence rates during autumn and winter in children, but not in adults. CONCLUSIONS: A continuing increase in Type 1 diabetes incidence was shown that was greater in children than in young adults. Seasonal variation was observed in children only.

Importance of routine cavity sampling in breast conservation surgery.

BACKGROUND: The role of cavity biopsy (CB) at the time of wide local excision (WLE) for primary breast cancer has not been evaluated fully. This study compared four groups of patients to determine the significance of margins and CB histology on tumour characteristics and outcome. METHODS: This was a retrospective study of patients undergoing WLE and CB in one institution over 21 years. Demographic data, tumour characteristics and survival information were obtained. Four subgroups of patients were compared according to their margin and cavity status (positive or negative). RESULTS: A total of 957 patients had WLE. The median 10-year survival was 85.6 per cent and breast cancer-specific survival was 92.4 per cent. Tumour size, grade, node and oestrogen receptor status were independent predictors of survival. There was poor concordance between positivity of resection margins and CB (32.0 per cent); a negative margin carried a 10.8 per cent risk of demonstrable residual disease. A positive CB, but not a positive margin, was associated with reduced overall survival and breast cancer-specific survival. CONCLUSION: Cavity status was more significant with regard to survival than margin status. CB is important in identifying residual and multifocal disease, as margin and cavity positivity are often not concordant.

Improvements in breast cancer survival over time, related to adjuvant treatment and node status.

BACKGROUND: There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups. METHODS: A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplan-Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis. RESULTS: The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p<0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p<0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p=0.99. Within the node negative group, patients with tumours >or= 2 cm had an improved RFS from 80% to 88%, p=0.02. CONCLUSION: The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal.

The significance of the site of recurrence to subsequent breast cancer survival.

AIM: To investigate differences in the 3-year survival of patients with recurrent breast cancer dependent on recurrence site. METHODS: The study was a review of 294 patients from a breast cancer database, who were treated for operable breast cancer and subsequently developed a recurrence between 1989 and 2003. Patients were divided into four groups according to the site of first recurrence (local, lymph node, bone or visceral). Breast Cancer Specific Survival (BCSS) was compared using Kaplan-Meier life table analysis and the log rank test. RESULTS: Patient and tumour characteristics were comparable between the four groups. Survival rates between the recurrence site groups were significantly different. Patients in whom first recurrence was local had the best prognosis with a 3-year BCSS of 83% compared to 33% for patients with first node recurrence (p<0.001), 23% for patients with first bone recurrence (p=0.03) and 13% for patients with first visceral recurrence (p=0.004). CONCLUSION: Survival of patients with recurrent breast cancer is associated with the site of first recurrence. The prognosis from recurrence is progressively worse with local, regional, bone and visceral metastasis.

Two-week rule: has prioritisation of breast referrals by general practitioners improved?

INTRODUCTION: A 9-month audit, soon after the introduction of the 2-week rule in the UK in 1999, showed that a significant number of breast cancer patients were referred as non-urgent by their GPs, when the goal is that all suspected breast cancer patients should be seen by a hospital specialist urgently within 2 weeks of referral. The aim of this study was to determine whether GP grading of referrals into urgent and non-urgent had improved. METHOD: A retrospective review of GP referrals over 8 months, between September 2003 and April 2004, with regard to their urgency, subsequent diagnosis and the use of proformas (standardised referral formats) was carried out. The results were compared to the 1999 audit. RESULTS: Eighty-two of 1178 patients referred by GP had breast cancer, versus 115 of 1176 patients referred in 1999. Sixty-eight per cent (56/82) of breast cancer patients were referred as urgent, compared to 47% (54/115) in 1999 (P=0.005). A proforma was used in 47% (548/1178) of GP referrals while no proforma was used in 1999. Sixty-five of the 82 cancer patients were referred with a proforma and 85% (55/65) were referred as urgent. CONCLUSION: GP prioritisation of referrals has improved since 1999. With the use of proformas a significant number of patients with cancer were referred urgently.

Synthesis of fluorochromes and pigments in Malassezia furfur by use of tryptophan as the single nitrogen source.

A new minimal medium consisting only of L-tryptophan (L-Trp) and a lipid source induced formation of brown pigmentation only in the species Malassezia furfur, which diffuses into the agar. Strains of the species M. sympodialis and M. pachydermatis failed to grow on this medium. On mDixon medium, however, after replacement of peptone by L-Trp, growth of all three Malassezia species was achieved. Under these conditions pigment production was observed with all M. furfur strains tested, although the results for M. pachydermatis strains were inconsistent. M. sympodialis strains showed no pigment production. On the minimal medium pigmentogenesis was induced in M. furfur by only 0.01 g% tryptophan; the pH optimum was pH 5. In all M. furfur strains, alternative amino nitrogen sources given concurrently with Trp suppressed pigmentogenesis. Furthermore, there were differences in the optimal temperature among the individual M. furfur strains. CBS 7019, CBS 6000 and CBS 6001 failed to produce pigment at 37 degrees C. The extract of the culture exhibited remarkable fluorescence, and several indole derivatives with a broad spectrum of colours were detected. This finding may have an impact on the clinical appearance of pityriasis versicolor, a very common skin disease caused by lipophilic yeasts of the genus Malassezia. We hypothesize that in pityriasis versicolor metabolic adaptation of Malassezia yeasts to altered nitrogen conditions on superficial skin might be of patho-physiological importance. Tryptophan as an inducer of pigmentogenesis probably accumulates during excessive sweating, a well-known manifestation of pityriasis versicolor.

Growth requirements and nitrogen metabolism of Malassezia furfur.

Investigations on the nutrient requirements of Malassezia yeasts led to the preparation of a new minimal medium consisting of an amino nitrogen and a lipid source, which only allowed the growth of the species M. furfur. Carbohydrates, electrolytes, vitamins and trace elements were not required. Using the basal medium, a nitrogen auxanogram for M. furfur was developed, which allowed investigation of the assimilation of 22 amino acids and 9 further nitrogen sources. With the exception of cysteine, all amino acids were metabolized, as were ammonium salts, urea, creatine, creatinine, uric acid and allantoin. KNO3, however, failed to support growth. Depending on the source used, the yeast cells changed micromorphologically: both oval and round forms were induced. Assimilation of several amino acids resulted in dimorphism, especially in the case of glycine and serine. The cell yield differed significantly depending on the nitrogen source; short-chain unbranched amino acids were utilized most readily. Thus, M. furfur can be characterized as a relatively undemanding yeast species which is optimally adapted to the superficial skin environment. All other lipid-dependent Malassezia species seem to require more complex media.