Commentary on "DNA damage response and repair gene alterations are associated with improved survival in patients with platinum-treated advanced urothelial carcinoma."

PURPOSE: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in DNA damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients with diagnosis of locally advanced and metastatic urothelial carcinoma treated with platinum-based chemotherapy who had exon sequencing with the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay were identified. Patients were dichotomized based on the presence/absence of alterations in a panel of 34 DDR genes. DDR alteration status was correlated with clinical outcomes and disease features. RESULTS: One hundred patients were identified, of which 47 harbored alterations in DDR genes. Patients with DDR alterations had improved progression-free survival (9.3 vs. 6.0 months, log-rank P = 0.007) and overall survival (23.7 vs. 13.0 months, log-rank P = 0.006). DDR alterations were also associated with higher number mutations and copy-number alterations. A trend toward positive correlation between DDR status and nodal metastases and inverse correlation with visceral metastases were observed. Different DDR pathways also suggested variable effect on clinical outcomes. CONCLUSIONS: Somatic DDR alteration is associated with improved clinical outcomes in platinum-treated patients with advanced urothelial carcinoma. Once validated, it can improve patient selection for clinical practice and future study enrollment.

An effective system to measure and report quality indicators in acute medical units.

The Society for Acute Medicine has developed a number of clinical quality indicators by which all UK Acute Medicine Units can bench mark their activity. These will help to ensure high quality care for patients, inform the continuing development of acute medical services and demonstrate the positive impact of this new specialty. Prospective collection of these data may be a challenge for many busy units. This paper describes a local solution developed in house in a North East hospital. It demonstrates how the data collected can be analysed to assess the effect of changes in consultant presence on the unit and also time taken for patients to be seen by a doctor. The limitations of the system and potential for future development are considered.

Unusual presentation of adenoid cystic carcinoma of the maxillary antrum.

Unusual presentation of adenoid cystic carcinoma of the maxillary antrum. Adenoid cystic carcinoma (ACC) is a rare tumour which affects mainly the major and accessory salivary glands. It is an aggressive neoplasm characterized by early neural invasion and a high incidence of local recurrence and distant metastases, which may develop years after the initial resection. Surgery followed by radiotherapy seems to be the best treatment. Based on a well-illustrated case of extensive maxillary ACC involving the palate, orbit floor, and pterygo-palatine fossa, we discuss the prognosis and the importance of an early diagnosis of ACC.

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR

Excess mortality in a population with diabetes and the impact of material deprivation: longitudinal, population based study.

OBJECTIVES: To establish the age and sex specific mortality for people with diabetes in comparison with local and national background populations; to investigate the relationship between mortality and material deprivation in an unselected population with diabetes. DESIGN: Longitudinal study, using a population based district diabetes register. SETTING: South Tees, United Kingdom. PARTICIPANTS: All people known to have diabetes living in Middlesbrough and Redcar and Cleveland local authorities on 1 January 1994. MAIN OUTCOME MEASURE: Death, from any cause, between 1 January 1994 and 31 December 1999. RESULTS: Over the six years of the study 1205 (24.9%) of 4842 participants died. All cause standardised mortality ratios for type 1 diabetes were 641 (95% confidence interval 406 to 962) in women and 294 (200 to 418) in men, and those for type 2 diabetes were 160 (147 to 174) in women and 141 (130 to 152) in men. Cause specific standardised mortality ratios were increased for ischaemic heart disease, cerebrovascular disease, and renal disease; no reductions in mortality from other causes were seen. The risk of premature death increased significantly with increasing material deprivation (P<0.001). CONCLUSIONS: Diabetes is associated with excess mortality, even in an area with high background death rates from cardiovascular disease. This excess mortality is evident in all age groups, most pronounced in young people with type 1 diabetes, and exacerbated by material deprivation. Aggressive approaches to the management of cardiovascular risk factors could reduce the excess mortality in people with diabetes.

Resolution of lipohypertrophy following change of short-acting insulin to insulin lispro (Humalog).

Lipohypertrophy as a local complication of insulin therapy is well recognized. Despite improvements in insulin purity and the introduction of recombinant human insulin its prevalence has remained high. Rotation of injection sites can reduce the frequency of the problem but does not abolish it. The importance of this complication is not only cosmetic but also in its impact on insulin absorption, and hence glycaemic control. We report a patient who had intractable lipohypertrophy with human recombinant insulin but experienced no such problem when converted onto the insulin analogue lispro. We suggest that the faster speed of absorption of insulin lispro may lead to less hypertrophic stimulation of subcutaneous adipocytes. This difference may be clinically useful in susceptible individuals.

Definition of nursing: 2.

In the first article of this two-part series, Nancy Roper attempted to answer the question 'What is nursing?' by recollecting past experiences that have formed her view. In this article, she continues her quest by examining current developments in practice and education.

Definition of nursing: 1.

A definitive description of nursing has always seemed to elude nurse theorists. Roper's nursing model based on the Activities of Living has played a key role in defining and developing nursing over the past two decades. In this article, the first in a two-part series, Nancy Roper recollects past experiences that have formed her view of nursing.

Resistance of Libyostrongylus douglassi in ostriches to levamisole.

While fenbendazole at 15 mg kg-1 either alone or in combination with resorantel reduced the total burden of Libyostrongylus douglassi by more than 98%, levamisole alone at 30 mg kg-1 was only 28% effective, and in combination with resorantel its efficacy was 67%. These results with levamisole do not correspond with the registered rate of efficacy which is given as at least 80% in South Africa. This is apparently the first reported case of anthelmintic resistance in ostriches.

The anthelmintic efficacy of resorantel against cestodes in sheep.

The anthelmintic efficacy of resorantel against Thysaniezia giardi and Avitellina spp. was tested in sheep at a dosage rate of 65 mg kg-1 live mass. The reduction obtained was 100% in at least 80% of the treated flock.

The anthelmintic efficacy of resorantel against Houttuynia struthionis in ostriches.

Resorantel at a dosage rate of 130 mg kg-1 live body mass was found to be highly effective against Houttuynia struthionis in ostriches when dosed alone or in combination with fenbendazole or levamisole.

The efficacy of fenbendazole at a dosage rate of 5 mg/kg against Dictyocaulus viviparus.

Fenbendazole, dosed to artificially infested cattle at 5 mg/kg live mass, was more than 60% effective in more than 60% of the treated animals against 1-7 day-old Dictyocaulus viviparus larvae reducing the worm load by 87%. It was more than 80% effective in more than 80% of the treated animals against 8-21 day-old worms and 21-34 day-old worms and reduced the worm burdens by 99% in both cases.

The efficacy of fenbendazole at a dosage rate of 5 mg/kg against the third and fourth stage larvae of Dictyocaulus filaria in sheep.

Fenbendazole, dosed to experimentally infested sheep at 5 mg/kg live mass, against immature Dictyocaulus filaria, was more than 80% effective in more than 80% of the animals.