Leg ulceration and ethnicity: a study in west London

Little is known of the influence race has on the development of leg ulceration, with most studies being performed in almost exclusively white populations. As part of a wider audit of leg ulcer services, health care professionals were contacted to give details of age, sex and ethnic background of all patients who attended for treatment of leg ulceration over a one year period in an area of west London. West London Health Care Trust provides services to a population of 275000 of whom 53000 have an ethnic background from the Indian subcontinent (South Asian).In all, 280 patients were identified, of whom 264 (94%) had details of age and sex. This gave a crude ascertainment rate of 1.02 per 1000 population. Of the 264 patients, five were classified as South Asians, with one patient classified as Afro-caribbean. The Mantel Haenzsel test demonstrated a significantly higher proportion of whites suffering from leg ulceration than South Asians, giving an odds ratio of 4.43, with 95% confidence intervals between 1.94 and 10.13 (P=0.0004). The expected frequency of South Asian patients should be 23, based on rates from the white population, of which 13 would be women and 10 men. Only five South Asian men were identified, and no Asian women with leg ulceration.Reasons for this low ascertainment are two-fold. Either there is a real difference between the white and South Asian populations, or South Asian patients are not presenting for treatment. Further work must be performed to determine whether this is an effect of low prevalence, or unmet need in the community.     

Spinal metastases mimicking low back pain of mechanical origin: a case report

Spinal malignancies are an essential consideration when a patient presents to a chiropractic office with back pain. This single case report exemplifies the importance of patient presentation and physical examination findings. We must also consider the rationale for x-raying patients on an individual case basis. Textbook cases do not always exist and special diagnostic tests do not always provide a definitive diagnosis of underlying pathology. Even though history and examination findings suggest a routine diagnosis, continual re-evaluation and recognition of the need to change the diagnosis on occasion is extremely important. The patient should not only be thoroughly evaluated upon initial presentation, but also each time they present for treatment. The decision to x-ray a patient is considered important. X-ray examination can be used to confirm a diagnosis or to rule out potential pathologies, and not necessarily done as a routine screening procedure.A case report is presented in which the pathologic signs were not evident on plain film x-rays upon initial presentation.     

Optic disc haemorrhages and vascular abnormalities in a glaucoma population

Purpose: To retrospectively examine the optic disc photographs of a glaucoma population for optic disc haemorrhages, vascular occlusions and vascular abnormalities. Methods: The optic disc photographs of 906 eyes of glaucoma and suspect glaucoma patients were examined. Optic disc photographs were taken annually, where possible, with the follow-up period varying between 1 and 14 years duration (mean, 2.89). Glaucoma patients are regularly reviewed every 4–6 months and glaucoma suspects every 1–2 years, depending on the ophthalmologist. Low-tension glaucoma patients were reviewed more frequently (mean, every 2.6 months). The results of the findings were compared to a control group of 39 subjects with a mean follow-up period of 7 years, using Fisher's exact test. Results: It was found that during the period under review, 7.4% (n= 67) of eyes had optic disc haemorrhages. The highest frequency of optic disc haemorrhages (37.5%) was found in the low tension glaucoma group (P= 0.0001) followed by 11.4% of primary open-angle glaucoma eyes (P= 0.03). In the normal group there were three eyes with optic disc haemorrhages and one with a disc collateral, which constitutes 5.1% vascular changes in this sub-group. Of the study eyes 2.8% had central retinal vein occlusions, 1.3% branch vein occlusion, 1.2% disc vessel abnormalities (loops) and 1.1% disc collaterals. Discrete nerve fibre layer haemorrhages and microaneurysms were found in 0.8% and 1.8% of eyes, respectively. Conclusions: A total of 16.8% of the eyes observed in this study had either disc haemorrhages or vascular changes. The underlying trend of vascular and haemorrhagic changes in glaucoma are demonstrated in this sample, which is in general agreement with previous studies. The high percentage of optic disc haemorrhages in low tension glaucoma is highlighted. The presence of microaneurysms and nerve fibre layer haemorrhages is interesting but of unknown significance.     

Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics

The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-merrcaptobenzoate-arginine-glycine-aspartate -2-mercaptoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular diehroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.     

Causal association in pharmacovigilance and pharmacoepidemiology: thoughts on the application of the Austin Bradford-Hill criteria.

The methods used for the evaluation of drug safety signals (including major signals leading to withdrawal of products from the market) are inconsistent and sometimes of poor quality. While the assessment of the safety of medicines needs to consider specific issues such as drug interactions and variation in compliance, the general principles, which are used to study environmental hazards, can be applied for this purpose. The criteria proposed by Sir Austin Bradford-Hill more than 35 years ago for attributing disease causation to environmental factors have been used widely in epidemiology, are applicable to pharmacovigilance and pharmacoepidemiology. The Austin Bradford-Hill criteria include strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experimental evidence and analogy. The paper reviews each of these criteria with emphasis on pharmacovigilance and pharmacoepidemiology and with some examples. The application of the Austin Bradford-Hill criteria to the evaluation of causal association in pharmacovigilance and pharmacoepidemiology is very useful. However, it requires understanding of the limitations of the data, such as, under-reporting, poor quality of information from third parties and misclassification. Further work is required to develop strategies to handle these limitations.