Assuring the quality of interpretative comments in clinical chemistry.

The provision of interpretative advice on laboratory results is a post-analytic activity and an integral part of clinical laboratory services. It is valued by healthcare workers and has the potential to prevent or reduce errors and improve patient outcomes. It is important to ensure that interpretative comments provided by laboratory personnel are of high quality: comments should be patient-focused and answer the implicit or explicit question raised by the requesting clinician. Comment providers need to be adequately trained and qualified and be able to demonstrate their proficiency to provide advice on laboratory reports. External quality assessment (EQA) schemes can play a part in assessing and demonstrating the competence of such laboratory staff and have an important role in their education and continuing professional development. A standard structure is proposed for EQA schemes for interpretative comments in clinical chemistry, which addresses the scope and method of assessment including nomenclature and marking scales. There is a need for evidence that participation in an EQA program for interpretative commenting facilitates improved quality of comments. It is proposed that standardizing goals and methods of assessment as well as nomenclature and marking scales may help accumulate evidence to demonstrate the impact of participation in EQA for interpretative commenting on patient outcome.

Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb.

BACKGROUND: Mutations in the FOXC2 gene cause lymphedema distichiasis, an inherited primary lymphedema in which a significant number of patients have varicose veins. Because lymphedema distichiasis is believed to be caused by lymphatic valve failure (reflux), and FOXC2 is highly expressed on venous valves in mouse embryos, we tested the hypothesis that FOXC2 mutations may be linked to venous valve failure and reflux. METHODS AND RESULTS: The venous system of the leg was investigated with Duplex ultrasound. Pathological reflux was recorded by color Duplex ultrasound in all 18 participants with a FOXC2 mutation, including 3 without lymphedema. Every participant with a mutation in FOXC2 showed reflux in the great saphenous vein (n=18), compared with only 1 of 12 referents (including 10 family members; P<0.0001, Fisher exact test). Deep vein reflux was recorded in 14 of 18 participants. CONCLUSIONS: FOXC2 is the first gene in which mutations have been strongly associated with primary venous valve failure in both the superficial and deep veins in the lower limb. This gene appears to be important for the normal development and maintenance of venous and lymphatic valves.

Lipid external quality assessment: commutability between external quality assessment and clinical specimens.

BACKGROUND: Targets for cholesterol reduction are part of the Quality Outcomes Framework and general practitioners have to meet these targets to fulfil their remuneration package. By contrast, there are no targets for the accuracy of cholesterol or other lipid measurements and no recent surveys on performance of these assays. We have assessed the performance of lipid measurement of the available methods in the UK. METHODS: Serum samples collected from individual donors attending the national blood service were distributed after values were obtained from a secondary reference laboratory. Samples were sent to participant laboratories to assess different methods' analytical performance on single donation specimens, on routine external quality assessment pooled specimens, on specimens subjected to a range of freeze-thaw cycles and on frozen-stored specimens. RESULTS: Differences in measured cholesterol were found that were method-dependent and related to triglyceride content. HDL-cholesterol (HDL-C) showed significant positive bias in all assays. Individual donor specimens showed no significant changes with differing numbers of freeze-thaw cycles. Pooled serum was stable for up to six months. CONCLUSIONS: Most cholesterol measurements are accurate but some methods are affected by triglyceride interference. HDL-C methods show significant positive bias. Although there are potential matrix effects introduced as a result of specimen preparation, additional work is needed to show if these effects are present in fresh patient samples.

Developing effective services for people with COPD.

In terms of health care resources, chronic obstructive pulmonary disease (COPD) has long been the poor relation of other respiratory conditions such as asthma and lung cancer. However, over the last 10 years health professionals have recognised the importance of COPD and its cost to society and have been motivated to provide an improved service for patients. The first guidelines for the management of COPD were published by the British Thoracic Society in 1997. The Global Initiative for Chronic Obstructive Lung Disease followed this document with its Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (2001).

Sarcoma of the bladder with metastasis to the left ventricle.

Genitourinary sarcomas are rare clinical entitities. Current information on these tumours is sparse and anecdotal. Cardiac metastasis from genitourinary tumours in general is an exceedingly rare phenomenon and has previously been reported only in relation to carcinomas. We report the first case of sarcoma of the bladder with metastasis to the heart causing sudden death.

The effects of irrigation fluid on core temperature in endoscopic urological surgery.

AIMS AND METHOD: A prospective observational study of 100 patients undergoing various types of endoscopic urological surgery including transurethral resection of the prostate (TURP), transurethral resection of bladder tumour (TURBT), percutaneous nephrolithotomy (PCNL) and Cystoscopies, was reformed to determine the temperature difference between preoperative and postoperative core temperatures and to determine whether this change was related to the age, weight, type of anaesthetic, operation duration, type of operation, amount of irrigant fluid used and whether warming the fluid to 370C made a difference to the degree of temperature change. All the above variables were recorded for each patient as well as the preoperative and postoperative temperatures. Statistical analysis was carried out using SPSS. RESULTS: The mean age was 64 years and the mean weight was 75kg in the study. Seventy-six patients had a general anaesthetic while 24 had a spinal anaesthetic. The study included 29 TURPs, 10 TURBTs, six PCNLs and 55 Cystoscopies. Age and type of anaesthetic did not correlate significantly with temperature change. As weight increased patients tend to preserve their core temperature more efficiently. The highest degree of temperature drop was in the PCNL group. There was a significant relationship between the duration of operation and temperature drop (p<0.05) as well as the amount of irrigation fluid used (p<0.05). Average temperature drop for patients who underwent irrigation with fluid at room temperature (n=43) was 1.37 degrees C and 0.95 degrees C for those whose fluids were warmed to body temperature (n=57). This difference was statistically significant (p=0.03). CONCLUSIONS: There is a drop in temperature in patients undergoing most endoscopic operations on the GU tract and this appears to be multifactorial in origin, relating significantly to weight, amount of irrigation fluid used, type and duration of operation. Warming irrigant fluid to body temperature appears to significantly reduce the degree of temperature drop with consequent potential benefit.

Bile salt/lecithin mixed micelles optimized for the solubilization of a poorly soluble steroid molecule using statistical experimental design.

Bile salts and lecithin combine physiologically to form mixed micelles which aid the solubilization and absorption of dietary fats and drug molecules. In this series of experiments, we have shown how experimental design procedures aid the optimization of a formulation incorporating a bile salt, lecithin, and water with fluticasone propionate (FP) as the model poorly soluble drug. The initial inclusion of a categorical variable ruled out the use of classic response surface designs; therefore the experimental design was constructed using a d-optimal selection from a candidate set of all possible experimental combinations. A separate 2-factor central composite design was used to determine the optimum lecithin and bile salt concentrations over an extended range after the categorical variable had been eliminated. It has been demonstrated that an increase in either lecithin or cholic acid concentration produces an increase in solubility of FP, while sodium taurocholate appears to depress the solubility of FP compared with the other two bile salts. The increase in solubility associated with the increase in bile salt and lecithin is further demonstrated by a linear relationship between FP solubility and the total lipid in the formulation. The influence of molar ratio of lecithin to bile salt in the formulation is also significant. The physical properties of the mixed micellar system (solution turbidity and viscosity ranking) were used to further discriminate between formulations. The optimization showed that the dominant effect was the lecithin, which improves the solubilizing characteristics of the formulation with increasing concentration. The effect of salt concentration is less marked though slightly quadratic in nature. The overall increase in solubility demonstrated was from <1 microg/mL in water to 205 microg/mL in the optimized mixed micellar system.