Added value of whole-genome sequencing for management of highly drug-resistant TB.

OBJECTIVES: Phenotypic drug susceptibility testing (DST) for Mycobacterium tuberculosis takes several weeks to complete and second-line DST is often poorly reproducible, potentially leading to compromised clinical decisions. Following a fatal case of XDR TB, we investigated the potential benefit of using whole-genome sequencing to generate an in silico drug susceptibility profile. METHODS: The clinical course of the patient was reviewed, assessing the times at which phenotypic DST data became available and changes made to the therapeutic regimen. Whole-genome sequencing was performed on the earliest available isolate and variants associated with drug resistance were identified. RESULTS: The final DST report, including second-line drugs, was issued 10 weeks after patient presentation and 8 weeks after initial growth of M. tuberculosis. In the interim, the patient may have received a compromised regimen that had the potential to select for further drug resistance. The in silico susceptibility profile, extrapolated from evolving evidence in the literature, provided comparable or superior data to the DST results for second-line drugs and could be generated in a much shorter timeframe. CONCLUSIONS: We propose routine whole-genome sequencing of all MDR M. tuberculosis isolates in adequately resourced settings. This will improve individual patient care, monitor for transmission events and advance our understanding of resistance-associated mutations.

Trends and costs of high concentration fluoride toothpaste prescribing in Scotland.

Within Scotland there has been a significant increase in the prescription of 2,800 ppm and 5,000 ppm fluoride toothpaste. The objective of this paper was to analyse the trends in high concentration fluoride toothpaste (HCFT) in the five Scottish South East and Tayside (SEAT) health boards and consider the options for future national management of this prescribing. A retrospective analysis of routine prescribing data for the years 2006-2012 was carried out in primary care dental practices in Scotland. The cost of HCFT prescribing in the five Scottish health boards has increased from £15,243 (4,147 items) in 2006/07 to £206,529 (24,113 items), in 2011/12. Out of 2,430 dental list numbers, 100 list numbers (4.1%) accounted for 70% of the total prescribing costs (£144,367). The public dental service employs 153 (6%) of dentists working in Scotland, who in turn prescribe 11.6% HCFT. There is a need to ensure that the prescription of HCFT is both encouraged as best practice care but also managed appropriately to ensure that its delivery is targeted at those who are most in need.

Taking a bite out of Scotland's dental carbon emissions in the transition to a low carbon future.

BACKGROUND: Climate change is a significant global health threat requiring concerted action to reduce greenhouse gas emissions. This study provides the first systematic attempt to quantify the carbon emissions of a national dental service. METHODS: Carbon accounting combined a top-down approach using input-output analysis for indirect emissions (procurement) and a process analysis (bottom-up) approach for direct emissions (building energy, travel, waste and water). Energy and water consumption were based on meter readings, waste-related emissions from collection contracts and travel from staff and patient questionnaires. Dental companies were approached for carbon footprint data on their products. RESULTS: The carbon footprint for the service was 1798.9 tonnes CO(2)eq per annum. Travel was the greatest source (45.1%) followed by procurement (35.9%) and building energy (18.3%). Perhaps counter-intuitively older clinics had lower footprints than newer clinics as they are less energy intensive. Extrapolating the data suggests that Scotland's NHS dental service annually generates 0.16 mega tonne (Mt)CO(2)eq (4%) of the total Scottish NHS carbon footprint. CONCLUSIONS: The lack of comprehensive data reduces the ability to effectively manage emissions. Consideration needs to be given to the impact of patient travel, staff travel and new clinic construction on the carbon footprint. Medical suppliers are encouraged to provide life cycle analysis (LCA) for dental products.

Salivary duct carcinoma secreting prostate-specific antigen.

Prostate-specific antigen (PSA) is a 30 kDa glycoprotein serine protease that shows high tissue specificity for prostatic tissue, both benign and malignant. However, recent reports have shown that a variety of normal and neoplastic tissue types express PSA immunohistochemically. In addition, rare instances of the secretion of PSA by nonprostatic cancers have been reported in the literature. The authors present a case of salivary duct carcinoma associated with elevated serum levels of PSA. Both the primary tumor and metastases stained positively with anti-PSA monoclonal antibodies, but were negative with antibodies directed against prostate-specific acid phosphatase. Elevated serum PSA levels were confirmed with three different immunoassay methods. A peak serum level of 140 micrograms/L was measured and this correlates with levels of PSA associated with metastatic prostatic carcinoma. High performance liquid chromatography with a molecular sieve column characterized the serum PSA into both free protein (approximately 20%) and protein bound to alpha-1-antichymotrypsin (PSA-ACT)(approximately 80%). Molecular weights of the free PSA and PSA-ACT subfractions were 27-31 kDa and 100-110 kDa, respectively.

Estimation of pesticide exposure to greenhouse applicators using video imaging and other assessment techniques.

Pesticide exposure in greenhouse applicators was measured using the video imaging technique to assess exposure (VITAE) along with dermal patches, air monitoring, and biological assessment techniques. The exposure of five males to pesticides during high- and low-volume application methods in commercial greenhouse operations was evaluated. Failure to use precautionary handling methods when using low-volume applications resulted in the highest level of dermal tracer deposition. Results demonstrated nonuniform deposition of tracer/pesticide mixtures on various body regions, supporting earlier work that questioned the assumption of uniform deposition when assessing exposure with the dermal patch technique. By combining the tracer with an oil-based concentrate, it remained uniformly suspended in the spray solution, and deposition ratios remained constant. Estimates of pirimicarb exposure using the VITAE method were highly correlated with excretion of urinary metabolites (r2 = 0.93). The immediate visual results provided by the VITAE system to applicators proved to be a powerful educational tool in helping them adopt precautionary application techniques. The need to employ protective operating procedures when handling pesticides was demonstrated, no matter how brief the exposure period.

Estimating pirimicarb exposure to greenhouse workers using video imaging.

Exposure of greenhouse chrysanthemum workers to the pesticide pirimicarb was measured by the Video Imaging Technique to Assess Exposure (VITAE) along with air monitoring and biological assessment techniques. Workers at five commercial chrysanthemum operations were video imaged prior to debudding plants which had been treated with a fluorescent tracer and the pesticide, pirimicarb, 36-48 h earlier. After 1-4 h of debudding, workers were again imaged and the rates of tracer deposition determined with the VITAE system. Tracer deposition from contact with treated foliage was found to increase in a linear fashion over 4 h. Greatest deposition occurred on the hands and arms and represented 42% and 20% of total exposure, respectively. No detectable air residue samples of pirimicarb were found while workers were debudding plants. Monitoring of four workers for pirimicarb and its urinary metabolites revealed no detectable residues following 4 h of contact with foliage, which had been treated 48 h earlier.

A new procedure for calibrating the video imaging technique for assessing dermal exposure to pesticides.

Improvements in the calibration techniques used in a Video Imaging Technique for Assessing Exposure (VITAE) were examined. A series of standard curves measuring change in fluorescence with increased tracer deposition within narrow pre-exposure skin tone groupings on volunteer human subjects were developed. Nine highly linear curves were generated. Data from these curves were used to develop calibration curves which permitted the computerized correction of fluorescence based on the pre-exposure skin fluorescence. VITAE estimates of dermal tracer deposition were highly correlated with application rates (r2 = 0.98). The fluorescent tracer 4-methyl-7-diethylaminocoumarin was found to be stable for up to 48 h in a greenhouse environment when applied to chrysanthemum foliage or alpha-cellulose patches. The percentage of tracer which could be dislodged from chrysanthemum foliage was constant over 48 h. Improvements in the VITAE calibration techniques increase its value in providing full-body dosimetric estimates of dermal exposure to pesticides in enclosed environments.

Relative operating characteristic analysis and group modeling for tumor markers: comparison of CA 15.3, carcinoembryonic antigen, and mucin-like carcinoma-associated antigen in breast carcinoma.

Relative operating characteristic (ROC) analysis was used to examine the clinical applicability of 3 breast carcinoma tumor markers, CA 15.3, carcinoembryonic antigen, and mucin-like carcinoma-associated antigen. Each tumor marker was quantitated in single serum samples collected from 100 normal blood donors, 60 patients with nonmalignant diseases, 33 women at high risk for breast carcinoma, 30 patients with malignancies other than breast carcinoma, and 158 breast carcinoma patients including 67 with no evidence of disease following surgery, 46 with a tumor burden less than 5 g, and 45 with a tumor burden greater than 5 g. These were used to construct models for early diagnosis among those at high risk for breast carcinoma, the influence of nonmalignant disease on early diagnosis, discrimination of breast carcinoma from other adenocarcinomas, detection of early recurrence, and assessment of change in tumor burden. For each model ROC data permitted the unbiased selection of the most appropriate critical values based on the interaction of sensitivity and specificity. ROC analysis indicated that in practice the assays were remarkably similar. While CA 15.3 generally performed best, there was significant variation among models. Optimal marker selection can thus depend on specific clinical application. In some cases ROC identified a combination of markers as superior to any single assay, but this was not statistically significant.