Diphtheria in the United Kingdom, 1986-2008: the increasing role of Corynebacterium ulcerans.

Diphtheria is an uncommon disease in the UK due to an effective immunization programme; consequently when cases do arise, there can be delays in diagnosis and case-fatality rates remain high. We reviewed 102 patients with infections caused by toxigenic corynebacteria (an average of four per year) reported in the UK between 1986 and 2008: 42 Corynebacterium diphtheriae, 59 C. ulcerans and one C. pseudotuberculosis, as well as 23 asymptomatic carriers. Five fatalities were reported, all in unvaccinated patients. The major risk factor for C. diphtheriae infection continued to be travel to an endemic country. C. ulcerans infections became more common than C. diphtheriae infections in the UK; they were associated with contact with companion animals. The occurrence of indigenous severe C. ulcerans infections and imported C. diphtheriae cases highlights the need to maintain UK routine vaccination coverage at the 95% level in the UK, as recommended by the World Health Organization.

Irreversible CYP3A inhibition accompanied by plasma protein-binding displacement: a comparative analysis in subjects with normal and impaired liver function.

In this study, quinine was used as a probe substrate and erythromycin as a prototypical irreversible inhibitor of CYP3A to ascertain whether, like reversible CYP inhibition, the magnitude of irreversible inhibition is also strictly dependent on the status of liver function. The effect of erythromycin on oral quinine disposition was studied in 10 healthy subjects and in 20 patients with cirrhosis of the liver who had varying degrees of liver dysfunction. This effect was shown to be the result of two types of interaction: (i) irreversible inhibition of CYP3A-mediated quinine metabolism, the extent of which proved to be independent of liver function, and (ii) displacement of quinine from plasma protein-binding sites, the magnitude of the displacement increasing dramatically as liver function worsened. Such an interaction causes limited increases in the total concentration of the displaced drug but disproportionate increases in its free concentration; the latter increases are magnified by liver dysfunction, thereby requiring that the monitoring of free drug concentrations be made mandatory.

Instrumentation and patient characteristics that influence postoperative haemorrhage rates following tonsil and adenoid surgery.

OBJECTIVES: To investigate the effect of the type instrumentation used and the age and gender characteristics of patients on postoperative haemorrhage rates following tonsil and adenoid surgery. DESIGN: A retrospective analysis of 13 593 procedures was performed from The Patient Episode Database for Wales between 1 January 1999 and 31 March 2004. SETTING: National health policy changes created four periods of different instrument usage (reusable, single-use with diathermy, single-use alone, specified single-use with diathermy). These and the age and gender distribution of the patients were examined against four categories of postoperative haemorrhage. MAIN OUTCOME MEASURES: Postoperative haemorrhage rates were expressed as the number of complications per operations performed. Primary postoperative haemorrhage that occurred during the initial admission either required a return to theatre [R1] or was managed conservatively [N1]; secondary postoperative haemorrhage that required a return to hospital either returned to theatre [R2] or was managed conservatively [N2], were compared. RESULTS: Primary haemorrhage with return to theatre doubled, from the baseline rate with reusable instruments, from 0.6% (CI 0.5-0.8) to 1.2% (CI 0.7-1.9) when single-use instruments were introduced and remained high at 1.4% (CI 0.9-2.1) after the withdrawal of single-use diathermy. This haemorrhage rate returned to the baseline rate (0.6% CI 0.3-1.0) when specified single-use instruments were introduced. None of the other haemorrhage rates changed significantly throughout the four observation periods. Adenotonsillectomy and tonsillectomy patients have different age and gender patterns. In a univariate analysis, males over the age of 12 years were twice as likely to have haemorrhage with return to theatre than girls of the same age, 3.8% (CI 3.0-4.7) versus 1.7% (CI 1.4-2.1). CONCLUSIONS: A significant rise in serious postoperative primary haemorrhage but not secondary haemorrhage was seen following the initial introduction of single-use instruments that reverted to baseline with the introduction of specified single-use instruments. Diathermy does not appear to have affected the haemorrhage rates. There is a distinct age and gender pattern for tonsil and adenoid surgery and risk of postoperative haemorrhage. The use of arbitrary divisions of age may be misleading in studies that examine post-tonsillectomy haemorrhage.

A laboratory and clinical evaluation of single-use instruments for tonsil and adenoid surgery.

OBJECTIVES: To compare the quality and consistency of single-use adenotonsillectomy instruments available in the UK with reusable instruments and examine their performance in a clinical setting. DESIGN: A laboratory assessment of each reusable instrument created a detailed specification for the respective single-use equivalent. A surveillance system monitored the performance of a selected set of specified single-use instruments. SETTING: Single-use instruments were withdrawn shortly after their introduction in 2001. Persisting concerns from the Spongiform Encephalopathy Advisory Committee led to an investigation into the feasibility of continuing to use such instruments. MAIN OUTCOME MEASURES: The numbers of instruments from each set judged as unacceptable or as good as the original. The number and cause of instrument failure during clinical surveillance. RESULTS: Between 40% and 93% of the instruments on each set were as good as the original and between 0% and 40% of the instruments were unacceptable from six sets of steel and one set of polymer instruments. 4151 procedures were monitored between 1 February 2003 and 31 March 2004 using a total of 41 376 instruments. Problems were reported with 335 (0.8%) instruments, 46% attributable to instrument design, 14% to poor design control and 13% to instruments escaping quality control systems. Following correction of the faults, between 1 January 2004 and 31 March 2004 the problem rate fell to 0.4%. CONCLUSIONS: High quality single-use instruments for tonsil and adenoid surgery are available in the UK. Some companies offered inferior instruments not fit for their purpose. The procurement, introduction and subsequent clinical approval of single-use instruments requires a radically different approach to that currently applied to the purchase of reusable surgical equipment. Careful monitoring of their introduction is essential.

Determination of nitrates by a novel ion chromatographic method: occurrence in leafy vegetables (organic and conventional) and exposure assessment for Italian consumers.

A novel ion chromatographic method to detect nitrates in vegetables was developed, and the nitrate contents in green salad (a mixture of endive and prickly lettuce), lettuce, chicory, rocket and spinach were determined from Italian markets in 1996-2002. These leaf vegetables were included because they are currently supposed to provide most of the nitrate intake in the typical Italian diet. The highest content of nitrate was detected in chicory (6250 mg kg(-1)) and rocket (6120 mg kg(-1)), which are consumed in large quantities in some regions of Italy. Green salad and lettuce contained less nitrate (highest values = 4200 and 3300 mg kg(-1), respectively), but because they are consumed more generally, they provided 60% of the total intake of nitrates. Only a few samples were above the legal limits, with seasonal variation. A significantly higher nitrate content was found in organically grown green salad and rocket than in those conventionally produced. These data indicate that the average intake of nitrates from leafy vegetables is below the acceptable daily intake, i.e. 3.7 mg nitrate ion kg(-1) body weight day(-1), but the total intake should be monitored to protect groups at risk, such as children and vegetarians.

Community perceptions of a mass administration of an antimalarial drug combination in The Gambia.

To test the hypothesis that widespread treatment with artemisinin derivatives can reduce malaria transmission, a mass drug administration (MDA) campaign was undertaken in an area of The Gambia in 1999. Coverage of 85% of the target population was achieved, but the intervention did not reduce overall malaria transmission. We studied the perceptions, knowledge and attitudes of the community to the MDA campaign. A validated questionnaire was administered to randomly selected MDA participants (n = 90) and MDA refusers (n = 71). Individuals who believed in the importance of the MDA (adjusted OR 58.3%; 95% CI 17.4-195.8) and those who were aware that a high level of participation was needed for the MDA to be successful (adjusted OR 28.1; 95% CI 10.3-75.9) were more likely to participate. Understanding that the purpose of the MDA was to reduce malaria (adjusted OR 13.9; 95% CI 5.5-35.1) and knowledge of the fact that malaria is transmitted by mosquitoes and of the clinical signs of malaria (adjusted OR 3.4; 95% CI 3.1-9.0) were associated with participation. Individuals who discussed the MDA with other villagers (adjusted OR 5.5; 95% CI 2.2-13.5) and those who attended the sensitization meeting (adjusted OR 2.6; 95% CI 1.1-6.0) were also more likely to participate. Women were significantly more likely to participate in the MDA than men (adjusted OR 3.1; 95% CI 1.5-6.2). Individuals who refused to participate were unlikely to plan participation in future MDAs. One of the most difficult challenges in the implementation of a malaria control strategy such as an MDA is to convince villagers to participate and to make them aware that a high level of participation by the community is needed for success. We found that our sensitization meetings could be improved by giving more information on how the MDA works and finding means to generate small group discussions after the meeting.