A multi-centre prospective evaluation of the Check-Direct ESBL Screen for BD MAX as a rapid molecular screening method for extended-spectrum beta-lactamase-producing Enterobacteriaceae rectal carriage.

OBJECTIVE: A multiplex extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) quantitative polymerase chain reaction (qPCR), performed directly on rectal swabs, was compared with a culture-based protocol to study the discrepancies between the two methods, and identify existing challenges to apply this assay in routine clinical practice. The secondary objective was to assess the performance of the qPCR. MATERIALS AND METHODS: In two Dutch teaching hospitals, 573 rectal swabs were collected prospectively. Culture with additional testing with the Check-MDR CT103XL (Check-Points) was compared with the Check-Direct ESBL Screen for BD MAX (Check-Points), which detects the presence of the ESBL gene families CTX-M1, CTX-M2, CTX-M9 and SHV2/5-ESBL. The culture-based protocol (with Brilliance agar) was considered as the gold standard to assess the performance of the qPCR. RESULTS: Of the 573 rectal swabs, 74 (12.9%) were culture-positive. Eighty-four (14.7%) were qPCR-positive. There were eight culture-positive/qPCR-negative discrepancies and 18 culture-negative/qPCR-positive discrepancies. Sensitivity and specificity of qPCR vs culture were 87.7% [95% confidence interval (CI) 79.7-95.7] and 96.3% (95% CI 94.6-98.0), respectively. CONCLUSION: The Check-Direct ESBL Screen for the BD MAX is an easy-to-perform, quick molecular diagnostic test with the potential to significantly speed up screening for rectal ESBL-E carriage. Discrepancies were observed between the culture-based protocol and the qPCR in 4.5% of tested samples. Existing challenges for implementing qPCR are its limited sensitivity, the need for thorough knowledge of the local ESBL-E genes, and interpretation of culture-negative but qPCR-positive samples. It is believed that the limited sensitivity of qPCR could be optimized by including blaTEM as a molecular target, and improving the limit of detection.

New screening method to detect carriage of carbapenemase-producing Enterobacteriaceae in patients within 24 hours.

Rapid identification of patients colonized with carbapenemase-producing Enterobacteriaceae (CPE) is essential to prevent introduction and the spread of CPE in the hospital. This article presents the results of a new screening method to detect patients colonized with CPE within 24h after hospital admission. From high-risk patients rectal and throat swabs were collected and incubated overnight, after which DNA was isolated and tested for the most prevalent CPE genes (KPC, NDM, OXA-48, VIM and IMP) by a ligation-mediated real-time polymerase chain reaction. In 14 months 454 patients were screened; in six patients CPE were detected (carriage rate 1.3%).

Endometrial cancer in a cohort screened for breast cancer.

In a cohort of 25,000 women aged 40-65 years at intake in a periodic screening programme for breast cancer the occurrence of endometrial cancer was studied during a follow-up period of up to 18 years. The authors examined whether they could confirm the existence of a number of relationships between this cancer and some reproductive and anthropometric factors which had been found in several case-control studies and in a few cohort studies. A comparison was made between 147 cases of endometrial cancer occurring during the period of follow-up and a random sample of 900 women taken from the cohort (334 being premenopausal and 566 postmenopausal on the day of intake). An inverse relationship between number of children and endometrial cancer risk was found in the older group; the excess risk among nulliparous women was stronger in married than in single women. Late age at menopause (after age 52) was associated with increased risk. Use of oestrogenic drugs on day of intake for alleviating perimenopausal complaints (reported in 8% of women) increased risk, especially in the younger group. Body weight was positively associated with risk (with an odds ratio of 4 in those over 80 kg) among postmenopausal women. Because there appeared to be a moderately strong risk associated with tall height, especially among postmenopausal women, Quetelet's index performed less well than body weight itself. Nevertheless, subscapular and triceps skinfold thicknesses confirmed an effect of fatness on risk. These results are discussed with reference to other epidemiological studies, in particular two cohort studies from Norway. The effect of height, convincingly shown by Tretli and Magnus in 1990, is explained in a way which does not assume causal mechanisms operating at a young age: absolute fat mass rather than relative weight is regarded as the main determinant of risk in postmenopausal women.

Evaluation of a breast cancer screening programme--the DOM project.

In several studies it has been shown that breast cancer screening by means of mammography reduces breast cancer mortality. To ensure that when organising a service screening programme the aim is reached, it is necessary to control and monitor the process. This is possible by several methods. In this study, disease-free intervals and survival rates were used as monitoring tools. The DOM project, a breast cancer screening programme for women aged 50-64 years old at intake, started at the end of 1974. All breast cancer cases diagnosed between 1973 and 1989 were followed up to 1991. It is clear that disease-free interval and survival rates are proper predictors of the effects of screening on breast cancer mortality.

Systolic blood pressure and cardiovascular mortality among 13,740 Dutch women.

Prospective data of cardiovascular mortality in relation to the systolic blood pressure of women are scarce, especially when combined with other risk factors. The association between systolic blood pressure and cardiovascular mortality was therefore studied in a 10-year follow-up of a population of 13,740 Dutch women, born between 1911 and 1925 who participated in a population-based breast cancer screening project (the DOM Project). Age-adjusted mortality rates over the 10-year follow-up period suggest a J-shaped pattern of cardiovascular mortality according to level of systolic blood pressure. Age-adjusted total cardiovascular, coronary, and cerebrovascular mortality rate ratios were significantly greater than 1.0 among women with elevated systolic blood pressure. Within categories of other risk factors (obesity index, diabetes mellitus, current smoking, and use of antihypertensive medicines) the age-adjusted cardiovascular rate ratios did not show confounding by any of these variables. A very high increase in cardiovascular mortality was observed among hypertensive diabetic women. This study shows that elevated systolic blood pressure is associated with increased rates of cardiovascular mortality for women in this age group.

Analysis of the diagnostic performance in breast cancer screening by relative operating characteristics.

In medical usage, relative operating characteristics (ROC) refer to the symptoms, signs, and laboratory values used for making a diagnosis. Diagnosis analysis by ROC measures diagnosis performance independently of the diagnostic criteria used, thus revealing the arbitrary character of diagnosis. In order to carry out ROC analysis, the diagnosis has to be graded in levels of certainty of the presence of disease (or suspicion of a lesion). When both the graded diagnosis decisions and the ultimate proof of presence or absence of disease are available, ROC analysis can easily be carried out. Analysis of 50,102 successive examinations of 19,400 women in the Utrecht breast cancer screening projects presents a remarkably good fit of the observed data with the calculated values. In the medical context even small deviations of the actual sensitivity and specificity values from the ROC curve values must be considered as signs of differences in the diagnosis procedure and should lead to further analysis of the diagnostic criteria and the examined population. Consequently the separate effect of diagnosis impairment by the mammographic risk patterns (Wolfe) on diagnostic accuracy could be isolated. The effect of age on the detection capability of breast cancer by mammography appeared to operate in narrow age groups.

Diagnosis analysis in breast cancer and cervical cancer screening.

Assessment of the accuracy of diagnostic procedures has been made independent of the diagnostic criteria used by means of Relative Operating Characteristics (ROC) analysis. A ROC curve describes the mutual relationship between the sensitivity and specificity of a diagnostic decision on the basis of various diagnostic criteria. The construction of such ROC curves is made possible if diagnoses are graded into levels of certainty. The curve enables the choice of an operating point with predetermined sensitivity and specificity values for the diagnosis decision. The population-based breast-cancer and cervical cancer screening projects carried out in Utrecht demonstrated an excellent fit between actual data and the calculated ROC curves. Analysis of the accuracy or performance of cytological diagnosis uncovered a problem arising from the similarly graded histopathological reference criteria used to determine the 'truth' of the cytological diagnosis decisions. The proposed solution is a serial calculation of ROC curves, one for each level differentiating between the histopathological categories. The ensuing three-dimensional ROC hill may reveal a summit marking numerically advantageous diagnosis criterion levels for both the test and the disease to be detected, or a depression signalling locally below-standard detection performance.