Evaluation of the performance of rapid tests for screening carriers of acquired ESBL-producing Enterobacterales and their impact on turnaround time.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales constitute a global burden for hospital infection, and the identification of carriers by screening patients at risk is recommended by several guidelines. AIM: To evaluate the impact of rapid ESBL tests on the turnaround time (TAT) of screening. METHODS: Rectal swabs were analysed by culture and synergism tests for identification of non-Esherichia coli Enterobacterales that produce ESBLs (NEcESBL-producing Enterobacterales). The Rapid ESBL NP and NG CTX-M MULTI tests were performed on colonies grown on chromogenic media. The results of polymerase chain reaction and sequencing of ESBL genes were used as the gold standard. RESULTS: Among 473 analysed swabs, 75 (15.9%) grew NEcESBL-producing Enterobacterales, leading to 89 isolates. Sensitivities of the synergism, Rapid ESBL NP and NG CTX-M MULTI tests were 0.97 [95% confidence interval (CI) 0.88-0.99], 0.81 (95% CI 0.69-0.89) and 0.90 (95% CI 0.80-0.96), respectively. Specificities were 0.92 (95% CI 0.73-0.99), 0.85 (95% CI 0.64-0.95) and 0.96 (95% CI 0.78-1.00), respectively. Considering the 473 rectal swabs, ESBL screening using the synergism, Rapid ESBL NP and NG CTX-M MULTI tests was calculated. Sensitivities were 0.96 (95% CI 0.86-0.99), 0.81 (95% CI 0.68-0.90) and 0.91 (95% CI 0.79-0.97); specificities were 1.00 (95% CI 0.98-1.00), 0.99 (95% CI 0.98-1.00) and 1.00 (95% CI 0.99-1.00); positive predictive values were 0.96 (95% CI 0.86-0.99), 0.94 (95% CI 0.81-0.98) and 1.00 (95% CI 0.91-1.00); and negative predictive values were 1.00 (95% CI 0.98-1.00), 0.98 (95% CI 0.96-0.99) and 0.99 (95% CI 0.97-1.00), respectively. When no NEcESBL-producing Enterobacterales were observed, the mean TAT was 30 h. When NEcESBL-producing Enterobacterales were identified, the mean TATs were 74.7, 38.0 and 36.7 h for the synergism, Rapid ESBL NP and NG CTX-M MULTI tests, respectively. CONCLUSION: The two rapid ESBL tests showed good performance and allowed a reduction in TAT for screening protocols to identify patients carrying ESBL-producing Enterobacterales.

The rostromedial zona incerta is involved in attentional processes while adjacent LHA responds to arousal: c-Fos and anatomical evidence.

Neurons producing melanin-concentrating hormone (MCH) are located in the tuberal lateral hypothalamus (LHA) and in the rostromedial part of the zona incerta (ZI). This distribution suggests that rostromedial ZI shares some common features with the LHA. However, its functions with regard to arousal or feeding, which are often associated with the LHA, have not been thoroughly investigated. This study analyses the responses in the tuberal LHA and adjacent rostromedial ZI after experiments related to arousal, exploration, food teasing and ingestive behavior. Specific aspects of the connections of the rostromedial ZI were also studied using retrograde and anterograde tract-tracing approaches. The rostromedial ZI is activated during exploratory and teasing experiments. It receives specific projections from the frontal eye field and the anterior pole of the superior colliculus that are involved in gaze fixation and saccadic eye movements. It also receives projections from the laterodorsal tegmental nucleus involved in attention/arousal. By contrast, the tuberal LHA is activated during wakefulness and exploratory behavior and reportedly receives projections from the medial prefrontal and insular cortex, and from several brainstem structures such as the periaqueductal gray. We conclude that the rostromedial ZI is involved in attentional processes while the adjacent tuberal LHA is involved in arousal.

Association of diagnostic work-up with subsequent attendance in a breast cancer screening program for false-positive cases.

The objective of this study is to determine whether the likelihood of returning for routine breast cancer screening differed for false-positive cases depending on the diagnostic work-up. Using the original data from a French population-based breast cancer screening program, we compared the attendance rates at the subsequent round of screening for 16,946 and 1,127 participants who received negative (i.e., American College of Radiology, ACR, categories 1-2) and false-positive mammograms, respectively. False-positive mammograms were categorized ACR 0 (i.e., warranting additional imaging evaluation), 3 (i.e., warranting clinical and imaging follow-up), and 4-5 (i.e., warranting biopsy). We estimated the odds ratios of attendance at subsequent screening round using logistic regression, adjusting for age and history of previous mammography. The attendance rates at the subsequent screening round were 80.6% for women who received negative mammograms versus 69.6, 74.3, and 70.1% for women who received false-positive mammograms warranting additional imaging evaluation, clinical and imaging follow-up, or biopsy, respectively. In comparison to women who received negative mammograms, the corresponding adjusted odds ratios of returning for routine screening were 0.6 [95% confidence interval (CI) 0.4-0.8], 0.8 (95% CI 0.6-0.9), and 0.6 (95% CI 0.4-0.8). No significant differences were found in odds ratios of attendance across ACR categories among women who received false-positive mammograms. Similar figures were observed for attending at least one of the two subsequent screening rounds. In conclusion, in comparison to women with normal or benign findings on index mammograms, false-positive cases warranting additional imaging evaluation, clinical and imaging follow-up, or biopsy had uniformly decreased odds of attending subsequent routine screening rounds.

Breast cancer incidence and time trend in France from 1990 to 2007: a population-based study from two French cancer registries.

BACKGROUND: The hypothesis of a link between breast cancer and hormone replacement therapy (HRT) is evoked to explain the recent decrease of incidence observed in several countries. The purpose of our study is to analyse the evolution of breast cancer incidence by stage. MATERIALS AND METHODS: We used data from Tarn and Isère French cancer registries for the period 1990-2007. Trends of annual world population standardised incidence rates were studied using the Joinpoint method. RESULTS: From 1990 to 1999, the incidence of invasive breast cancer increased annually by 1.2%, then by 4.8% from 1999 till 2003 and then decreased by 1.7%. For the women aged 50-74 years, annual changes were, respectively, 1.5%, 6.0% and 3.4%. In this group, the incidence of T1/T2-N0-M0 stages increased annually by 4.6% until 2003 and then decreased by 2.2%. Since 1990, the incidence of in situ breast cancer increased annually by 5%. From 2003 to 2004, prescribing of HRT decreased substantially. CONCLUSIONS: : Since 2003, the incidence of invasive breast cancer decreased for women aged 50-74 years, mainly involving T1/T2-N0-M0 stages. The reduction in HRT prescription may partly explain this decrease. The incidence of in situ breast cancer didn't decrease during the whole period.

Colonoscopy practices, and colorectal cancer and polyp screening, as assessed in the French district of Isère from May to July in 2004.

BACKGROUND: A pilot program of organized screening for colorectal cancers was conducted in Isère, an administrative district in France. A fecal occult blood test (Hemoccult II(®)) was proposed for all individuals aged greater than 50 years (women since 1991 and men since 2002), followed by colonoscopy for those testing positive. A prospective study was carried out from May to July in 2004 and compared with a similar study conducted in 1996. The goal was to investigate colonoscopy practices, especially the role of screening. METHODS: Gastroenterologists practising in Isère (n=39/42 practitioners) completed a questionnaire including their patients' age and gender, indications, methods and results for all colonoscopies performed in those aged greater than 20 years. Any tissue samples taken were sent away for histological evaluation. RESULTS: The study involved 2558 colonoscopies (54% female, 73% patients aged greater or equal to 50 years), an increase of 35% from 1996 to 2004. Of the patients referred, 50.0% were symptomatic (pain; bowel problems: 28.7%; rectal bleeding: 21.3%), 23.5% had colonic disease and 22.5% came from screening (3.1% had positive stool tests, 17.8% had a family history). Recommendations related to family history (update of the 1998 consensus conference: screening indicated for patients with a first-degree relative diagnosed with cancer or advanced polyps aged less than 60 years) were well applied in terms of relatedness (81%) but, in 52% of cases, the age was greater than 60 years. Colonoscopy was carried out in almost all cases (0.1% failure), with complications in 0.4% of the examinations. Of the 2558 colonoscopies performed, 10% revealed advanced polyps or cancer: 30% were following a positive test compared with 8% for symptoms and 6% with a family history. Multivariate analyses showed that polyps greater or equal to 10mm or malignant tumors are 1.5 times more common in men than in women, and six times more frequently seen in patients having colonoscopy following a positive test for blood in stools than in those with a family history of colorectal cancer. The number of pathologies found increased significantly in those aged greater than 50 years. CONCLUSION: This cross-sectional survey of colonoscopy practices in Isère shows an increase in the number of colonoscopies performed between 1996 and 2004. This increase is not explained by expansion of the screening program, which was the reason for only 3% of colonoscopies. However, the best diagnostic yield for advanced polyps or cancers was obtained in screened patients (30%).

[Evaluation of the follow-up of women aged 50-74 years after cervical cytological Ascus abnormalities in cancer screening: adherence to clinical practice guidelines in Isere, France; 1991-2000]. / Evaluation de la prise en charge des femmes de 50 à 74 ans après frottis du col de l'utérus répondu Ascus dans un dépistage organisé en Isère 1991-2000 : application de la conduite à tenir de l'Agence nationale d'accréditation et d'évaluation en santé.

OBJECTIVES: The aim of this study is to compare to the guideline (1998 and 2001) the follow-up of Ascus cytological abnormalities among women aged 50-74 years who have participated at the combined breast, cervical and colorectal cancer screening programme from 1991 to 2000 in Isère, France. PATIENTS AND METHODS: The follow-up of 1154 women with Ascus smear was analysed. A woman was defined according follow-up if she have made a colposcopy or biopsy less than four months after one positive smear or if she has repeated three smears: 3-7 months and 10-14 months after the positive smear and 1 year after the last negative smear. RESULTS: The follow-up was according to guidelines for 28.4% of the 1154 women (150 women are unknowns), 58.6% had a follow-up with too long delay and 17.2% had an uncompleted follow-up. The follow-up did not differ before 1998. It did not differ from women age. Women who were treated by gynaecologist (548) had a better follow-up (according: 35.4%) than the women who were treated by a general practitioner (595). DISCUSSION AND CONCLUSION: The follow-up of Ascus cytological abnormalities is not according to guideline. The follow-up in the screening program will be intensified.

[Sensitivity and specificity of the breast screening program in the Isere region based on positive results between 1991 and 1999]. / Analyse de la sensibilité et de la spécificité des mammographies en fonction des taux de tests positifs dans le programme de dépistage organisé de l'Isère de 1991 à 1999.

PURPOSE: The screening program guidelines specify that the call back rate of women for additional imaging (positive mammogram) should not exceed 7% at initial screening, and 5% at subsequent screening. Materials and methods. Results in the Isere region (12%) have prompted a review of the correlation between the call back rate and indicators of quality (detection rate, sensitivity, specificity, positive predictive value) for the radiologists providing interpretations during that time period. RESULTS: Three groups of radiologists were identified: the group with call back rate of 10% achieved the best results (sensitivity: 92%, detection rate: 0.53%, specificity: 90%). The group with lowest call back rate (7.7%) showed insufficient sensitivity (58%). The last group with call back rate of 18.3%, showed no improvement in sensitivity (82%) and detection rate (0.53%), but showed reduced specificity (82%). CONCLUSION: The protocol update in 2001 does not resolve this problematic situation and national results continue to demonstrate a high percentage of positive screening mammograms. A significant increase in the number of positive screening examinations compared to recommended guidelines is not advantageous and leads to an overall decrease in the quality of the screening.

Analysis of the effect of age on the prognosis of breast cancer.

To explore the effect of age at diagnosis on relative survival from breast cancer at different cancer stages and grades, using appropriate statistical modeling of time-varying and non-linear effects of that prognostic covariate. Data on 4,791 female invasive breast cancers diagnosed between 1990 and 1997 were obtained from a French cancer registry. The effect of age on relative survival was studied using an approach based on excess rate modeling. Different models testing non-linear and non-proportional effects of age were explored for each grade and each stage. In the whole population, the effect of age was not linear and varied with the time elapsed since diagnosis. When analyzing the different sub-groups according to grade and stage, age did not have a significant effect on relative survival in grade 1 or stage 3 tumors. In grade 2 and stage 4 tumors, the excess mortality rate increased with age, in a linear way. In grade 3 tumors, age was a time-dependent factor: older women had higher excess rates than younger ones during the first year after diagnosis whereas the inverse phenomenon was observed 5 years after diagnosis. Our findings suggest that when taking into account grade and stage, the time-varying impact of young age at diagnosis is limited to grade 3 tumors, without evidence of worst prognosis at 5 years for the youngest women.

QSOX sulfhydryl oxidase in rat adenohypophysis: localization and regulation by estrogens.

The expression of the rat quiescin sulfhydryl oxidase (rQSOX) and its putative regulation by estrogens were investigated in the adenohypophysis. Immunohistochemical observations revealed that rQSOX protein is abundantly expressed throughout the anterior lobe of the pituitary, and can be found in almost all the different cell populations. However, as shown by double immunohisto-chemistry, the cells displaying the strongest rQSOX labeling belong to a subset of gonadotrophs. Immunoelectron microscopy showed that, in adenohypophyseal cells, the protein is linked to the membranes of the rough endoplasmic reticulum, the Golgi apparatus and to dense-core secretory granules. These results are consistent with the secretion of the protein and its presumed role in the extracellular matrix. According to its sulfhydryl oxidase function, rQSOX could also participate in the intracellular folding of secreted proteins or hormones like LH and FSH and act as an endogenous redox modulator of hormonal secretion. A semiquantitative RT-PCR analysis of rQSOX level across the estrous cycle and the fact that chronic administration of 17 beta-estradiol to ovariectomized rats led to a sustained up-regulation of rQSOX in the pituitary suggest that rQSOX expression is controlled by sex hormone levels. Further investigations are needed in order to elucidate its precise roles in that gland and the mechanisms of its regulation.