Management and treatment outcomes of tuberculous patients, eastern Paris, France, 2004.

BACKGROUND: France was one of the few European countries without a national tuberculosis (TB) treatment outcome monitoring system until 2007. OBJECTIVE: To examine TB management and treatment outcomes in the eastern Paris region, and to identify patient- and management-dependent factors affecting treatment outcome. METHODS: This retrospective study focused on all cases of microbiologically confirmed Mycobacterium tuberculosis cases diagnosed in 2004 in the eastern Paris region, one of the areas of France with the highest frequency of TB. RESULTS: Treatment outcomes of 629 identified cases (males 69.6%, median age 37 years, socio-economically disadvantaged 44%, foreign-born 78%) were as follows: treatment success 70.1% (95%CI 66.5-73.7), treatment interruption 4.9% (95%CI 3.2-6.6), loss to follow-up 15.0% (95%CI 12.2-17.8), death 5.7% (95%CI 3.9-7.9), transfers 4.3% (95%CI 3.5-5.1). Non-completion of treatment was associated with sputum smear positivity, injection drug use, non-adherence and irregular follow-up in univariate analysis, and with irregular follow-up and non-adherence in multivariate analysis. Duration of TB treatment and follow-up medical visits were not applied as recommended in more than a third of cases. CONCLUSION: The treatment success rate observed in this study (70.1%) is below the World Health Organization target of 85%, and requires the implementation and evaluation of interventions to increase treatment success rates.

A systematic review of models for forecasting the number of emergency department visits.

The ability to predict patient visits to emergency departments (ED) is crucial for designing strategies aimed at avoiding overcrowding. A good working knowledge of the mathematical models used to predict patient volume and of their results is therefore essential. Articles retrieved by a Medline search were reviewed for studies designed to predict patient attendance at ED or walk-in clinics. Nine studies were identified. Most of the models used to predict patient volume were either linear regression models including calendar variables or time series models. These models explained 31-75% of patient-volume variability. Although the day of the week had the strongest effect, this variable explained only part of the variability. Other causes of this variability are to be defined. However, the performance of the models was good, with errors ranging from 4.2% to 14.4%. Adding meteorological data failed to improve model performance. The mathematical methods developed to predict ED visits have a low rate of error, but the prediction of daily patient visits should be used carefully and therefore does not allow day-to-day adjustments of staff. ED directors or managers should be aware of the model limitations. These models should certainly be used on a larger scale to assess future needs.

Haemodilution induced by hydroxyethyl starches 130/0.4 is similar in septic and non-septic patients.

BACKGROUND: Fluid therapy induces haemodilution related to plasma volume expansion. The aim of our study was to compare haemodilution after a single hydroxyethyl starches (HES) 130/0.4 infusion in two groups of patients, one with and one without sepsis. We hypothesized that a single HES challenge would induce similar sustained haemodilution in both groups. METHODS: In this prospective preliminary study, patients predicted to require a single further volume-expander infusion were included immediately before receiving 500 ml of 6% HES 130/0.4 over a 15-min period. No additional fluid was administered over the next 8 h. Haematocrit, and serum albumin and protein were determined immediately before HES infusion then after 1, 2, 3, 4, and 8 h. RESULTS: Twelve patients were included in each group. In both groups, all three haemodilution markers had significantly lower values after 1 h than at baseline. None of the values after 1 and 3 h differed significantly between the two groups. Neither did any of the other study variables show significant differences between the groups with and without sepsis. CONCLUSION: We found that a starch-based compound was as effective in inducing haemodilution in patients with sepsis as in controls without sepsis, suggesting that HES may remain within the intravascular space even in patients with sepsis. Haemodilution parameters such as haematocrit, serum albumin and serum protein are useful for assessing the duration of plasma volume expansion induced by fluid therapy in critically ill patients.

[The evaluation of health care outcomes and hospital performance indicators]. / De l'évaluation de la qualité des soins à la performance des soins.

INTRODUCTION: The assessment of the performance of health care establishments has undergone a considerable development over the past 15 years in the United States and to a lesser extent in other developed countries. BACKGROUND: The aim of measurement of performance indicators is to improve the quality of care (outcomes), patient information and the contractual arrangements with purchasers. However, this approach poses numerous methodological problems in the choice of performance indicators as well as the collection and interpretation of data. Specific structural patterns such as social and geographic environment, research and educational assignments, are often inadequately considered. In terms of public health the impact of the publication of these measurements has not been well studied. Based on the data in the literature this revue defines the measures of hospital performance and describes the main studies, their impacts and limitations. VIEWPOINT: It seems likely that the French public authorities will, in the short term, ask health care establishments to undertake this approach. CONCLUSIONS: Complimentary studies are needed to clarify the links between performance indicators and health care outcomes.

Vasoactive intestinal peptide receptor regulation and reversible desensitization in human colonic carcinoma cells in culture.

Vasoactive intestinal peptide (VIP) receptors are widely distributed in different tissues or carcinoma cells originating from entoderm and have been shown to regulate the growth of colonic adenocarcinoma cells through the action of cyclic AMP (cAMP). After exposure of cultured HT-29 human colonic carcinoma cells to 10(-8) M VIP, the cAMP-mediated signals in response to a new challenge with this neuropeptide were strongly attenuated as a function of time (half-life, less than 3 min) and VIP concentrations (half-maximal desensitization, 4 X 10(-9) M VIP). Desensitization is receptor mediated as indicated by: (a) the pharmacological specificity of the desensitization (VIP greater than secretin); (b) the considerable decrease of the potentiative action of VIP on forskolin-induced cAMP generation; and (c) the close temporal relationship between VIP receptor desensitization and the disappearance of the VIP binding sites from the cell surface. Desensitization is reversible upon the removal of VIP. Recovery of functional VIP receptors is insensitive to cycloheximide treatment, is critically dependent upon temperature, and in optimal conditions (37 degrees C) does not exceed 75 and 55% of the binding of 125I-VIP monoiodinated on tyrosine residue and VIP-induced cAMP production, respectively. The characteristics of the desensitization and internalization/recycling of the VIP receptors in carcinoma cells in culture are consistent with the transient action of this neurotransmitter and underline the biological significance of these processes. The study of drugs and natural agents interfering with membrane regulation of VIP receptor density and activity may be of considerable importance in intestinal cell tumor biology.

Combined ultrastructural and biochemical study of cellular processing of vasoactive intestinal peptide and its receptors in human colonic carcinoma cells in culture.

Desensitization of human carcinoma colonic cells in culture (HT-29) to vasoactive intestinal peptide (VIP) has been reported previously (C. Boissard, J. C. Marie, G. Hejblum, C. Gespach, and G. Rosselin, Cancer Res., 46: 4406-4413, 1986). In the present study, we have determined the ultrastructural localization of VIP and its receptor after exposure of HT-29 cells to VIP monoiodinated on tyrosyl residue 10 together with the molecular forms and the activity of the internalized VIP receptor. Quantitative electron microscope autoradiography showed that after binding at the cell surface, VIP is internalized in heterogeneous endosomes. Cross-linking experiments followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis were performed in different experimental conditions allowing us to selectively obtain cell surface-associated, internalized, or recycled receptors. No detectable alteration of the labeled VIP-receptor complex occurred during the internalization and recycling processes. Furthermore, a loss of the forskolin potentiation of the VIP-induced stimulation of adenylate cyclase was observed after VIP exposure. This feature was time and temperature dependent as was the VIP-induced loss of cell surface receptors, indicating that the internalized VIP receptor is dissociated from the adenylate cyclase.

Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas.

Data for patients with bone metastases (BMs) of differentiated thyroid carcinoma (DTC) were retrospectively studied to identify factors associated with survival. We especially studied the impact of therapies. Among the 1977 patients followed for DTC in our department from 1958 to 1999, 109 (77 females and 32 males; age range, 20--87 yr) presented BMS: All patients except 1 underwent total thyroidectomy, followed by radioiodine therapy (> or =3.7 gigabecquerels) in 95 cases. Survival rates at 5 and 10 yr were 41% and 15%, respectively. Univariate analyses indicated that a young age at BM discovery (P < 0.005) and the discovery of BM as a revealing symptom of DTC (P < 0.05) were features significantly associated with improved survival as well as radioiodine therapy (P < 10(-4)) and BM complete surgery (P < 0.02). Using multivariate analysis, the detection of BMs as a revealing symptom of thyroid carcinoma (P < 0.0005), the absence of metastasis appearance in other organs than bones during the follow-up (P < 0.03), the cumulative dose of radioiodine therapy (P < 0.0001), and complete BM surgery in young patients (P < 0.04) appeared as independent prognostic features associated with an improved survival.

Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules.

Although ultrasound (US)-guided fine needle aspiration biopsy (FNAB) is widely prescribed in nonpalpable thyroid nodules, the goal of this study was to define precisely the indications and limits of US-FNAB in a series of 450 nonpalpable nodules. Among 94 surgically controlled cases, 20 (8 infracentimetric and 12 centimetric or supracentimetric) carcinomas were diagnosed. The diagnosis of malignancy was successfully made by US-FNAB in 16 of 20 carcinomas, 3 were missed because of insufficient cytological material, and 1 was misdiagnosed. US-FNAB sensitivity and specificity were 94% and 63%, respectively. A logistic model indicated that nodule size (P < 0.6) was not associated with histological diagnosis, but that solid hypoechoic features were more likely to be malignant (P < 0.0003), with US sensitivity and specificity for malignancy of 80% and 70%, respectively. Logistic regression indicated that adequate cytological material significantly increased with nodule size (P < 0.0001). This result outlined the limits of US-FNAB in small nodules. Hence, indication of US-FNAB appears judicious in centimetric or supracentimetric nodules or in solid and hypoechoic ones. Such a management would allow the discovery of 15 of 20 carcinomas and would avoid 16% of unnecessary biopsies.

Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis).

A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group (GETC: Groupe d'Etude des Tumeurs à Calcitonine) examined the histological slides and medical records of 109 proband cases of medullary thyroid carcinoma (MTC) diagnosed on clinical features. The cases belonged to the various forms of the disease (80 sporadic and 29 familial MTC). The aim of the study was to detect histological predictors for survival by comparing morphological data from patients killed by the disease versus the others. Twenty-seven histological parameters were considered, including cellular heterogeneity, shape of the cells, and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype of the disease were also studied. First, predictive parameters of interest on survival function were selected by univariate analysis (Mantel-Cox test). Then, the extracted parameters were tested in a multifactorial analysis using the Cox's forward stepping proportional hazard model. Five parameters were significantly associated with a lower survival function: presence of necrosis in the tumor (P = .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P = .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

Cycle of VIP in the human transformed colonic epithelial cells (HT-29) in culture.

The kinetics of VIP processing in different compartments (medium, plasma membrane and intracellular) by HT-29 cells was studied using direct biochemical methods and a homogeneous monoiodinated VIP. The compartmental radioactivity was characterized by HPLC fractionation and specific receptor binding. VIP once bound to the cell surface remains intact and is rapidly and maximally internalized (less than 10 min) at 37 degrees C. Then two different processes occur: (1) release of degradation products 125I and monoiodinated tyrosine in the medium; (2) VIP remains intact in the cells representing 67.2 +/- 4.7% of total radioactivity up to 90 min. The overall processing of VIP is time- and temperature-dependent and maximal internalization of VIP with minimal medium release is observed at 20 degrees C. Our results demonstrate a receptor mediated internalization of VIP and that at least two intracellular pathways may exist in the cycle of VIP. One is associated with a complete degradation of VIP detected in the extracellular medium and is optimal at 37 degrees C. The other results in the presence of intact intracellular VIP and is optimal at 20 degrees C.

The biological relevance of HPLC-purified vasoactive intestinal polypeptide monoiodinated at tyrosine 10 or tyrosine 22.

Three major forms of monoiodinated VIP (M125I-VIP) were isolated after chloramine-T iodination and HPLC purification. The iodinated tyrosine residue was located in each form of M125I-VIP using arginase C and trypsin digestion for obtaining defined fragments containing only one tyrosine residue. The HPLC isolated iodinated fragments thus obtained were used for HPLC comigration studies with iodinated synthetic C and N terminal VIP fragments and for amino acid analysis. The first two eluting peaks 1 and 2 are (M125I-Tyr10-VIP); peak 1 has an oxidized methionine; peak 3 is a (M125I-Tyr22-VIP) which also has an oxidized methionine. A reduced counterpart of peak 3 named peak 4 was isolated by further HPLC analysis. The ability of the different species of M125I-VIP to stimulate adenosine cyclic 3',5'-phosphate (cAMP) production in transformed colonic cells in culture (HT-29) was compared to that of native VIP. The mean potencies of the M125I-VIP species expressed as a percentage relative to the potency of native VIP were, peak (1): 0.98; (2): 0.84; (3): 1.38; (4): 1.48, in the range of concentrations tested (2-60 pM). The M125I-Tyr22-VIP are significantly more active than native VIP (P less than 0.01). Oxidation of methionine or iodination of tyrosine 10 does not significantly modify the biological activity of VIP. We conclude that iodination of Tyr-22 located in the apolar helical COOH-terminal of VIP increases the effectiveness of VIP interaction with its receptors. Thus the tyrosyl residue and the localized hydrophobic features of VIP are critically involved in the function of this neurotransmitter.

[Cytopuncture in tumors of the thyroid]. / La cytoponction des tumeurs de la thyroïde.

In a large review on the utility of fine needle aspiration biopsy of the thyroid in the diagnostic management of nodular thyroid disease, procedure, morphological diagnostic criteria and difficulties, complementary technics are overviewed. Relevant articles and series are reviewed to assess the results of fine needle aspiration biopsy. A question is highlighted: wether benign unoperated thyroid nodules diagnosed by fine needle aspiration biopsy are they an underestimate risk group.

Economic implications of using pegfilgrastim rather than conventional G-CSF to prevent neutropenia during small-cell lung cancer chemotherapy.

BACKGROUND: For the prevention of chemotherapy-induced febrile aplasia, a single injection of pegfilgrastim per cycle has the same efficacy as six to ten injections of conventional granulocyte colony-stimulating factor (G-CSF). However, there are few data on the economic impact of pegfilgrastim use, especially in the context of small-cell lung cancer. METHODS: This retrospective study involved 31 patients and 129 treatment cycles (32 with pegfilgrastim and 97 with granulocyte colony-stimulating factor (G-CSF)). We estimated the direct costs for preventing and managing febrile aplasia from the payer's perspective and also conducted a willingness-to-pay study with 100 healthy subjects, in order to estimate how highly a single-jab strategy was valued relative to multiple injections. RESULTS: The costs per cycle were respectively 1743 euros+/- 837 euros and 1466 euros +/- 836 euros for the pegfilgrastim and G-CSF strategies (p < 0.001). The excess cost of the pegfilgrastim strategy was partly compensated for by the perceived value of the single-jab strategy: 88% of interviewees would prefer the pegfilgrastim strategy; 16% would be willing to pay all the excess cost (277 euros) and 67% would be willing to pay half the excess cost. CONCLUSION: In this willingness-to-pay survey, the excess cost associated with pegfilgrastim relative to other G-CSF-based prophylactic strategies is partly offset by the perceived convenience of a single injection.

The rising impact of mathematical modelling in epidemiology: antibiotic resistance research as a case study.

Mathematical modelling of infectious diseases has gradually become part of public health decision-making in recent years. However, the developing status of modelling in epidemiology and its relationship with other relevant scientific approaches have never been assessed quantitatively. Herein, using antibiotic resistance as a case study, 60 published models were analysed. Their interactions with other scientific fields are reported and their citation impact evaluated, as well as temporal trends. The yearly number of antibiotic resistance modelling publications increased significantly between 1990 and 2006. This rise cannot be explained by the surge of interest in resistance phenomena alone. Moreover, modelling articles are, on average, among the most frequently cited third of articles from the journal in which they were published. The results of this analysis, which might be applicable to other emerging public health problems, demonstrate the growing interest in mathematical modelling approaches to evaluate antibiotic resistance.

The algorithm of the cockshafer walk: a movement automaton applied to the construction of the integrated optical density profile of prometaphase chromosomes.

We present an algorithm designed to obtain the optical density profile of prometaphase chromosomes. Our movement automation (the cockshafer) is able to move along the median axis of the chromosome. The criterion used to maintain the correct movement direction lies on the distances from the automaton position to the side boundaries (lengths of the cockshafer antennae). The automaton movements are regulated by rules defined in a decision repertory. This new method does not use a transformation of the image and does not require any prior knowledge of the shape of the chromosome to be sampled.

Automated interpretation of disk diffusion antibiotic susceptibility tests with the radial profile analysis algorithm.

An original algorithm referred to as the radial profile analysis algorithm was implemented on a Macintosh Quadra 700 computer to provide an automatic determination of the inhibition zone diameters of antibiotic susceptibility tests performed with the disk diffusion method. After digitization of the petri plate image, each antibiotic disk is recognized and labeled. Pixels of the local zone around each disk are then used for generating a profile pattern that is subjected to decision rules. The resulting estimate of the inhibition zone diameter is then automatically compared with conventional breakpoints for classifying the tested strain in one of the clinical categories of antibiotic susceptibility. The program is also able to request a human reading for some rare plates difficult to interpret. The algorithm accuracy was tested by comparing the results with a combination of independent human measurements performed on the tested plates. The test sample was composed of 98 strains, and 2,552 tests of 40 distinct antibiotics were subjected to the analysis. The difference between the automatic and human diameter estimates was less than 4 mm in 90% of the tests. The agreement between the automatic and human clinical categorizations amounted to 95.5%, and severe (major and very major) disagreements were found in 5.6% of the tests performed with staphylococci but only 0.3% of the tests with gram-negative rods. We conclude that the radial profile analysis algorithm is a solid backbone for an automatic system dedicated to the clinical interpretation of disk diffusion antibiotic susceptibility tests.

Ultrastructural analysis of VIP internalization in rat beta- and acinar cells in situ.

We perfused the pancreas with 125I-labeled vasoactive intestinal peptide (VIP) to follow the concomitant distribution of radioactivity in beta- and acinar cells as a function of time. This distribution was quantitated by computer-assisted analysis of high-resolution video autoradiographs. Density labeling was expressed as normalized specific activity (disintegration density per volume density). Immediately after a 4-min perfusion of 125I-VIP, labeling in beta-cells was mainly concentrated on the cell surface and peripheral tubules and vesicles. After three 30-s pulses of 125I-VIP, separated by intervals of 3.5 min of buffer perfusion, lysosome-like structures were heavily labeled. When VIP internalization was prolonged, labeling was similar to that observed with the 4-min perfusion, indicating a high VIP disposal rate in the lysosome-like structures. In acinar cells, labeling persisted on the surface and the early vacuolar system. We conclude the following: 1) an active endocytotic system, linked to the transport and sorting of a neuromediator, is present in beta-cells; and 2) the differences between the distribution of labeling in acinar and beta-cells suggest that the regulation of VIP internalization is tissue specific.

Cell cycle models and mother-daughter correlation.

Among the different experimental features that are usually used to measure the variability of cell cycle duration (Tc), the mother-daughter correlation is a special case since apparently contradictory results have been reported from different experimental systems. Indeed, positive, null and negative experimental values have been found, raising problems in cell cycle modeling in as much as one would like a general, unified view of the control of the cell cycle. Such views are provided by mathematical models. We present a method to derive the value(s) of the correlation between mother and daughter Tcs predicted from any such model, provided Tc can be analytically expressed. An exact calculation is proposed for the case when Tc can be expressed as a linear combination of the parameters involved. Otherwise, using Taylor series expansion, an approximate expression for the correlation can be derived. In both cases, the predicted values can be compared with experimental ones. The proposed method is illustrated using the Growth Controlled model of Koch (1980, Nature 286: 80) and the Continuum model of Cooper (1982, J. theor. Biol. 94: 783). Whereas Koch's model leads to inflexible negative values of the correlation between mother and daughter Tcs, our results demonstrate that differences in the mean duration of the G1 phase may account for differences in the sign of this correlation in Cooper's model. Furthermore, the proposed method can also be applied to other correlations such as the correlation between sibling cell Tcs.(ABSTRACT TRUNCATED AT 250 WORDS)