Influence of environmental factors on disease activity in spondyloarthritis: a prospective cohort study.

OBJECTIVE: Spondyloarthritis (SpA) is a complex inflammatory disorder. We investigated the influence of environmental factors on SpA disease activity. METHODS: A prospective cohort of adults with SpA was followed for 3 years. Patients logged on to a secured Website every 3 months to complete a questionnaire. They reported whether they had been exposed to environmental factors such as stressful or traumatic life events, infections, or vaccinations. Outcome variables included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and pain and patient global assessment (PGA) on visual numerical scales (each rated 0-10). Analyses were performed using a generalized estimating equation for repeated measures, adjusted for the outcome variable collected by the previous questionnaire. RESULTS: In total, 272 patients were included in the analysis, completing the questionnaire on 2240 occasions. The average time (mean ± SD) between 2 connections to the Website was 4.0 ± 2.0 months. Occurrence of life events was followed by an increase of 0.5 (95% CI 0.4-0.7) in the BASDAI, 0.5 (95% CI 0.3-0.6) in the BASFI, 0.7 (95% CI 0.5-0.9) in the PGA, and 0.8 (95% CI 0.6-1.0) for pain (p < 0.0001 for all variations). A moderately statistically significant link was found between vaccination and an elevation of the BASDAI of 0.3 (95% CI 0.0-0.5; p = 0.032). No influence of other factors was detected. CONCLUSION: This prospective study in a dedicated SpA cohort shows for the first time a link between stressful events and disease activity. Although this link was statistically highly significant, its clinical meaning remains to be determined because the average magnitude of variation of the different variables studied was rather mild.

Reference percentiles for FEV(1) and BMI in European children and adults with cystic fibrosis.

BACKGROUND: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV(1) and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV(1) and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. METHODS: 34859 FEV(1) and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV(1) and with the WHO 2007 normative values for BMI. RESULTS: FEV(1) and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV(1) were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). CONCLUSION: The CF specific percentile approach applied to FEV(1) and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

A national internet-linked based database for pediatric interstitial lung diseases: the French network.

BACKGROUND: Interstitial lung diseases (ILDs) in children represent a heterogeneous group of rare respiratory disorders that affect the lung parenchyma. After the launch of the French Reference Centre for Rare Lung Diseases (RespiRare®), we created a national network and a web-linked database to collect data on pediatric ILD. METHODS: Since 2008, the database has been set up in all RespiRare® centres. After patient's parents' oral consent is obtained, physicians enter the data of children with ILD: identity, social data and environmental data; specific aetiological diagnosis of the ILD if known, genetics, patient visits to the centre, and all medical examinations and tests done for the diagnosis and/or during follow up. Each participating centre has a free access to his own patients' data only, and cross-centre studies require mutual agreement. Physicians may use the system as a daily aid for patient care through a web-linked medical file, backed on this database. RESULTS: Data was collected for 205 cases of ILD. The M/F sex ratio was 0.9. Median age at diagnosis was 1.5 years old [0-16.9]. A specific aetiology was identified in 149 (72.7%) patients while 56 (27.3%) cases remain undiagnosed. Surfactant deficiencies and alveolar proteinosis, haemosiderosis, and sarcoidosis represent almost half of the diagnoses. Median length of follow-up is 2.9 years [0-17.2]. CONCLUSIONS: We introduce here the French network and the largest national database in pediatric ILDs. The diagnosis spectrum and the estimated incidence are consistent with other European databases. An important challenge will be to reduce the proportion of unclassified ILDs by a standardized diagnosis work-up. This database is a great opportunity to improve patient care and disease pathogenesis knowledge. A European network including physicians and European foundations is now emerging with the initial aim of devising a simplified European database/register as a first step to larger European studies.

A French network of bipolar expert centres: a model to close the gap between evidence-based medicine and routine practice.

BACKGROUND: Bipolar disorders are a major public health concern. Efforts to provide optimal care by general practitioners and psychiatrists are undermined by the complexity of the disorder and difficulties in applying clinical practice guidelines and new research findings to the spectrum of cases seen in day to day practice. METHOD: A national network of bipolar expert centres was established. Each centre has established strong links to local health services and provides support to clinicians in delivering personalized care plans derived from systematic case assessments undertaken at the centre. RESULTS: A common set of diagnostic and clinical assessment tools has been adopted at eight centres. Evaluations are undertaken by trained assessors and cross-centre reliability is monitored. A web application, e-bipolar© is used to record data in a common computerized medical file. Anonymized data is entered into a shared national database for use in multi-centre audit and research. CONCLUSIONS: Instead of offering treatment advice based on clinical practice guidelines recommendations for selected sub-populations of patients (a 'top-down' approach), the French bipolar network offers systematic, comprehensive, longitudinal, and multi-dimensional assessments of cases representative of general bipolar populations. This 'bottom-up' strategy may offer a more efficient and effective way to transfer knowledge and share expertise as the referrer can appreciate the rationale underpinning suggested treatment protocols and more readily apply such principles and approaches to other cases. The network also builds an infrastructure for clinical cohort and comparative-effectiveness research on more representative patient populations.

Comparison of routine and on-demand prescription of chest radiographs in mechanically ventilated adults: a multicentre, cluster-randomised, two-period crossover study.

BACKGROUND: Present guidelines recommend routine daily chest radiographs for mechanically ventilated patients in intensive care units. However, some units use an on-demand strategy, in which chest radiographs are done only if warranted by the patient's clinical status. By comparison between routine and on-demand strategies, we aimed to establish which strategy was more efficient and effective for optimum patient care. METHODS: In a cluster-randomised, open-label crossover study, we randomly assigned 21 intensive care units at 18 hospitals in France to use a routine or an on-demand strategy for prescription of chest radiographs during the first of two treatment periods. Units used the alternative strategy in the second period. Each treatment period lasted for the time taken for enrolment and study of 20 consecutive patients per intensive care unit; patients were monitored until discharge from the unit or for up to 30 days' mechanical ventilation, whichever was first. Units enrolled 967 patients, but 118 were excluded because they had been receiving mechanical ventilation for less than 2 days. The primary outcome measure was the mean number of chest radiographs per patient-day of mechanical ventilation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893672. FINDINGS: 11 intensive care units were randomly allocated to use a routine strategy to order chest radiographs in the first treatment period, and 10 units to use an on-demand strategy. Overall, 424 patients had 4607 routine chest radiographs (mean per patient-day of mechanical ventilation 1.09, 95% CI 1.05-1.14), and 425 had 3148 on-demand chest radiographs (mean 0.75, 0.67-0.83), which corresponded to a reduction of 32% (95% CI 25-38) with the on-demand strategy (p<0.0001). INTERPRETATION: Our results strongly support adoption of an on-demand strategy in preference to a routine strategy to decrease use of chest radiographs in mechanically ventilated patients without a reduction in patients' quality of care or safety. FUNDING: Assistance Publique-Hôpitaux de Paris (Direction Régionale de la Recherche Clinique Ile de France).

A web-based Delphi study on the indications of chest radiographs for patients in ICUs.

BACKGROUND: Strategies for ordering bedside chest radiographs (CXRs) have substantial logistic and financial consequences in the ICU. Many of the indications for CXRs in the ICU are controversial, such as the ordering of daily routine CXRs for intubated patients. The opinions of intensivists about ordering CXRs have not been reported. Comparing these opinions to established guidelines and identifying situations where opinions diverge in the absence of guidelines are of considerable interest. METHODS: We asked 190 intensivists from 34 ICUs in the area of Paris, France, to anonymously complete a 29-item questionnaire about their opinions regarding the ordering of CXRs; each item described a clinical scenario. Of the 29 scenarios, 10 dealt with the placement of medical devices, 8 with the presence of medical devices, and 11 with other clinical situations. The study was based on a Delphi process deployed over the Internet through an original software application. Three Delphi rounds were run between January and March 2006, using the same questionnaire. Detailed feedback for the answers given during the previous round was supplied to each intensivist solicited for updating his answers. RESULTS: Eighty-two intensivists from 32 ICUs completed the study. A consensus emerged that routine CXRs were necessary for eight scenarios and unnecessary for two scenarios. The study also shed light on items without a consensus. In particular, 75% of intensivists (58% on the first round) did not support obtaining daily routine CXRs in intubated patients. CONCLUSION: The study underlines situations in which intensivists do not support the guidelines and outlines recommendations likely to be followed in clinical practice.

ICPCview: visualizing the International Classification of Primary Care.

This paper proposes a method to visualize the semantic content of data bases where the medical information is coded with the International Classification of Primary Care. The main idea is the identification of a pixel with a code and the conversion of all the data associated with these into an image the ICPCview. The method proceeds in two step, defining the reference frame and using this reference frame to visualize data. The reference frame is built by using a sign/diagnosis binary criterion, a seventeen category nosological criterion and an age ordinal criterion. The results are visualization of the signs and diagnosis of the ICPC according to gender, age and time period of the year. A limitation of the method lies in the fact that the result depends on the chosen reference frame. Further work has to be done with various reference frames and data. However the main point is that, when both the reference set of the image and of the mind of the user are built, the method is powerful at extracting the hidden content of a very large amount of data.

Respiratory-like rhythmic activity can be produced by an excitatory network of non-pacemaker neuron models.

It is still unclear whether the respiratory-like rhythm observed in slice preparations containing the pre-Bötzinger complex is of pacemaker or network origin. The rhythm persists in the absence of inhibition, but blocking pacemaker activity did not always result in rhythm abolition. We developed a computational model of the slice to show that respiratory-like rhythm can emerge as a network property without pacemakers or synaptic inhibition. The key currents of our model cell are the low- and high-threshold calcium currents and the calcium-dependent potassium current. Depolarization of a single unit by current steps or by raising the external potassium concentration can induce periodic bursting activity. Gaussian stimulation increased the excitability of the model without evoking oscillatory activity, as indicated by autocorrelation analysis. In response to hyperpolarizing pulses, the model produces prolonged relative refractory periods. At the network level, an increase of external potassium concentration triggers rhythmic activity that can be attributed to cellular periodic bursting, network properties, or both, depending on different parameters. Gaussian stimulation also induces rhythmic activity that depends solely on network properties. In all cases, the calcium-dependent potassium current has a central role in burst termination and interburst duration. However, when periodic inhibition is considered, the activation of this current is responsible for the characteristic amplification ramp of the emerged rhythm. Our results may explain controversial results from studies blocking pacemakers in vitro and show a shift in the role of the calcium-dependent potassium current in the presence of network inhibition.

Automatic detection of microcalcifications in mammography using a neuromimetic system based on retina.

The incidence of breast cancer in France is roughly 26,000 and the annual number of deaths is 11,000. The mammography is the choice examination for the early identification of the tumours in an asymptomatic population. This is a simple, reliable, inexpensive examination, allowing to identify a grave and frequent pathology, but that can be the object of an effective treatment if early detected. The recognition of the microcalcifications in the mammographies is the key for early detection of cancers. Automatic detection methods were already proposed, but they have a very weak specificity and a relatively low sensibility. Currently, the eye of the expert still remains the better judge. We propose a neuromimetic method to localize automatically the microcalcifications. In this method, we devise a network of formal neurones inspired from the mammal retina architecture. This model mimics one characteristic of the retina which is is a sensor that automatically adapts to the image characteristics to analyse and realize the outlines extraction and adaptative filtering of the pictures, based on its network properties. The results were tested using a public standardized data set (DDSM), which was designed to test the automatic detection methods. We show that our "retina" can extracts most of the microcalcifications that can be grouped together in clusters. While we achieve a 95% sensitivity, we must acknowledge a low specificity (22%). Current efforts will focus to enhance this latter parameter.

The retina as a neuromimetic model to extract data in noisy images : application to detection of microcalcification clusters in mammography.

The nervous system is a powerful information processing machine, especially for vision. Neuromimetic methods try to extract some of the most powerful strategies of the neural system to apply them to help to solve delicate engineering problems. We developed such a method to extract images hidden into noisy background. This method mimics one characteristic of the retina which is a sensor that automatically adapts to the image characteristics and realizes outlines extraction and adaptative filtering, based on its network properties. We applied this method to detect automatically the clusters of microcalcifications in mammographies. Results were tested using the standardized data set DDSM, designed to test the automatic detection methods. We show that our "retina" can extract most of the microcalcifications that can be grouped together into clusters.

XNBC V9: a simulation package of biological neural networks for the neurobiologist, easy to use, full featured and extensible.

XNBC is intended to simulate biological neural networks. XNBC V9 is an important evolution of the previous versions of the XNBC package, a full featured application for computer naive neuroscientists. XNBC is controlled via a user-friendly interface based on XWindow, Motif (Lesstif) and GTK and produces native colour PostScript high quality graphic outputs. XNBC is a public domain software package, distributed as an open source under the GNU GPL licence, easily installable using the classical configure/make/make install.

Activity in sparsely connected excitatory neural networks: effect of connectivity.

The Nucleus Tractus Solitarius (NTS) of the brainstem contains a neural circuit with only excitatory connections displaying a spontaneous activity involved in the control of respiration. A model of a network with random connections is presented and is used to investigate a possible mechanism of spontaneous activity generation consisting of the amplification of a low-background activity by the excitatory connections. First, the steady states of the network model and its ability to amplify the activity are studied. Then, a low-background activity is introduced, and dynamics of simulated networks are examined. Low-tonic, slow-phasic and fast-tonic activities are successively observed when the mean number K of connections per neuron increases. The transition between the two first types of activity is progressive whereas the transition from slow-phasic to fast-tonic activity is sharp. Simulation results show that activities of low frequency can be obtained with the proposed mechanism of spontaneous activity generation only if the network connectivity is low.

Single Neuron with Recurrent Excitation: Effect of the Transmission Delay.

Recurrent excitatory circuits and the positive feedback they imply are assigned important roles in a variety of tasks in living organisms. Such networks obviously do not exhibit saturated behaviour in the sense of extremely fast rates and/or insensitivity to input variations, as artificial systems with positive feedback generally do. It is therefore important to identify how neural saturation is avoided. A single neuron that excites itself directly provides the simplest anatomical circuitry where this problem can be studied. Such a system was simulated experimentally by Diez-Martínez and Segundo using the pacemaker neuron in the crayfish stretch receptor organ. They showed that the feedback transmission time, called "delay", was strongly influential, and small changes led to markedly different outcomes. As the delay was increased the discharge patterns went from pacemaker spike trains to multiplets separated by silent intervals to still longer bursts and longer silent intervals. We hypothesized that neuronal sensitivity decreased along the rapid successive firings (adaptation) and prevented saturation and therefore played an important role in the observed behaviour. This hypothesis was tested using models of increasing complexity. The simplest model was an integrate and fire neuron without adaptation to repeated stimuli, in this case the dynamics were qualitatively different from the experimental data. The other models exhibited adaptation to repeated stimuli. Two were relatively simple: an integrate and fire and a leaky integrator. The last model was more complex, it included membrane conductances. Neither of these models exhibited saturation when recurrent excitation was introduced. Their dynamics were in fact similar to those in the crayfish preparation, both exhibiting pacemaker firing for short delays, and multiplets or burst for intermediate delays. Simulations were therefore compatible with the hypothesis that neuronal adaptation is important in preventing saturation. Copyright 1996 Elsevier Science Ltd