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The hepatitis C virus (HCV) life cycle is closely associated with lipid metabolism. In particular, HCV assembly initiates at the surface of lipid droplets. To further understand the role of lipid droplets in HCV life cycle, we assessed the relationship between HCV and the adipose differentiation-related protein (ADRP), a lipid droplet-associated protein. Different steps of HCV life cycle were assessed in HCV-infected human Huh-7 hepatoma cells overexpressing ADRP upon transduction with a lentiviral vector. HCV infection increased ADRP mRNA and protein expression levels by 2- and 1.5-fold, respectively. The overexpression of ADRP led to an increase of (i) the surface of lipid droplets, (ii) the total cellular neutral lipid content (2.5- and 5-fold increase of triglycerides and cholesterol esters, respectively), (iii) the cellular free cholesterol level (5-fold) and (iv) the HCV particle production and infectivity (by 2- and 3.5-fold, respectively). The investigation of different steps of the HCV life cycle indicated that the ADRP overexpression, while not affecting the viral replication, promoted both virion egress and entry (~12-fold), the latter possibly via an increase of its receptor occludin. Moreover, HCV infection induces an increase of both ADRP and occludin expression. In HCV infected cells, the occludin upregulation was fully prevented by the ADRP silencing, suggesting a specific, ADRP-dependent mechanism. Finally, in HCV-infected human livers, occludin and ADRP mRNA expression levels correlated with each other. Alltogether, these findings show that HCV induces ADRP, which in turns appears to confer a favorable environment to viral spread. [ABSTRACT FROM AUTHOR]

Metabonomic studies involve the analysis of large numbers of samples to identify significant changes in the metabolic fingerprints of biological systems, possibly with sufficient statistical power for analysis. While procedures related to sample preparation and spectral data acquisition generally include the use of independent sample batches, these might be sources of systematic variation whose effects should be removed to focus on phenotyping the relevant biological variability. In this work, we describe a grouped-batch profile (GBP) calibration strategy to adjust nuclear magnetic resonance (NMR) metabolomic data-sets for batch effects either introduced during NMR experiments or samples work-up. We show how this method can be applied to data calibration in the context of a large-scale NMR epidemiological study where quality control samples are available. We also illustrate the efficiency of a batch profile correction for NMR metabonomic investigation of cell extracts, where GBP can significantly improve the predictive power of multivariate statistical models for discriminant analysis of the cell infection status. The method is applicable to a broad range of NMR metabolomic/metabonomic cohort studies. [ABSTRACT FROM AUTHOR]

Background and Objective: The efficacy and safety of empagliflozin in the treatment of chronic kidney disease (CKD) were demonstrated in the EMPA-KIDNEY trial, which showed a 28% reduction in combined risks of kidney disease or death from cardiovascular causes (hazard ratio, 0.72; 95% confidence interval, 0.64-0.82; p < 0.001) compared with placebo. Based on these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of CKD in France., Methods: A Markov state microsimulation model was adapted to compare the health and economic outcomes in France, considering a healthcare system perspective, in patients treated with empagliflozin in addition to SoC versus patients treated with SoC alone. The model simulated the intention-to-treat population of the trial, transitioning between 18 mutually exclusive and collectively exhaustive health states defined based on the Kidney Disease: Improving Global Outcomes classification. For each arm, the model estimated (over a 25-year time horizon) the number of events and deaths, and the costs associated with these events, to calculate the incremental cost-effectiveness ratio. The resources used were derived using French authorities reports, literature, and French CKD guidelines. Both economic and health outcomes were discounted at a 2.5% annual rate according to French guidelines., Results: The model predicted that using empagliflozin + SoC to treat patients with CKD would prevent CKD-related complications and deaths associated with a cardiovascular event or all-cause deaths while in kidney replacement therapy, resulting on average in a discounted gain of 1.29 years in overall survival (9.48 years vs. 8.19 with SoC alone). Empagliflozin costs (treatment, events, and disease management) were completely offset by the cost savings from avoided kidney failure events. Overall, empagliflozin + SoC would be more effective and less costly than SoC alone and would therefore be the dominant treatment strategy. The sensitivity analyses conducted support the results' robustness in showing the dominance of empagliflozin + SoC over SoC alone., Conclusions: The base-case results indicate that empagliflozin + SoC is a dominant strategy compared with the current SoC for the management of CKD in France. Empagliflozin + SoC would have a positive impact on patients with CKD by slowing CKD progression and leading to the prevention of kidney failure events on top of all-stages CKD complications., Competing Interests: Declarations Competing Interests Harinala Groyer and Denis San were employed by Boehringer Ingelheim France at the time of manuscript submission. Romain SUPIOT, Jean TARDU, Nicolas VIRELY, and Marine SIVIGNON were employed by Putnam at the time of manuscript submission. Pierre Lévy reports serving on a consultancy or paid advisory board for Bayer, Boehringer Ingelheim, Newcard. Anastasia Ustyugova is employed by Boehringer Ingelheim International GmbH, Ingelheim, Germany. Ziad Massy reports having received grants for CKD-REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp & Dohme-Chibret, Sanofi- Genzyme, Lilly, Otsuka, AstraZeneca, Vifor, and the French government, as well as fees and grants to charities from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. The sponsors had no role in the design, execution, interpretation, or writing of the present study. Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable. Availability of Data and Material: No other data or material are available than the ones published in this article. Code Availability No code or information from the cost-effectiveness model is available. Authors' Contributions The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Harinala Groyer managed the project on the Boehringer Ingelheim side and proofread the manuscript. Romain Supiot managed the project on the Putnam side and wrote the manuscript. Jean Tardu, Nicolas Virely, Marine Sivignon, Denis San, and Anastasia Ustyugova contributed to the analysis and proofread the manuscript. Pierre Lévy was consulted as an economic expert and proofread the manuscript. Ziad Massy was consulted as a clinical expert to validate assumptions and key inputs of the model and proofread the manuscript. Funding The study was supported and funded by Boehringer Ingelheim., (© 2024. The Author(s).)

This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety disorder (GAD) in adult patients. We selected randomized controlled trials on various medications used to treat GAD in adult patients. An existing systematic literature review (Kong et al., 2020) was used to identify relevant studies published before 2020. Outcomes of remission and discontinuation due to adverse events (AEs) were analyzed, following a random-effects network meta-analysis approach. Of 25 identified studies, 20 and 22 studies were included in the network meta-analysis for studying the remission and discontinuation (due to AEs) outcomes, respectively. A statistically significant difference in the remission rate was observed between agomelatine and pregabalin [odds ratio (OR), 2.22; 95% confidence interval (CI), 1.19-4.21]. For the other comparators, the results were nonsignificant; however, all the point estimates were in favor of agomelatine. Similarly, for discontinuation because of AEs, the point estimates leaned consistently toward agomelatine suggesting its higher tolerability. The probabilities of agomelatine having the highest remission rate and lowest discontinuation (due to AEs) rate were 67% and 68%, respectively. Based on its demonstrated effectiveness and tolerability, agomelatine can be considered as a drug of choice for the treatment of GAD., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess a new polynomial regression formula integrating the refractive prediction error of the first-operated eye to improve the intraocular lens power calculation of the second eye in cataract surgery., Setting: Centre Hospitalier Universitaire, Toulouse, France., Design: Retrospective multicentric dataset study., Methods: A polynomial regression formula, WeOptimeye2nd (WO2nd), was developed using a machine-learning algorithm trained on a dataset of 534 patients who underwent sequential bilateral cataract surgery. A separate multicentric dataset was used to retrospectively calculate predicted refraction with WO2nd, SRK/T and Barrett Universal II formulas, and 3 other methods of constant factors (CFs) second-eye refinement (CF0.38, CF0.35, and CF0.5). Mean absolute errors (MAEs) and percentage of eyes within ±0.25, ±0.5, and ±1.0 diopter (D) from predicted spherical equivalent were compared between formulas., Results: The study comprised data on 722 patients. In the overall population, WO2nd had the lowest MAE: 0.339 vs 0.347 (P = .137), 0.340 (P = .956), 0.350 (P = .066), 0.399 (P < .001), and 0.410 (P < .001), with CF0.38, CF0.5, and CF0.35, Barrett II, and SRK/T, respectively. WO2nd had the highest percentage of eyes within ±0.5 D of the predicted refraction, and the difference was statistically significant vs SRK/T and Barrett II formulas but not vs CF0.38, CF0.5, and CF0.35. WO2nd performed the best in axial length (AL) < 22 mm with the lowest MAE and a statistically significant difference vs any other formula., Conclusions: WO2nd improved the refractive outcome of the second-operated eye and performed well in extreme AL and mean keratometry subgroups., (Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Objectives: To develop a new tool to assess constraints due to urinary treatments in neurological patients., Materials and Methods: A prospective, monocentric study has been conducted from January to May 2017. Out-patients (multiple sclerosis, spinal cord injury, Parkinson disease) were included in a referral center if they had LUTS treatment for at least 3 months. To validate psychometric properties, we conducted a literature review, qualitative interviews, and discussion with a panel of six experts. Comprehension, acceptation, and pertinence were tested by a pilot study. A validation study, designed to calculate content validity, internal consistency reliability, and test-retest reliability [intraclass correlation coefficient (ICC)] has been conducted. The primary outcome was good psychometric properties defined with Cronbach's α > 0.7 and ICC > 0.7., Results: Comprehension, acceptation, and pertinence were excellent. Validation study showed a perfect content validity (r2 = 1) and excellent internal consistency reliability (Cronbach' α = 0.90). Total score was between 0 (best score) to 66 (maximal constraints). Test-retest reliability calculated using ICC was 0.81. Time to fill questionnaire was 4 min 20 s. The final version was composed by 22 items., Conclusion: LUTS TCA is the first validated tool to assess constraints of urinary treatment and has excellent psychometric properties.

Chronic infection with hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma. However, the molecular mechanisms linking the infection to cancer development remain poorly understood. Here we used HCV-infected cells and liver biopsies to study how HCV modulates the glutaminolysis pathway, which is known to play an important role in cellular energetics, stress defense, and neoplastic transformation. Transcript levels of glutaminolytic factors were quantified in Huh7.5 cells or primary human hepatocytes infected with the Japanese fulminant hepatitis 1 HCV strain as well as in biopsies of chronic HCV patients. Nutrient deprivation, biochemical analysis, and metabolite quantification were performed with HCV-infected Huh7.5 cells. Furthermore, short hairpin RNA vectors and small molecule inhibitors were used to investigate the dependence of HCV replication on metabolic changes. We show that HCV modulates the transcript levels of key enzymes of glutamine metabolism in vitro and in liver biopsies of chronic HCV patients. Consistently, HCV infection increases glutamine use and dependence. We finally show that inhibiting glutamine metabolism attenuates HCV infection and the oxidative stress associated with HCV infection., Conclusion: Our data suggest that HCV establishes glutamine dependence, which is required for viral replication, and, importantly, that glutamine addiction is a hallmark of tumor cells. While HCV induces glutaminolysis to create an environment favorable for viral replication, it predisposes the cell to transformation. Glutaminolytic enzymes may be interesting therapeutic targets for prevention of hepatocarcinogenesis in chronic hepatitis C. (Hepatology 2017;65:789-803)., (© 2016 by the American Association for the Study of Liver Diseases.)

Background: Paediatric obstructive sleep apnoea syndrome (OSAS) is a highly prevalent condition carrying increased risk for impaired cognitive and cardiovascular function. The standard diagnosis consists of full-night polysomnography (PSG), but limited access to PSG leads to substantial under-diagnosis. The use of a validated and simple diagnostic screening tool to predict OSAS could prioritise night sleep recordings in children at risk of OSAS, and help in clinical decision-making., Objective: This study aimed to prospectively assess the performance of the French version of the severity hierarchy score (SHS) in paediatric OSAS. This score consists of a discriminative subset of six respiratory items, and has already been validated in English for screening OSAS in the general paediatric population., Methods: A total of 96 children (mean age 7.1 ± 2.4 years; BMI z-score: -0.03 ± 1.50) were recruited; they had been were referred to two academic sleep centres in France for the putative diagnosis of sleep-disordered breathing. The parents completed the SHS questionnaire prior to PSG. Sensitivity and specificity of the SHS for detecting moderate OSAS, defined by an apnoea-hypopnoea index (AHI) of ≥5/hours of total sleep time (TST), were assessed, and ROC analysis was performed., Results: An SHS score of >2.75 exhibited an 82% sensitivity, 81% specificity, and 92% negative predictive value for detecting an AHI of ≥5/hour TST in the cohort., Conclusion: The French version of the SHS emerged as favourably suited for the screening for OSAS in children., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: The objective of our study was to evaluate the impact of an automatic tube potential selection (ATPS) on the delivered dose and image quality in unenhanced head computed tomography (CT) scans of infants., Materials and Methods: Unenhanced head CT scans were acquired before and after the introduction of an ATPS in full automatic mode in two groups of 20 patients under one year of age. The delivered dose (CDTIvol) as the quantitative (contrast-to-noise ratio) and qualitative (based on the European CT criteria) image quality were compared on the supra- and infratentorial regions by three senior pediatric radiologists. Mann-Whitney and Fisher exact tests were performed. An interobserver Fleiss's kappa agreement was calculated for each criterion., Results: The use of an ATPS allowed a significant reduction in the delivered dose (-21%, p=0.0005) with no significant difference of the contrast-to-noise ratio in supra- (-5%, p=0.21) and infratentorial regions (+16%, p=0.96). In all cases, dose reduction was obtained with the same value of 100kV. It maintained a good qualitative image quality (e.g., differentiation between gray and white matter in supra-tentorial region: p=0.470). The interobserver Fleiss's kappa agreements were good to excellent., Conclusion: ATPS is a tool that can significantly reduce the delivered dose by choosing the most appropriate tube voltage while maintaining image quality in unenhanced head CT scans of infants., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Inflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it eliminates ROS is less well known. The role of the ROS scavenger glutathione peroxidase 4 (GPx4), induced by HCV, in the viral life cycle was analysed., Design: The study was performed using a replicative in vitro HCV infection model and liver biopsies derived from two different CHC patient cohorts., Results: A screen for HCV-induced peroxide scavengers identified GPx4 as a host factor required for HCV infection. The physiological role of GPx4 is the elimination of lipid peroxides from membranes or lipoproteins. GPx4-silencing reduced the specific infectivity of HCV by up to 10-fold. Loss of infectivity correlated with 70% reduced fusogenic activity of virions in liposome fusion assays. NS5A was identified as the protein that mediates GPx4 induction in a phosphatidylinositol-3-kinase-dependent manner. Levels of GPx4 mRNA were found increased in vitro and in CHC compared with control liver biopsies. Upon successful viral eradication, GPx4 transcript levels returned to baseline in vitro and also in the liver of patients., Conclusions: HCV induces oxidative stress but controls it tightly by inducing ROS scavengers. Among these, GPx4 plays an essential role in the HCV life cycle. Modulating oxidative stress in CHC by specifically targeting GPx4 may lower specific infectivity of virions and prevent hepatocarcinogenesis, especially in patients who remain difficult to be treated in the new era of interferon-free regimens., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To examine the frequency and determinants of underperception of naps in older adults referred for a sleep assessment., Design: Prospective study., Setting: Outpatient geriatric sleep clinic., Participants: Individuals aged 60 and older referred for insomnia complaints or suspected sleep apnea (N = 135)., Measurements: Tests included clinical interview, sleepiness scale, anxiety and depression scale, Insomnia Severity Index (ISI), Mini-Mental State Examination (MMSE), and overnight polysomnography, followed by multiple sleep latency tests. At the end of each of four nap opportunities, participants answered whether they had slept during the test. Nap underperception was defined as two or more unperceived naps., Results: Of the 105 participants who napped at least twice, 42 (40%) did not perceive at least two naps. These participants had lower MMSE scores (P = .01) and were more likely to be taking benzodiazepines (P = .008) than the 63 participants who did not underperceive their naps but had similar demographic characteristics, sleep diagnoses, depression and anxiety scores, and polysomnography measures. Both groups had similarly short mean daytime sleep latencies (9.7 ± 4.5 minutes and 9.8 ± 3.7 minutes), but participants who underperceived their naps scored lower on the Epworth Sleepiness Scale (5.6 ± 4.0, vs 9.6 ± 4.8, P < .001). An ISI of 11 or greater, a MMSE score of 26 or less, and a sleepiness score of 8 or less were each independently associated with underperception of naps. The combination of these three factors yielded a positive predictive value of 93% and a negative predictive value of 71% for nap underperception., Conclusion: Older adults referred for sleep consultation with cognitive impairment and greater insomnia symptoms frequently underperceive naps, leading them to underestimate their level of sleepiness. In such cases, objective measures of daytime sleepiness would be better than the Epworth Sleepiness Scale., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

The use of vaccines to prevent diseases in children, adults, and the elderly results in fewer medical visits, diagnostic tests, treatments, and hospitalisations, which leads to substantial savings in healthcare costs each year in Europe and elsewhere. Vaccines also contribute to reducing resource utilisation by preventing nosocomial infections, such as rotavirus gastroenteritis, which can increase hospital stays by 4-12 days. Vaccination also has an important role in the prevention of cancers with, for example, human papillomavirus or hepatitis B vaccines. Since the financial impact of cancer is high for patients, healthcare systems, and society as a whole, any cases prevented will reduce this impact. Newer vaccines, such as the herpes zoster vaccine, can provide an answer to unmet medical needs by preventing and reducing the severity of shingles and associated post-herpetic neuralgia, which are difficult conditions to treat. Thus, in the context of increasing pressure on healthcare budgets, vaccination can contribute to the sustainability of healthcare systems through reduced and more efficient use of healthcare resources.

Arbidol (ARB) is a broad-spectrum antiviral displaying activity against a number of enveloped and non-enveloped viruses. It was described as a viral entry inhibitor and shown to interact at the molecular level with lipid membranes and viral fusion glycoproteins to impede viral entry and fusion. However its mechanism of action at the cellular level remains unknown. Here, by using live-cell confocal imaging and the hepatitis C virus as a model virus, we show that ARB affects clathrin-mediated endocytosis by impeding dynamin-2-induced membrane scission. Moreover it induces the intracellular accumulation of clathrin-coated structures where viral particles are trapped. Collectively, our results shed light on the mechanistic aspects of ARB antiviral activity and suggest that ARB could prevent cell infection by viruses that enter through clathrin-mediated endocytosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We have previously reported an association between ABCB1 C3435T polymorphism and docetaxel pharmacokinetics in breast cancer patients. We therefore investigated whether these parameters could account for variations in pathological response. Five ABCB1 polymorphisms including C3435T polymorphism were analyzed in breast cancer patients receiving neoadjuvant chemotherapy with doxorubicin and docetaxel (n = 101). Pathological response was assessed using the Sataloff classification. Pharmacokinetic analysis was performed for the first course of docetaxel (n = 84). No significant association was found between ABCB1 polymorphisms or docetaxel pharmacokinetics and pathological complete response. C3435T genotype was an independent predictive factor of good response in breast (response >50 %, i.e., Sataloff T-A and T-B): OR: 4.6 (95 % CI: 1.3-16.1), p = 0.015, for TT patients versus CT and CC patients. Area under the plasma concentration-time curve (AUC) of docetaxel was the only independent predictive factor of the total absence of response in breast (Sataloff T-D): OR: 14.3, (95 % CI: 1.7-118), p = 0.015, for AUC of docetaxel <3,500 μg h/L versus ≥3,500 μg h/L. These results suggest that C3435T polymorphism and docetaxel exposure are involved in the response to neoadjuvant chemotherapy in breast cancer patients and may be useful to optimize individualized therapy.

Background: Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome., Methods: RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson's correlation, Mann-Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis., Results: Most patients had glomerulonephritis (82%). Median age was 46 years [21-87], eGFR 59 mL/min/ 1.73m2 [5-130], percentage of interstitial fibrosis 10% [0-90], glomerulosclerosis 13% [0-96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = -0.275, p = 0.038) and renal dysfunction (r = -0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%., Conclusions: Our results suggest that RI ≥ 0.65 is associated with severe interstitial fibrosis and arteriosclerosis and renal function decline. Thus, RI may contribute to identify patients at high risk of ESRD who may benefit from nephroprotective treatments.

To perform a precise evaluation of the hemolytic status of patients with sickle cell anemia (SCA), advanced red blood cell parameters provided by the last generation analyzers were investigated in a series of SCA patients. The search for precise markers of hemolysis was performed to identify if patients so exposed develop organic complications related to a postulated hemolysis-linked endothelial dysfunction. Red blood cell survival was evaluated by the ratio between mature red blood cell (RBC) and reticulocyte (RET) hemoglobin (RBC-Hb/RET-Hb). In comparison with serum lactate dehydrogenase (LDH) and total bilirubin, the log (RBC-Hb/RET-Hb) was identified as the most discriminant hematological parameter to evaluate hemolysis. Furthermore, by combining this parameter with LDH, we defined a composite variable, which we called CVar, that is highly correlated with albuminuria and might constitute a powerful new marker of risk for this complication., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available.This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases., Methods: The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2nd version (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest., Results: The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED).Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data., Conclusion: Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained "epidemiology watchers". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on "image walls" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.

The sleep apnea syndrome is a real public health problem. Improving its diagnosis using the polysomnography is of huge importance. Optisas was a visual method allowing translating the polysomnographic data into a meaningful image. In a previous paper, it was shown to bring extra information in 62% of cases. Here its capacity for displaying information of the same relevance as the one got using the classical report of the polysomnography is studied. The main result is that this capacity is weak and seems to be present only to identify the obstructive sleep apnea syndrome. Moreover this study suggests to improve the standardization of the classical report in the framework of a quality insurance process.

There is a worldwide consensus for using the diagnosis related groups (DRG) when considering hospital activity. This tool leads to the production of tables of numbers (case mix), the interpretation of which is difficult. Therefore, methods aimed at facilitating this interpretation are needed. One of such methods is the case view, i.e. a graphical representation of the case mix. It reduces, in a way, each DRG to a "pixel", the set of the DRGs being an image (the case view). The reference set should be organized according to three criteria: medical/surgical, nosological and economic. This method can be used to answer theoretical questions or to visualize activity at the level of a hospital or at the level of a department. The purpose of this paper is to present important principles inherent in this graphic representation, both at the level of the method and at the level of the user.