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Study Objectives The impact of therapy with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) has not been directly compared in patients with severe obstructive sleep apnea (OSA). The purpose of this individual participant data meta-analysis was to compare the treatment effects of CPAP and titratable MAD on sleepiness, quality of life, sleep-disordered breathing severity, and sleep structure in patients with severe OSA. Methods Randomized controlled trials (RCTs) that included severe OSA patients were identified in order to compare the impact of the two treatments. Individual data from severe OSA patients were extracted from the databases and pooled for analysis. Results Of the seven studies identified, three crossover RCT and one parallel-group RCT corresponding to 151 patients and 249 observations (125 in the CPAP treatment arm and 124 in the MAD treatment arm) were included in the analysis. Titratable MAD had a similar impact to CPAP on major patient-centered outcomes (sleepiness and quality of life). CPAP was more effective in reducing AHI and ODI. However, the two treatments had a similar impact on sleep structure with an increase of N3 and REM sleep. Finally, treatment adherence and preference were largely in favor of MAD. Conclusion This meta-analysis suggests that MAD represents an effective alternative treatment in severe OSA patients intolerant to CPAP or who prefer alternate therapy.

BackgroundThe efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial.MethodsWe conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age ≥75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (≤3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.ResultsThe trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints.ConclusionIn this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

Objectives To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58–86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45–2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. Trial registration ClinicalTrials.gov Identifier: NCT04325893 ( https://clinicaltrials.gov/ct2/show/NCT04325893 ).

The health benefits of physical exercise have been shown to be important in the prevention of cardiovascular diseases in patients with hypertension, dyslipidaemia or diabetes. However, few strategies have demonstrated efficacy and practicality in the promotion of physical exercise among this group of patients in general practice. The PEPPER clinical study is a randomised controlled trial to evaluate the efficacy over a period of 12 months, in terms of physical activity level, of an intervention based on structured information delivery, a personalised written physical activity prescription in number of steps per day, a pedometer and a pedometer logbook, in 35 to 74-year-old patients with cardiovascular risk factors. 140 patients will be recruited in 15 GP practices and randomised in the intervention group or in the control group where patients will receive verbal advice of physical exercise. The primary outcome is the change at three months in total energy expenditure measured by an accelerometer over a 7-day period. Secondary outcomes include changes at 3 and 12 months in physical activity levels (accelerometer and International Physical Activity Questionnaire), quality of life (SF-36), blood pressure, weight, waist circumference, perceived obstacles to physical activity and patient compliance with the recommended strategy. Both groups will be compared using mixed models. The results are expected at the end of 2019. If the intervention proves effective in durably increasing the level of physical activity, this strategy could be tested in a larger trial to examine its impact on cardiovascular diseases. US National Institutes of Health Clinical Trials Registry NCT02317003 , December 15, 2014.

Systemic inflammation and metabolic disorders are among the mechanisms linking obstructive sleep apnoea (OSA) and cardiovascular disease (CVD). In 109 patients with severe OSA and no overt CVD, biomarkers of inflammation (C reactive protein, interleukin-6, tumour necrosis factor-α and its receptors, adiponectin, leptin and P-selectin), glucose and lipid metabolism, and N-terminal pro-brain natriuretic peptide, were measured before and after 2 months of treatment with a mandibular advancement device (MAD) (n=55) or a sham device (n=54). MAD reduced the Apnoea–Hypopnoea Index (pTrial registration numberNCT01426607.

International audience; The American Heart Association (AHA) recommendations for diagnosing peripheral artery disease (PAD) after exercise are a decrease >20% of ankle brachial index (ABI) or >30 mm Hg of ankle systolic blood pressure (ASBP) from resting values. We evaluated ABI and ASBP values during incremental maximal exercise in physically active and asymptomatic patients. Patients (n = 726) underwent incremental bicycle tests with pre- and post-exercise recording of all four limbs arterial pressures simultaneously. Univariate and multivariate analyses were performed to define the correlation between post-exercise ABI with various clinical factors, including age. Thereafter, the population was divided into groups of age: less than 40 (G

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The “Walking Estimated-Limitation Calculated by History” (WELCH) questionnaire is a short four-item questionnaire that estimates the walking capacity of a patient in comparison with relatives, friends or people the same age. As such, it should be relatively insensitive to age, yet this has never been tested. A prospective study was performed among 525 patients presenting vascular-type claudication. Patients were grouped into quintiles of age—from quintile 1 for the youngest patients to quintile 5 for the oldest ones. Patients completed a self-administered questionnaire and then had their maximal walking time (MWT) measured on a treadmill. We estimated the coefficient of correlation, the slope and the intercept of the relationship between the WELCH score and the MWT, then the accuracy of a WELCH score under 25 to predict the ability to walk for 5 min on a treadmill. The slopes of the relationships and the correlation coefficients were not significantly different in each quintile, but a significant shift in the intercept of regressing lines was found with age. Nevertheless, the accuracy in predicting treadmill results from the WELCH score with a cut-off point of 25 was, respectively, 68.6, 72.4, 80.0, 72.4 and 73.3 % in quintiles 1, 2, 3, 4 and 5 (p = 0.45). The relationship of MWT on a treadmill and the WELCH score is slightly influenced by age, but a score superior to 25 seems to be of equal discriminatory performance in different quintiles of age to predict the ability to walk for 5 min on a treadmill. This makes this cut-off limit of interest for routine use, regardless of age.

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Data on simultaneous hemodynamic changes and pain rating estimation in arterial claudication while walking are lacking. This study was conducted to determine if a difference in transcutaneous oxygen pressure (tc pO2) exists between proximal and distal localization at pain appearance (PAINapp), maximal pain (PAINmax) and pain relief (PAINrel) in proximal or distal claudication and if a relationship exists between tc pO2 changes and pain intensity. We analyzed the pain rating (Visual Analog Scale (VAS)) to lower limb ischemia, measured with the decrease from rest of oxygen pressure (DROP) tc pO2 index during constant-load treadmill tests in patients with calf ( n = 41) or buttock ( n = 19) claudication. Calves versus buttocks results were analyzed with ANOVA tests. The R2 correlation coefficient between individual VAS versus DROP was calculated. Ischemia intensity versus pain rating changes were correlated. Significant ischemia was required for pain appearance, but pain disappeared despite the persistence of ischemia. We observed no statistical difference for DROP at PAINapp, PAINmax or PAINrel between proximal or distal claudication. A significant correlation between pain rating versus DROP was found: from PAINapp to PAINmax, R2 = 0.750 (calves) and 0.829 (buttocks), and from PAINmax to PAINrel, R2 = 0.608 (calves) and 0.560 (buttocks); p

IF 2.426; International audience; PURPOSE: There is no consensual definition of postoperative ileus (POI), which leads to a lack of reproducibility. The aims of this study were (i) to propose and evaluate a classification of postoperative ileus based on its consequences and (ii) to assess the reproducibility of the classification.METHODS: A national global survey was carried out according to the DELPHI method in order to create a classification of primary POI. The classification was subsequently tested on a cohort of patients who underwent colorectal surgery. Finally, a reproducibility test was performed in five teaching hospitals with junior and senior surgeons.RESULTS: A five-stage classification was proposed: grade A (least) to grade E (worst). For better differentiation, subcategories (D1/D2) were included. Overall, 173 patients were included who underwent colorectal surgery. Forty of them experienced primary postoperative ileus (23.1%). Grade A occurred in 10 cases, grade B in 10 cases, grade C in 14 cases, grade D1 in 2 cases, and grade D2 in 2 cases. POI-related death (grade E) occurred in 2 cases. Patients with grade A POI recovered their gastrointestinal function significantly faster than those with higher grades (p = 0.01), and were more likely to undergo laparoscopic surgery (p = 0.04). The Intraclass Correlation Coefficient (ICC) was 0.83 in the overall population, and 0.83 and 0.82 respectively in the junior and senior surgeon populations.CONCLUSION: This classification is easy to both use and reproduce. It will improve the reproducibility, evaluation, and assessment of POI. These preliminary results should be confirmed in a multi-centric international study.

Rationale: Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA).Objectives: To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA.Methods: In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention-to-treat basis. An embedded microsensor objectively measured treatment compliance.Measurements and Main Results: A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea–hypopnea index, 41 [35–53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement dev...

This study aimed to determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. We randomized patients with severe OSA and no medical history of cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on intention-to-treat bases. An embedded micro sensor objectively measured treatment compliance. 150 patients [86% males; mean (SD) age, 54 (10); median [IQR] apnea-hypopnoea index, 41 [35-53]; mean Epworth sleepiness scale, 9.3 (4.2)] were randomized to effective mandibular advancement device (n=75) or sham device (n=75). In the intention-to-treat analysis, effective mandibular advancement device therapy was not associated with an improvement in endothelial function when compared to sham device. Office and ambulatory blood pressure outcomes did not differ between the 2 groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (p vs 5.6 (2.3) h/night with sham device (p=0.006). Conclusion In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms with no effect on endothelial function and blood pressure despite high treatment compliance.

Objectif Etudier l’impact d’un traitement utilisant une orthese d’avancee mandibulaire (OAM) sur les marqueurs inflammatoires et metaboliques chez des patients atteints de SAS severe. Methodes Nous avons effectue une etude ancillaire d’un precedent essai randomise controle evaluant l’impact d’une OAM par rapport a un dispositif placebo sur la fonction endotheliale chez des patients ayant un indice d’apnees hypopnees (IAH) > 30 sans maladie CV declaree. Sur les 150 patients randomises, nous disposions de 109 echantillons disponibles pour mesurer les marqueurs d’inflammation (proteine C reactive [CRP], interleukine-6 [IL-6], factor de necrose tumorale alpha [TNF-a] et ses recepteurs R1 et R2, adiponectine, leptine et P-selectine), du metabolisme (glucose, lipides, indice HOMA) et la fraction terminale du peptide natriuretique de type B (NT-proBNP). Ces mesures ont ete effectuees avant et apres deux mois d’utilisation de l’OAM (n = 55) ou du dispositif placebo (n = 54). Resultats Dans la population de l’etude, l’IAH a l’inclusion correle positivement et significativement avec les niveaux de CRP, TNFa et P-selectine. Le temps moyen d’utilisation de l’OAM est de 6,6 h/nuit contre 6,0 h/nuit pour le dispositif simule. Le traitement par l’OAM reduit significativement l’IAH et l’indice de desaturation en oxygene, mais n’a pas d’effet sur les marqueurs circulants compare au dispositif placebo. Conclusion Chez les patients avec un SAS severe, deux mois de traitement avec une OAM reduit la severite du SAS mais n’a pas d’effets sur les facteurs inflammatoires et metaboliques malgre une forte adherence a l’OAM.

Introduction L’inflammation systemique et les atteintes metaboliques sont des mecanismes impliques dans le lien entre le syndrome d’apnees obstructives du sommeil (SAOS) et les pathologies cardiovasculaires (CV). L’objectif de cette etude etait de determiner si le traitement par orthese d’avancee mandibulaire (OAM) modifie les marqueurs inflammatoires et metaboliques chez des patients atteints de SAOS severe. Methodes Nous avons effectue une etude ancillaire d’un precedent essai randomise controle evaluant l’impact de l’OAM par rapport a un dispositif placebo sur la fonction endotheliale [1] chez des patients ayant un indice d’apnees hypopnees (IAH) > 30 sans maladie CV declaree. Sur les 150 patients randomises, 109 avaient des echantillons disponibles pour mesurer les marqueurs d’inflammation (proteine C reactive [CRP], interleukine-6 [IL-6], factor de necrose tumorale alpha [TNF-α] et ses recepteurs R1 et R2, adiponectine, leptine et P-selectine), du metabolisme (glucose, lipides, indice HOMA) et la fraction terminale du peptide natriuretique de type B (NT-proBNP). Ces mesures ont ete effectuees avant et apres deux mois d’utilisation de l’OAM (n = 55) ou du dispositif placebo (n = 54). Resultats Dans la population globale de l’etude, l’IAH a l’inclusion correle positivement et significativement avec les niveaux de CRP (p = 0,02), TNFα (p = 0,002) et P-selectine (p = 0,006). Le temps moyen d’utilisation de l’OAM est de 6,6 h/nuit contre 6,0 h/nuit pour le dispositif placebo (p = 0,10). Le traitement par l’OAM reduit significativement l’IAH (p Conclusion Chez les patients avec un SAOS severe et sans maladie CV declaree, deux mois de traitement avec une OAM reduit la severite du SAOS mais n’a pas d’effet sur les facteurs inflammatoires et metaboliques malgre une bonne observance de l’OAM.

Summary Background: Conditions that may influence heart rate recovery at 1 min of recovery from exercise (HRR1: end-exercise heart rate minus heart rate 1 min after exercise) are not fully understood. We hypothesized that the ‘importance’ (both local severity and regional diffusion) of peripheral skeletal muscle ischaemia is associated with low HRR1. Design and Methods: In 529 patients with suspected or confirmed peripheral vascular disease not receiving beta-blockers (61·4 ± 11·3 years old), we retrospectively studied the relationship of HRR1 to exercise-induced changes in transcutaneous oxygen DROP index (limb changes minus chest changes from rest). The sum of DROP indices observed on both calves and both buttocks (DROPtot) provides the unique opportunity to estimate both the severity and the diffusion of exercise-induced ischaemia on the right and left side simultaneously. It was used during a constant-load treadmill test (3·2 km h−1; 10% grade) to classify patients in quartiles, the fourth quartile representing the more ‘important’ ischaemias. Results: There was an inverse relationship between quartiles of DROPtot and HRR1, even after adjustment for heart rate reserve (Delta HR: end-exercise minus resting heart rate), age (≤ or >60 years), gender, body mass index, treadmill maximal walking distance and ankle brachial index: adjusted R = 0·629; P

International audience; Aging techniques that use the posterior or middle part of the pelvis are of interest because this part of the body is very resistant to decay. In a preliminary study, acetabular criteria correlated with age were isolated. In a second study, three acetabular criteria and four auricular surface criteria were described and it was demonstrated that it is of interest to associate these criteria. The goal of the present study was to test these criteria in a larger sample and to elaborate a standardized procedure for the use of these criteria. The study concerned 462 os coxae (hip bones) of known age and sex. All of the criteria are correlated with age. Establishing a score allows a better correlation with age with lower intra-/inter-observer variability. Seven categories of overall score corresponding to eight age groups were defined and the probabilities of belonging to an age group depending on the overall score were calculated. The first main advantage of this procedure is that it is still applicable when only some parts of the body remain. The other benefit is its ability to discriminate older people.

International audience; The aim of this study was to compare mandibular advancement device (MAd) therapy and continuous positive airway pressure (CPAP) for obstructive sleep apnoea/hypopnoea syndrome (OSAHS) after one-night polysomnographic (PSG) titration of both treatments.59 OSAHS patients (apnoea/hypopnoea index (AHI): 34±13 events·h−1; Epworth scale: 10.6±4.5) were included in a crossover trial of 8 weeks of MAd and 8 weeks of CPAP after effective titration. Outcome measurements included home sleep study, sleepiness, health-related quality of life (HRQoL), cognitive tests, side-effects, compliance and preference.The median (interquartile range) AHI was 2 (1–8) events·h−1 with CPAP and 6 (3–14) events·h−1 with MAd (p70% of patients preferring this treatment.These results support titrated MAd as an effective therapy in moderately sleepy and overweight OSAHS patients. Although less effective than CPAP, successfully titrated MAd was very effective at reducing the AHI and was associated with a higher reported compliance. Both treatments improved functional outcomes to a similar degree. One-night titration of MAd had a low negative predictive value for treatment success.

Objective: The usefulness of repeated fine-needle cytology (FNC) in thyroid nodules with benign cytology remains unknown. We analyzed the relevance of repeated FNC to detect suspicious or malignant (S/M) cytologies and carcinomas. Design: A retrospective study (1983–2004) was conducted in our endocrinology department. Methods: We reviewed the reports of 895 adequate FNC performed in 298 patients (298 nodules) during a mean follow-up of 5 years. We compared the nodules with at least one suspicious or malignant FNC (S/M nodules) with nodules with repeatedly benign (RB) FNC (RB nodules). Results: Among the nodules with initial benign cytology, we found 35 nodules with one or more later suspicious or malignant results. The interval between the first FNC and the first S/M FNC was 2.9 years. The probability for a nodule to have a repeated benign FNC decreases with time and with the number of FNC. We did not find any clinical or ultrasonographic characteristics related to an S/M cytology. Seven cancers were detected by the second or the third FNC with S/M results. The proportion of cancers among S/M nodules was similar when S/M cytology appears during the first, the second, or the third FNC. Conclusions: We suggest to repeat FNC up to three adequate samples in the follow-up of thyroid nodules so as not to miss the presence of malignant neoplasm.

Background It is commonly acknowledged that the ability to use the ankle–brachial index (ABI), a reliable way to diagnose atherosclerosis, decreases with age in the general population. The aim of this study was to determine the relationship between resting ABI and age in different populations. Methods 674 physically active participants with (active high risk, ACTHR) or without (active low risk, ACTLR) cardiovascular risk factors or/and sedentary (SED) subjects, aged 20–70 years. Systolic arterial pressure was recorded at rest and simultaneously with automatic sphygmomanometers at the arms and ankles. ABI was calculated as the ratio of the lowest, highest or mean ankle pressure to the highest arm pressure. Results Proportion of ABImin0.90) but was significantly lower in SEDHR compared with all active participants (p

To determine, by means of an ex vivo study, the effect of different NaCl concentrations on the extent of coagulation obtained during radiofrequency (RF) ablation performed using a digitally controlled perfusion device.Twenty-eight RF ablations were performed with 40 W for 10 min using continuous NaCl infusion in fresh excised bovine liver. For perfusion, NaCl concentrations ranging from 0 (demineralized water) to 25% were used. Temperature, the amount of energy, and the dimensions of thermal-induced white coagulation were assessed for each ablation. These parameters were compared using the nonparametric Mann-Whitney test. Correlations were calculated according to the Spearman test.RF ablation performed with 0.9% to 25% concentrations of NaCl produced a mean volume of coagulation of 30.7 +/- 3.8 cm(3), with a mean short-axis diameter of 3.6 +/- 0.2 cm. The mean amount of energy was 21,895 +/- 1,674 W and the mean temperature was 85.4 +/- 12.8 degrees C. Volume of coagulation, short-axis diameter, and amount of energy did not differ significantly among NaCl concentrations (p0.5). A correlation was found between the NaCl concentration and the short-axis diameter of coagulation (r = 0.64) and between the NaCl concentration and the mean temperature (r = 0.67), but not between the NaCl concentration and volume of coagulation.In an ex vivo model, continuous perfusion with high NaCl concentrations does not significantly improve the volume of thermal-induced coagulation. This may be because the use of a low-power generator cannot sufficiently exploit the potential advantage of better tissue conductivity provided by NaCl perfusion.

The goal of this paper is to explore the low-frequency oscillations of arterial pressure in humans, also called Mayer waves. We carefully describe the cardiovascular control system in order to analyse how its different components may be involved in the occurrence of sustained oscillations. We carry out an analysis of stability leading to the definition of a stability index, which we use to study the influence of each control parameter on the stability of the cardiovascular system. We show that all major components of the control system are probably implicated in the appearance of Mayer waves, substantiating recent clinical results in human as well as experimental findings in rats.

Background— We sought to identify whether transcutaneous oxygen tension (tcP o 2 ) measurements could be used to noninvasively detect lesions in the arterial network supplying blood flow to the hypogastric circulation. Methods and Results— A study was undertaken in vascular patients with suspected (PC, n=43) and not with suspected (NPC, n=34) proximal ischemia. TcP o 2 was measured on both buttocks and with a chest reference electrode. Arteriography on the right or left side was positive for stenoses (≥75%) or occlusion of one or more of the following arteries: the aorta, the common iliac arteries, or the internal iliac arteries. The arteriography was compared with the resting tcP o 2 values (REST) and with the minimal value (MIN) and maximal change from rest normalized to eventual chest changes (DROP) recorded during or after a treadmill test. REST, MIN, and DROP were, respectively, as follows in positive versus negative arteriograms (mean±SD; in mm Hg): 80.2±10.9 versus 78.6±11.5 ( P >0.05), 55.2±20.0 versus 69.9±15.8 ( P P P >0.05), 64.4±21.0 versus 75.1±14.6 ( P P Conclusions— Proximal ischemia is a frequent finding in vascular patients. TcP o 2 measurement on the buttocks during exercise is a sensitive and specific indicator for lesions in the arterial tree toward the hypogastric circulation. Potentially it could objectively assess the response to endovascular or surgical approaches to iliac lesions.

The WELCH questionnaire includes 4 items (A, B, C and D) and estimates the maximal walking time (MWT) on treadmill in patients with claudication. Its scoring was empirically defined. We aimed to test various methods for scoring to estimate whether the scoring of the WELCH could be improved or simplified.In 423 patients, we tested 8 methods (from H1 to H8) of weighing D or calculating α, β and γ in the equation MWT = (αA + βB + γC) * D.While the WELCH Pearson r was 0.639 and area under ROC curve for the ability to walk 5 minutes on treadmill was 0.795 for the reference empirical method, tested hypotheses resulted in values ranging 0.566 to 0.661 for the Pearson r values and 0.750 to 0.809 for the areas under ROC curve respectively.None of the tested methods simultaneously improved the correlation to MWT, remained simple enough to be scored by mental calculation and ranged between intuitive minimal and maximal values. The original empirical scoring seems a good compromise between accuracy and simplicity.Hintergrund: Der WELCH Fragebogen enthält 4 Elemente (A, B, C und D) und schätzt die maximale Gehzeit (MWT) auf dem Laufband bei Patienten mit Schaufensterkrankheit. Seine Punktzahl wurde empirisch definiert. Um heraus zu finden, ob die Wertung des WELCH verbessert oder vereinfacht werden könnte, haben wir verschiedene Methoden untersucht. Patienten und Methoden: Bei 423 Patienten haben wir 8 Methoden (H1 bis H8) getestet, mit Gewichtung von D oder Berechnung von α , β und γ in der Gleichung MWT = (αA + βB + γC) • D. Ergebnisse: Während der WELCH Pearson r 0.639 und die Fläche unter der ROC-Kurve für die Fähigkeit 5 Minuten auf dem Laufband zu gehen 0.795 für die empirische Methode war, reichten die Werte für die verschiedenen getesteten Methoden von 0.566 bis 0.611 für die Pearsons r Werte und 0,750 - 0,809 für die Flächen unter den Kurven. Schlussfolgerungen: Keine der getesteten Methoden verbesserte gleichzeitig die Korrelation zur MWT und blieb dabei einfach genug, um die Werte durch Kopfrechnen zu ermitteln. Das ursprüngliche empirische Scoring ist ein guter Kompromiss zwischen Genauigkeit und Einfachheit.

Purpose: This study defined how ankle arterial blood pressure measurements should be analyzed for the detection of moderate arterial disease (asymptomatic while walking). We used external iliac artery endofibrosis as a unique model of an isolated moderate arterial lesion, the role of which in exercise-related pain can be surgically proven. Methods: Patients who were ambulatory in our institutional referral center were studied. Brachial pressures, ankle pressures, and heart rate were measured simultaneously on all four limbs at rest and after maximal exercise in 108 healthy athletes and 78 patients (among 89 athletes referred for suspicion of endofibrosis) with confirmed or excluded external iliac endofibrosis. For these 78 patients, we calculated systolic ankle pressure change, ankle/brachial index, and deviation from the ankle/brachial index to heart rate regression line (DAHR) that was defined in the 108 healthy athletes. Results: In patients with endofibrosis, ankle/brachial index and ankle pressure were normal at rest. One minute after exercise, areas (mean ± SE of area) under the receiver operating characteristics curve for the diagnosis of endofibrosis were 0.91 ± 0.02, 0.91 ± 0.03, 0.95 ± 0.02, and 0.96 ± 0.02 for ankle pressure, pressure change, ankle/brachial index, and DAHR, respectively. For all criteria, area decreased with time in the recovery period. Conclusion: After heavy-load exercise, the ankle/brachial index at minute 1 should be used rather than the systolic ankle pressure value or ankle pressure change as a means of improving the efficacy of the detection of endofibrosis in athletes. A 0.66 value of the index at minute 1 after maximal exercise seems an optimal cutoff point for clinical use, providing a 90% sensitivity rate and 87% specificity rate in the diagnosis of moderate arterial lesions. At rest and after 1 minute of recovery, the ankle/brachial index to heart rate relationship should be considered to be an efficient tool for analyzing the results of pressures measurements and improving detection efficiency. (J Vasc Surg 2001;33:721-7.)

The aim of this paper is to carry out a stability analysis for periodic breathing in humans that incorporates the dynamic characteristics of ventilation control. A simple CO2 model that takes into account the main elements of the respiratory system, i.e. the lungs and the ventilatory controller with its dynamic properties, is presented. This model results in a three-dimensional non-linear delay differential system for which there exists a unique equilibrium point. Our stability analysis of this equilibrium point leads to the definition of a new explicit stability criterion and to the demonstration of the existence of a Hopf bifurcation. Numerical simulations illustrate the influence of physiological parameters on the stability of ventilation, and particularly the major role of the dynamic characteristics of the respiratory controller.

A mathematical analysis of the stability in human respiration, based on the τ-decomposition method, is conducted on a simple, but realistic CO2 model of the respiratory system. This model incorporates a two-compartment representation (lungs and tissues) for the plant and a very general class of controller. By deriving an explicit stability criterion, the stability domain of the respiratory system can be characterized. We quantify the influence of four major parameters of respiratory instability, i.e. transport delay, lung volume, and equilibrium values of lung CO2 partial pressure and controller gain. We demonstrate the existence of a bifurcation point and periodic solutions, giving some characteristics of solutions near the bifurcation point.

International audience; BACKGROUND: The published correlations between treadmill performance and the Walking Impairment Questionnaire (WIQ) score are generally fair. We hypothesized that the slope of the relationship of maximal treadmill walking time to WIQ would be lower in older than in younger patients, resulting in (1) a fair correlation in the population considered as a whole and (2) different cutoff points of the WIQ score to predict the ability to complete 5 minutes of treadmill walking in different age groups. METHODS: A 9-month prospective study was performed among patients referred for vascular-type claudication. Patients were divided into three age groups by years: 70 (group 3, n = 77). Patients self-completed the WIQ, which was corrected with a nurse, if necessary, and then completed a treadmill test. We calculated the correlation coefficient and slope of the relationship between the WIQ and maximal treadmill walking time. We used receiver operating characteristics curve analysis to estimate the accuracy of the WIQ score to determine the ability of the patients to complete 5 minutes of treadmill walking. RESULTS: Differences in slopes were significant between groups 1 vs 2 (P = .02), 2 vs 3 (P < .002), and 1 vs 3 (P < .001). The R(2) for the regression lines also tended to decrease but was only significant between two extremes (1 vs 2, P = .11; 2 vs 3, P = .07; 1 vs 3, P < .001). In patients aged

International audience; Background:If the prevalence of pulmonary embolism (PE) differs significantly between the US and Europe, this observation could reduce the generalizability of diagnostic protocols for PE derived in either location.Objective:To determine possible causes and potential clinical consequences of these PE prevalence differences.Methods:Secondary analysis of three prospectively collected multicenter samples (two French and one from the US) including 3174 European and 7940 American PE-suspected patients in Emergency departments (ED) (117 for Europe and 12 for US). Comparison of clinical features, resource use and outcomes of European- and US-suspected PE populations in ED.Results:European patients evaluated for PE were significantly older and had a higher clinical pretest probability (CPP) for PE. The final PE prevalence was significantly higher in Europe, in the overall sample (26.5% vs. 7.6%) and in each level of CPP. Suspected European patients categorized as low CPP had a higher posttest probability than US low CPP patients. Suspected US patients categorized as high CPP had a much lower posttest probability of PE than in Europe. The mean number of tests performed for one PE diagnosis was lower in Europe (7.4 vs. 21.6). Among patients diagnosed with PE, European patients had a higher mean severity of illness score and a higher PE-mortality rate (3.4% vs. 0.7%).Conclusions:Among patients suspected of a PE and those ultimately diagnosed with a PE, European patients had higher acuity, a higher pretest probability and worse outcome than US patients. The present study underscores the importance of disease prevalence for pretest probability scoring approaches and for significance interpretation of imaging tests.

International audience; OBJECTIVE: Most questionnaires do not estimate the usual walking speed of the patient, although it is well known that patients may experience apparently different walking capacities if walking slow or fast. We hypothesized that correcting the self-reported estimated walking capacity by a coefficient issued from the self-reported estimation of usual walking speed would significantly improve the correlation between questionnaire-estimated and treadmill-measured walking capacity. METHODS: Three hundred ten consecutive patients complaining of vascular-type claudication were asked to estimate their usual walking speed in comparison to people of their age (or friends or relatives) with ratings ranging from much slower (1 pt) to much faster (5 pts), in addition to the filling out of the walking impairment questionnaire (WIQ) and the estimated ambulatory capacity by history questionnaire (EACH-Q). Corrected WIQ (WIQc) and corrected EACH-Q (EACH-Qc) scores were obtained by multiplying the scores of each questionnaire by the "usual-speed" coefficient and dividing by 5. Results for questionnaire scores were compared to maximal walking time (MWT) on a treadmill. RESULTS: All but four patients self-completed the usual-speed question. Median scores (25-75 centiles) were 41% (26-59) for the WIQ and 24% (11-41) for the EACH-Q. Coefficients of correlation of the three WIQ subscales and of the EACH-Q with treadmill results were significantly improved after correction by the "usual-speed" question. Overall, WIQ (mean of the three WIQ subscales) tended to improve but did not reach significance. CONCLUSION: Correcting the self-reported estimation of walking capacity by a self-reported estimation of usual walking pace significantly improves the correlation of all WIQ subscale scores and of the EACH-Q score with treadmill measurements of capacity. This confirms the interest of speed estimation in patients with peripheral arterial occlusive disease and claudication.

A theoretical study of respiratory stability, based on a simple Co 2 model of the respiratory system, investigates each component of respiration: the plant system and the central and peripheral controller systems. Analysis of the dynamic properties of the plant leads to a simplified respiratory model for the study of the influence of the central and peripheral controller components on stability. It is shown that the central component is not involved in respiratory instability phenomena such as periodic breathing whereas the peripheral component plays a major role. The explicit analytical index of stability obtained allows definition of the conditions of occurence of periodic breathing in terms of the fundamental respiratory parameters. Moreover, this index can be used to evaluate the influence of variuous respiratory parameters on the stability of respiration.

Diabet. Med. 28, 356–362 (2011) Abstract Aim To compare symptoms and walking capacities of patients with and without diabetes reporting vascular-type claudication. Methods We recorded self-reported maximal walking distance, maximal walking distance on treadmill test (3.2 km h−1, 10% slope), exercise transcutaneous oxygen pressure DROP index [limb transcutaneous oxygen pressure (TcpO2) changes from rest minus chest TcpO2 changes from rest] and symptoms on treadmill in 230 patients with diabetes and 982 patients without diabetes. Exercise-induced proximal and distal symptoms were analysed in the perspective of underlying proximal and distal ischaemia (DROP value

Conditions that may influence heart rate recovery at 1 min of recovery from exercise (HRR1: end-exercise heart rate minus heart rate 1 min after exercise) are not fully understood. We hypothesized that the 'importance' (both local severity and regional diffusion) of peripheral skeletal muscle ischaemia is associated with low HRR1.In 529 patients with suspected or confirmed peripheral vascular disease not receiving beta-blockers (61·4 ± 11·3 years old), we retrospectively studied the relationship of HRR1 to exercise-induced changes in transcutaneous oxygen DROP index (limb changes minus chest changes from rest). The sum of DROP indices observed on both calves and both buttocks (DROPtot) provides the unique opportunity to estimate both the severity and the diffusion of exercise-induced ischaemia on the right and left side simultaneously. It was used during a constant-load treadmill test (3·2 km h(-1) ; 10% grade) to classify patients in quartiles, the fourth quartile representing the more 'important' ischaemias.There was an inverse relationship between quartiles of DROPtot and HRR1, even after adjustment for heart rate reserve (Delta HR: end-exercise minus resting heart rate), age (≤ or60 years), gender, body mass index, treadmill maximal walking distance and ankle brachial index: adjusted R = 0·629; P0·0001.During constant-load treadmill testing, DROPtot, an index of the 'importance' of exercise-induced lower-limb ischaemia, correlates with HRR1. Whether HRR1 is improved in proportion of DROPtot improvement in patients undergoing surgery or rehabilitation for peripheral artery disease is a fascinating issue for future studies.

International audience; AIM: The aim of this study was to assess the accuracy of water enema computed tomography (WECT) for the diagnosis of colon cancer. METHODS: A total of 191 patients referred for clinically suspected colon cancer were prospectively evaluated by WECT in a multicenter trial. Examination was contrast enhanced helical CT after colon filling through a rectal tube. For all the cases, final diagnosis was obtained by colonoscopy and/or surgery. CT data were interpreted both locally and at a centralized site by a specialized and general radiologist. RESULTS: Seventy-one patients were diagnosed with colon cancer. Overall, WECT sensitivity and specificity were 98.6 and 95.0%, respectively. Positive and negative predictive values were 92.1 and 99.1%, respectively. In a subgroup of 33 patients with unclean bowel, the sensitivity and specificity of WECT were 95.0 and 92.3%, respectively. The correlation between local radiologists and the specialized radiologist was excellent (Kappa = 0.87) as was the correlation between the general radiologist and the specialist (Kappa = 0.92). CONCLUSION: This prospective analysis demonstrates that WECT is an effective, safe, and simple imaging technique for the diagnosis of colon cancer and can be proposed when a strong clinical suspicion of colon cancer is present, especially in frail patients.

OBJECTIVE Ankle-to-brachial index (ABI) can be easily performed by all physicians. The Ruffier-Dickson (RD) test is an easy procedure to attain moderate exercise at the bedside for physicians who do not have an ergometer. DESIGN Retrospective analysis. SETTING Tertiary care, institutional practice. PATIENTS Fifty-three asymptomatic athletes and 22 patients suffering from unilateral pain due to histologically proven exercise-induced arterial endofibrosis (EIAE). INTERVENTION Brachial and ankle systolic blood pressures were measured in the supine position on the suspected leg in EIAE or left leg in controls, at rest (rest) and at the first minute of the recovery from incremental maximal cycle ergometer exercise (maxCE) and Ruffier-Dickson (RD) exercise tests. MAIN OUTCOME MEASURES Comparison of ABI(rest), ABI(maxCE), and ABI(RD) in discriminating patients from normal subjects, using receiver operating characteristics (ROC) curves. RESULTS Area (+/-SE of area) of ROC curve was 0.76 +/- 0.06 for ABI(rest), 0.83 +/- 0.05 for ABI(RD) (nonsignificant from rest), and 0.99 +/- 0.01 for ABI(maxCE) (P < 0.01 from ABI(RD) and P < 0.001 from ABI(rest)). An ABI(maxCE) below 0.48 was 100% specific and 80% sensitive for EIAE. For the RD test, a 100% negative predictive value was only attained for postexercise ABI values higher than 0.92. CONCLUSION ABI after maximal cycle ergometer exercise is more accurate than ABI after an RD test to search for unilateral EIAE in athletes.

International audience; ContextThe need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated.ObjectiveTo compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI.Design, Setting, and PatientsA multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005.InterventionTidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H2O) (minimal distension strategy; n=382)or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H2O (increased recruitment strategy; n=385).Main Outcome MeasuresThe primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure–free days at 28 days.ResultsThe 28-day mortality rate in the minimal distension group was 31.2% (n=119) vs 27.8% (n=107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P=.31). The hospital mortality rate in the minimal distension group was 39.0% (n=149) vs 35.4% (n=136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P=.30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P=.04) and organ failure–free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P=.04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements.ConclusionsA strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure.

Introduction The study of the posterior part of the pelvis is of interest in forensic anthropology since it is an anatomical region that is very often preserved. The Lovejoy technique, using the auricular surface has brought about many studies and attracted many authors, among them Buckberry and Chamberlain utilized the criteria described by Lovejoy and developed new methods. By using this research as a starting point, we have described acetabular criteria. The goal of this study was to test these criteria and to link them to auricular surface reading criteria, as described by Buckberry and Chamberlain. Method The study concerned 52 pelvises of known age and sex. We studied the age correlation of various criteria read at the acetabulum level and that of the auricular surface. We then went on to draw up scores and established a correlation of these scores with age. Intra- and inter-observer variability was also studied. We used the SPSS software package for statistical analyses. Discussion We were able to isolate four acetabular criteria and four auricular surface criteria which have a correlation with age. Establishing these scores (sum of criteria) allows a better age-based correlation to be obtained. Establishing an overall score, including acetabular criteria and auricular surface criteria, allows a good level of correlation to be obtained with age, with low intra- and inter-observer variability. Conclusion The study of acetabulum is of interest for the age estimation of adult subjects. The joint study of the acetabulum and the auricular surface allows a higher correlation with actual age to be obtained. This study must be broadened to include a wider sample so as to allow fine-tuning of a method.

Study design Randomized parallel-group comparative trial with a 6-month follow-up period. Objective To compare, in chronic low back pain patients, the effectiveness of a functional restoration program, including intensive physical training, occupational therapy, and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks. Summary of background data Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain, especially on return to work. Randomized Canadian and European trials had less favorable results. In France, there has been up to now no randomized study. Controlled studies suggested a positive effect of functional restoration programs. Methods Eighty-six patients with low back pain were randomized to either the functional restoration (44 patients) or the active individual therapy (42 patients) program. One person in each group never started the program. Two patients did not complete the functional restoration program, and one was lost to follow-up at 6 months. The mean number of sick-leave days in the 2 previous years was 6 months. Results After adjustment on the variable "workplace enrolled in an ergonomic program", the mean number of sick-leave days was significantly lower in the functional restoration group. Physical criteria and treatment appreciation were also better. There was no significant difference in the intensity of pain, the quality of life and functional indexes, the psychological characteristics, the number of contacts with the medical system, and the drug intake. Conclusions This study demonstrates the effectiveness of a functional restoration program on important outcome measures, such as sick leave, in a country that has a social system that protects people facing difficulties at work.

Objectives To examine whether urokinase-type plasminogen activator (uPA) and type 1 plasminogen inhibitor (PAI-1), DNA ploidy, and S-phase fraction (SPF) add supplementary prognostic information relative to stage and Fuhrman's grade in renal cell carcinoma. Methods A total of 100 patients with primary renal adenocarcinoma treated by nephrectomy were followed up for a median of 42 months. Of the 100 patients, 78 with Stage M0N0-Nx tumors were studied by multivariate analysis. The study population was dichotomized on the basis of the median cytosolic uPA and PAI-1 concentrations (30 pg/mg protein and 12.7 ng/mg protein, respectively). DNA content was measured by flow cytometry (FCM) on multiple tumor samples from each patient. DNA aneuploidy was observed in 67% of cases. The SPF was calculated for aneuploid samples. Results An FCM classification based on a combination of DNA content and SPF was obtained. High-risk patients were those with aneuploid tumors and high SPF values (greater than 1.7%) and included 23% of patients with M0N0-Nx tumors. Cytosolic uPA and PAI-1 levels were not predictive of metastasis. The stage, grade, SPF, and FCM classification were statistically significant prognostic factors in the univariate analysis, in both the overall population and the M0N0-Nx subgroup. In multivariate analysis, tumor grade and the FCM classification were the only independent predictors of disease-free survival (P = 0.018 and P = 0.046, respectively). Conclusions We defined a group of M0N0-Nx patients with aneuploid tumors and high SPF values who are at a high risk of metastasis and who may benefit from closer long-term follow-up.

It is unknown if the head-upright tilt test in patients who receive isoproterenol and nitroglycerin can identify different populations with vasovagal syncope. The aim of this study was to compare the positive or negative responses to passive tilt between isoproterenol- and nitroglycerin-sensitized upright tilt. Ninety-six patients referred for unexplained recurrent syncope underwent passive tilt (45 minutes at 70 degrees angle), which was then systematically followed, within the same session and in a random order, by a 20-minute tilt at a 70 degrees angle after administration of nitroglycerin (NTG-tilt) and 10-minute tilt at a 70 degrees angle with a continuous infusion of isoproterenol (ISO-tilt). NTG-tilt led to significantly more positive responses than passive tilt or ISO-tilt (55% vs 34% vs 42%, respectively). In the subgroup of patients with a positive response during passive tilt, the percentage of positive responses with NTG-tilt was significantly higher than with ISO-tilt (94% vs 67%). The agreement between NTG-tilt and ISO-tilt was very weak (Kappa coefficient 0.06). In the subgroup of patients with a negative response during passive tilt, the percentage of positive responses between NTG-tilt and ISO-tilt was similar (35% vs 29%). The agreement between NTG-tilt and ISO-tilt was good (Kappa coefficient 0.34). NTG-tilt led to a higher number of positive responses than ISO-tilt, especially when passive tilt outcome was positive. These 2 pharmacologic agents may identify 2 different subpopulations of patients because of their specific pharmacologic actions.

Retrospective evaluation of the prognostic value of pretreatment PSA, PSA nadir and PSA half-life compared to grade and stage after treatment of prostate cancer by radiotherapy.122 patients (19 T1 (15.6%), 31 T2a (25.4%), 26 T2b (21.3%), 20 T3a (16.4%), 19 T3b (15.6%), 7 Tx (5.7%)) treated by exclusive radiotherapy were studied with a median follow-up of 75.4 months. Treatment consisted of high energy irradiation to the prostate for 31 patients (25.4%) and to the pelvis and prostate for 91 patients (74.6%). PSA was assayed retrospectively. The influence of various parameters on the absence of laboratory failure, defined according to the ASTRO criteria, and on overall survival was studied by univariate and multivariate analysis with a Cox model.29.5% of patients did not develop any biochemical recurrence after a mean follow-up of 82 months, while biochemical recurrence occurred in 70.5% of patients after a mean interval of 5 months. Among these patients, 28 (33%) developed clinical recurrence after a mean interval of 26 months (4 to 80 months) leading to death in 17 cases. The modalities of irradiation and pretreatment PSA had no influence on the prognosis. The median PSA nadir of patients without recurrence was 0.24 ng/ml. The recurrence rate was lower for a PSA nadir less than 0.5 ng/ml for biochemical recurrence (45.5% vs 86.8%) (p0.0001) and clinical recurrence (9.1% vs 31.6%) (p0.05). On multivariate analysis, the PSA nadir (p = 0.009), PSA half-life (p0.001) and Gleason score (p = 0.004) were prognostic factors influencing survival, while PSA nadir was the only prognostic factor for biochemical recurrence (p = 0.001). Classification of patients into two groups with a significantly different prognosis according to the presence or absence of at least two favourable prognostic factors (PSA nadir less than 0.5 ng/ml, Gleason score less than 7, PSA half-life greater than 6 months) showed that the 9-year mortality rate was twofold higher in the poor prognosis group than in the good prognosis group (85.5% versus 38.6%).A nadir PSA level less than 0.5 ng/ml, a PSA half-life greater than 6 months and a Gleason score less than 7 were predictive of a low risk of biochemical recurrence and prolonged survival after treatment by exclusive radiotherapy, in our patients.