Benjamin Mahieu
email: benjamin.mahieu@inrae.fr

Michel Visalli

Arnaud Thomas

Pascal Schlich

Using Free-Comment with consumers to obtain temporal sensory descriptions of products

Keywords:

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Since it has been advocated that sensory perception is not a static phenomenon but rather a dynamic one [START_REF] Lee | Time-intensity: The temporal aspects of sensory perception[END_REF], several methods have been developed

to study the kinetic of sensations during the perception of a product. It is possible to distinguish two subcategories of temporal sensory methods: quantitative-based ones and qualitative-based ones. Among quantitative-based methods, we can mention Time-Intensity [START_REF] Lee | Time-intensity: The temporal aspects of sensory perception[END_REF], Dual-Attribute Time-Intensity [START_REF] Duizer | Dual-attribute Time-intensity Measurement of Sweetness and Peppermint Perception of Chewing Gum[END_REF], Multi-Attribute Time-Intensity [START_REF] Kuesten | Exploring taffy product consumption experiences using a multi-attribute time-intensity (MATI) method[END_REF], Progressive Profile [START_REF] Jack | Analysis of Textural Changes in Hard Cheese during Mastication by Progressive Profiling[END_REF] and Sequential Profile [START_REF] Methven | The effect of consumption volume on profile and liking of oral nutritional supplements of varied sweetness: Sequential profiling and boredom tests[END_REF]. Quantitative-based methods require a trained panel, which implies a time-consuming and possibly expensive training period before starting product evaluations.

Among qualitative-based temporal sensory methods, the two most popular are Temporal Dominance of Sensations (TDS) [START_REF] Pineau | Dominance temporelle des sensations -Codage et analyse d'un nouveau type de données sensorielles[END_REF][START_REF] Pineau | Temporal Dominance of Sensations: Construction of the TDS curves and comparison with time-intensity[END_REF] and Temporal-Check-All-That-Apply (TCATA) [START_REF] Castura | Temporal Check-All-That-Apply (TCATA): A novel dynamic method for characterizing products[END_REF]. Contrary to quantitative-based methods, TDS and TCATA can be used with consumers without specific training [START_REF] Jaeger | Number of terms to use in temporal check-all-that-apply studies (TCATA and TCATA Fading) for sensory product characterization by consumers[END_REF][START_REF] Rodrigues | Temporal dominance of sensations (TDS) panel behavior: A preliminary study with chocolate[END_REF][START_REF] Schlich | Temporal Dominance of Sensations (TDS): a new deal for temporal sensory analysis[END_REF].

During a TDS task, the subjects are asked to select among a predefined list of descriptors, which one is "dominant" at each time within a product intake [START_REF] Pineau | Dominance temporelle des sensations -Codage et analyse d'un nouveau type de données sensorielles[END_REF][START_REF] Pineau | Temporal Dominance of Sensations: Construction of the TDS curves and comparison with time-intensity[END_REF]. A descriptor is considered as dominant from its selection until another descriptor is selected as being dominant instead. TCATA adopts another rational than TDS by enabling the subjects to select several descriptors at each time within a product intake [START_REF] Castura | Temporal Check-All-That-Apply (TCATA): A novel dynamic method for characterizing products[END_REF]. In practice, subjects select a descriptor when they judge it applicable and unselect a descriptor when they judge it no longer applicable. Both TDS and TCATA share the same limitation: they rely on a predefined and necessarily short list of descriptors [START_REF] Jaeger | Number of terms to use in temporal check-all-that-apply studies (TCATA and TCATA Fading) for sensory product characterization by consumers[END_REF][START_REF] Pineau | Temporal Dominance of Sensations: What is a good attribute list?[END_REF].

Establishing a list of descriptors is very tedious and represents a critical step for the relevance of the collected data as it may affect the results of the study [START_REF] Ares | CATA questions for sensory product characterization: Raising awareness of biases[END_REF][START_REF] Pineau | Temporal Dominance of Sensations: What is a good attribute list?[END_REF][START_REF] Varela | What is dominance? An exploration of the concept in TDS tests with trained assessors and consumers[END_REF]. Furthermore, several sources of bias induced by the use of a predefined list of descriptors have been reported in the literature. The list influences the subjects by suggesting descriptors that they would not think about otherwise (Coulon-Leroy, Symoneaux, [START_REF] Coulon-Leroy | Mixed Profiling: A new tool of sensory analysis in a professional context. Application to wines[END_REF][START_REF] Kim | A novel two-step ratingbased 'double-faced applicability' test. Part 1: Its performance in sample discrimination in comparison to simple one-step applicability rating[END_REF][START_REF] Krosnick | Survey research[END_REF]. Since the list contains only a limited number of descriptors, subjects may select descriptors that are close to what they perceive but not representing exactly what they actually perceive [START_REF] Krosnick | Survey research[END_REF] and the collected data can be biased by the dumping effect [START_REF] Varela | What is dominance? An exploration of the concept in TDS tests with trained assessors and consumers[END_REF].

The first descriptors of the list (in the sense of presentation order) have a greater chance of being selected [START_REF] Castura | Do panellists donkey vote in sensory choose-all-that-apply questions?[END_REF][START_REF] Kim | A novel two-step ratingbased 'double-faced applicability' test. Part 1: Its performance in sample discrimination in comparison to simple one-step applicability rating[END_REF][START_REF] Krosnick | Survey research[END_REF][START_REF] Pineau | Temporal Dominance of Sensations: What is a good attribute list?[END_REF].

Free-Comment (FC) [START_REF] Ten Kleij | Text analysis of open-ended survey responses: a complementary method to preference mapping[END_REF], as a response to open-ended questions, has proven itself an efficient method in characterizing and discriminating sets of products both with consumers and with experts [START_REF] Lahne | Consumer sensory perception of cheese depends on context: A study using comment analysis and linear mixed models[END_REF][START_REF] Lawrence | Using the free comments method for sensory characterisation of Cabernet Franc wines: Comparison with classical profiling in a professional context[END_REF][START_REF] Ten Kleij | Text analysis of open-ended survey responses: a complementary method to preference mapping[END_REF] even out of the lab (Mahieu, Visalli, Thomas, & Schlich, 2020). As FC does not require a predefined list of descriptors, all the issues mentioned above do not longer hold. However, the FC method does not enable temporal sensory characterization.

For the products that have a relatively short tasting duration (say up to 45 seconds), collecting FC temporal descriptions in continuous time concurrently to the product intake as in TDS and TCATA is nearly impossible for practical reasons. Indeed, subjects should have first to identify the sensations they perceive within a complex signal, then think about the words that best describe these sensations and then finally transcript these words (handwriting, keyboard input, or voice recording) while staying focused on their perception. It would therefore not be reasonable to consider the data as being collected concurrently to the perception.

The recently introduced Attack-Evolution-Finish (AEF) method (Visalli, Mahieu, Thomas, & Schlich, 2020) proposes an alternative to continuous concurrent data collection. During an AEF task, subjects are asked to select retrospectively among a predefined list of descriptors which one they perceived during the so-called periods: Attack, Evolution, and Finish. The results obtained from AEF and TDS were compared in a study involving 120 consumers having evaluated five dark chocolates. AEF and TDS provided equivalent product discrimination and a very similar product characterization [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF].

The paper introduces the Free-Comment Attack-Evolution-Finish (FC-AEF), a method that integrates AEF and FC. In FC-AEF, the descriptor selection for each of the three periods (Attack, Evolution, and Finish) is replaced by an FC description, enabling a temporal sensory characterization without the issues induced by the use of a predefined list of descriptors.

The present study investigated whether consumers can successfully conduct an FC-AEF protocol at home and whether it enables the temporal characterization and discrimination of a set of products.

Material and methods

Participants

To create a situation as close as possible to an everyday consumption situation, the study took place at home with 63 naïve subjects (25 men and 38 women), 18 to 60 years old. The subjects were recruited from a population registered in the ChemoSens Platform's PanelSens database. This database has been declared to the relevant authority (Commission Nationale Informatique et Libertés-CNIL-n° d'autorisation 1148039). The subjects were consumers of dark chocolates at least once every two weeks and were rewarded for their participation in the study.

Products

Five dark chocolates provided by Barry Callebaut® were used for this study. They differed on their percentage of cocoa as well as on the origin of the cocoa used in the recipe. SDC has 54.5% of cocoa obtained from a mix of cocoa beans. BRA has 66.8% of cocoa coming from Brazil. EQU has 70.4% of cocoa coming from Ecuador. MAD has 67.4% of cocoa coming from Madagascar. SAO has 70% of cocoa coming from Sao Tomé. The chocolates were delivered to the subjects in sealed plastic containers in the form of callets (pucks of chocolates formulated for melting rather than baking).

The subjects were invited to store the chocolates in a relatively cold place so that they did not melt or alter.

Data acquisition 2.3.1. General procedure

The subjects participated in five home-based sessions on their computers running TimeSens© software 2.0 (INRAE, Dijon, France). To access the sessions, the subjects simply had to click on a link sent to them by e-mail. In each session, consumers had to evaluate and describe only one product; it lasted approximately 5 minutes. The presentation of the products (and thus the sessions) was arranged following a William Latin square design. The minimum interval between two sessions was forced to be at least 24 hours

FC-AEF task

The instructions were given to the subjects at the beginning of the first session: "You are going to taste five chocolates. Each tasting will be separated from the previous one by at least 24 hours. For each chocolate, you will be asked to describe the sensations you perceived during the tasting in the chronological order that you perceived these sensations. You will provide the descriptions using your own words." An example was given to the subjects right after the instructions: "Example: At first, I perceived this chocolate sour and soft, then after a few moments I perceived it sour, sticky and woody, and at the end of the tasting I perceived it astringent, melting and sweet". This example had the objective to inform the subjects that the same word could be used for several periods and that several different words could be used in the same period. This was underlined by the following sentence right after the example: "You can use the same words for several periods and several different words can be used in the same period". This was underlined by the following sentence right after the example: "You can use the same words for several periods and several different words can be used in the same period". Fig. 1 shows the FC-AEF data collection screen. For each product evaluation, the following instruction was given to the subjects: "What sensations did you perceive during the tasting (textures, flavors, aromas, etc.) in chronological order? (Use your own words to answer)". Three text areas corresponding to each period (Attack, Evolution, and Finish) were displayed on the screen. The text areas were organized on the screen so that the subjects filled the following sentence when describing their perception: "At first, I perceived this chocolate..., then after a few moments I perceived it..., and at the end of the tasting I perceived it..." [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF].

No particular restriction was given to the subjects on the manner of stating their descriptions. The subjects were forced to give at least one word within each period.

FC-AEF data treatment

As descriptions were collected in French, all the pre-treatments were performed in French. The analysed words resulting from the treatments have been translated into English for the present paper. The English-French correspondence of the analysed words can be found in the appendix.

All the FC-AEF data treatments were performed using R 3.5.1 (R Core Team, 2018).

The lexicon provided with IRaMuTeQ© software [START_REF] Ratinaud | IRaMuTeQ : Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires[END_REF] was used for lemmatization and part-of-speech tagging. The data of the three periods were merged before applying the following pre-treatments. This merging was done only for the pretreatments of the descriptions and to ensure that the data from each of the three periods were treated the same manner. The procedure used was the same one as described in [START_REF] Mahieu | Free-comment outperformed check-all-that-apply in the sensory characterisation of wines with consumers at home[END_REF] and summarized thereafter.

The descriptions were first cleaned, lemmatized, and filtered. Then, the words with similar meanings were grouped into latent-words relying on the chi-square-distancebased ascendant hierarchical classification. Among all the words and latent words (simply called words hereafter for simplification), only those mentioned by at least 5% of the panel for at least one same product within at least one same period were retained for further analysis.

Finally, the number of times each remaining word was cited within each period for each product was computed at the panel level. Three contingency tables, one per period, containing the citation counts of each word for each product were built. These contingency tables will be referred subsequently as "product by word contingency tables". Five contingency tables, one per product, containing the citation counts of each word for each period were built. These contingency tables will be referred subsequently as "period by word contingency tables".

Data analyses

All analyses were performed using R 3.5.1 (R Core Team, 2018).

Panel behavior

The distributions of the number of analysed words (after pre-treatments) cited by each subject, for each product and each period as well as for the three periods aggregated were computed. For a given evaluation (product × subject), the number of analysed words for the three periods aggregated corresponds to the sum of citations of analysed words of the three periods. Thus, for the aggregated data, the same word can be cited more than once per evaluation. The mean, the mode, and the standard deviation of these four distributions were computed.

Contingency tables

The eight contingency tables (a "product by word contingency table" for each of the 3 periods [A, E and, F] and a "period by word contingency table" for each of the 5 products [SDC, BRA, EQU, MAD and, SAO]) were analysed the same manner following the procedure presented in Mahieu, Visalli, and Schlich (2020) and summarized thereafter. A chi-square test using a Monte Carlo approach (1000 simulations, α = 5%) was performed to investigate the significance of the dependence between products or periods and words. If the chi-square test was significant, a correspondence analysis (CA) was applied to the contingency table. The standard CA biplot was used to display the CA results. The number of significant CA axes was determined using the Monte-Carlo tests of dependence (1000 simulations, α = 5%).

The confidence ellipses for the products or the periods coordinates in the CA space were computed with a total bootstrap procedure (1000 bootstrap samples, α = 5%) in which Procrustes rotations were performed on the significant axes. To assess relations between products or periods and words, Fisher's exact tests (α = 5%) per cell with a one-sided greater alternative hypothesis were conducted on the derived contingency table corresponding to significant axes. This contingency table is computed by reversing the CA computations on the significant axes (Mahieu, Visalli, & Schlich, 2020). To assess products or periods discrimination, a total bootstrap test (α = 5%) [START_REF] Mahieu | Free-comment outperformed check-all-that-apply in the sensory characterisation of wines with consumers at home[END_REF] was performed for each pair of products or periods on the significant axes.

Results

Panel behavior

Fig . 2 shows that the three periods had very similar distributions in terms of effective words cited. The number of effective words cited ranged from 0 to 4 (Attack period) or 5 (Evolution and Finish period). The mode of the three distributions was equal to 1, the mean was around 1.43 and the standard deviation ranged from 0.82 (Attack period) to 0.97 (Finish period). The standard deviation slightly increased from the Attack period to the Finish period.

For all periods aggregated, Fig. 2 (d) shows that the number of effective words cited for each subject and each product ranged from 0 to 10 with a mode of 4, a mean of 4.3, and a standard deviation of 1.96. 1 shows that FC-AEF presented three significant axes for the Attack and the Evolution periods and only one significant axis for the Finish period. Therefore, a product by word significant dependence was detected in each period, though less complex in the Finish period.

Product by word contingency tables

Fig. 3 shows that the first dimension of the product configuration was very similar across the three periods and mostly opposed SDC to BRA with SAO, MAD, and EQU being placed between them. This first dimension seemed to be a gradient of strength induced by the opposition of strong and slight flavors. Fig. 3 (b) shows that the second dimension of the Attack period mostly opposed MAD to the other products. This dimension seemed to be a texture gradient of hardness. Fig. 3 (b) shows that the third dimension of the Attack period mostly opposed EQU and SAO. This dimension seemed to be a gradient of sweetness associated with a second gradient of hardness. Fig. 3 (d) shows that the second dimension of the Evolution period had high similarity with the third dimension of the Attack period, mostly opposing EQU and SAO. This dimension seemed to be a gradient of sweetness but it also showed an opposition between several flavors and textures. The third dimension of the Evolution period did not show an obvious interpretation.

The product discrimination was weaker at the Finish period as compared to the Attack and Evolution periods. The five products were discriminated for the Attack and Evolution periods but not for the Finish period, where only seven pairs of products out of ten were discriminated. Fig. 3 (e) suggests that the subjects only found large differences between SDC and the other products at the finish of the product perception. These latter seem not to have any particular characteristics distinguishing them from each other at the end of the intake. Fig. 4 shows that the product discrimination into each period was driven by descriptors specific to the period. Indeed, the five products showed a kinetic of the characteristics that discriminate them from each other throughout the periods. From the Attack to the Evolution period, SDC lost its association with crunchy_hard and became associated with fat. From the Evolution to the Finish period, SDC lost its association with fat and became associated with not_bitter and gentle_slight. From the Attack to the Evolution period, BRA became associated with spicy. From the Evolution to the Finish period, BRA lost its associations with spicy, strong_intense_powerful, and bitter. At the Finish period, no significant association was found between BRA and the descriptive words.

From the Attack to the Evolution period, EQU lost its associations with not_sweet. At the Evolution and Finish periods, no significant association was found between EQU and the descriptive words. From the Attack to the Evolution period, MAD lost its associations with melting_smooth_creamy and soft. At the Evolution and Finish periods, no significant association was found between MAD and the descriptive words.

From the Attack period to the Evolution period, SAO became associated with bitter. At the Attack and Finish periods, no significant association was found between SAO and the descriptive words. The results concerning the Finish period shown by Fig. 4 tends to confirm that the subjects did not find large differences between the products at the Finish period except for SDC that was associated with four words. Indeed, the sweet and gentle_slight characteristics of SDC seem to increase over time as compared to the other products.

Period by word contingency tables

For the five products, the two axes of the CA performed on their respective period by word contingency table were highly significant. The largest of these p-values was 0.0029. This shows that for each product, the three periods were discriminated from each other. Fig. 5 shows results in line with the tests of dependence: all periods were discriminated from each other for all products. For each of them, the period configurations were similar: the first axis mostly opposed the Attack period to the Finish period while the second axis opposed the Evolution period to the Attack and Finish periods. Words related to the texture (e.g. crunchy_hard) and words related to the end of perception (e.g. long_tasting) seemed to be the most important drivers of the period configuration for all the products. However, these main drivers were associated with flavors and aromas descriptions that depended on the period for each product. Fig. 6 confirms that the period discrimination was mainly due to the texture and the end of perception descriptions. Indeed, crunchy_hard was associated with the Attack period for all the products, melting_smooth_creamy was associated with the Evolution period for all the products except BRA, and long_tasting was associated with the Finish period of all the products except SDC. This kinetic was common to all the products. Fig. 6 suggests that all products showed a temporal kinetic since the periods had different characteristics relatively to each other. SDC showed a texture kinetic, being perceived more often crunchy_hard and dry_pasty at the Attack period and then fat and melting_smooth_creamy at the Evolution period. SDC was specifically more described as not_bitter at the Finish period. BRA showed a multi-modal kinetic, being perceived more often crunchy_hard and powdery_mealy_granular at the Attack period, then woody_roasted at the Evolution period and finally lumpy and long_tasting at the Finish period. EQU showed the strongest kinetic and a very interesting one. It was perceived more often crunchy_hard, insipid, and not_sweet at the Attack period, then sweet and melting_smooth_creamy at the Evolution period and finally, bitter and long_tasting at the Finish period. MAD also presented an interesting kinetic. It was perceived more often crunchy_hard, insipid and soft at the Evolution period, then fat and melting_smooth_creamy at the Evolution period and finally, bitter, long_tasting and spicy at the Finish period. SAO only showed a slight kinetic, being perceived more often crunchy_hard at the Attack period, then melting_smooth_creamy and not_sweet at the Evolution period, and finally, long_tasting at the Finish period.

Discussion

The temporal aspect of the FC-AEF task seems to have been understood by the subjects. Indeed, the words related to texture aspects (e.g. crunchy_hard) were only mentioned in the Attack period, some sensations related to the end of the perception (e.g. long_tasting) were only mentioned in the Finish period.

The empirical results of Fig. 1 show that on average only one word and half are kept as an analysed word by period for each evaluation (subject × product). This results in an average of 4.3 analysed words per evaluation (all periods aggregated), which is not a huge increase as compared to the three words per evaluation imposed in the AEF method. However, this might be depending on the product type. It is also interesting to note that for the three periods, about 10 % of the evaluations were associated with zero analysed words. This does not mean that subject did not report descriptors, but that the pre-treatment removes these descriptors. Indeed, some descriptions were composed of only hedonic words (e.g. "good taste"), some others were composed of low cited words (e.g. "salty") and the others were composed of uninformative words (e.g. "aromas").

The results of the analyses of product by word contingency tables enabled to identify the periods of the product intake that enabled the products to be discriminated as well as the characteristics of each product leading to this discrimination. The first dimension remaining stable across all periods suggests that the main latent dimension of discrimination is independent of time for this set of products. This dimension was a gradient of strength of the chocolates and did not evolve across periods of the product intake.

The results of the CA applied on the period by word contingency tables presented a particular period configuration for all the products. The first axis systematically opposed the Attack period to the Finish period and the second axis systematically opposed the Evolution period to the Attack and Finish periods. It is mainly due to the texture and end of perception descriptions of the products. Indeed, it seems that almost all products were perceived crunchy_hard at the beginning, melting_smooth_creamy during the consumption and long_tasting at the end of the perception, at least for several subjects. This particular period configuration is likely to occur for all types of products that present an obvious kinetic of some sensations throughout the intake (e.g. textures).

Concerning the analyses of period by word contingency tables, the particular case of the product MAD is interesting: at the Attack period, two words with opposite meaning, namely crunchy_hard and soft, significantly characterized the product. It could be explained by the fact that from a subject to another, the range of time of the Attack and Evolution periods were not the same. It could also be that this product was first crunchy_hard and right after soft, leading some subjects to describe it as soft and others as crunchy_hard. Another explanation would be that, depending on their references of black chocolate, some subjects perceived it crunchy_hard and some others soft. A mixture of these phenomena is likely to be what had happened. Anyhow, investigating individual representations of the three AEF periods would be of great interest, especially the range of time considered for each AEF period.

If a temporal sensory method relying on a predefined list of descriptors had been used instead of FC-AEF to characterize this set of products, a limited number of descriptors would have been used. As the product space was the same as in [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF], the list would likely have also been the same, or at least very close. This list contains the following descriptors: Dry, Floral, Sweet, Bitter, Fat, Melting, Sour, Astringent, Woody, Sticky, Cocoa, and Fruity. Except for the descriptors Floral and Sticky, all the descriptors contained in this list were used by the subjects in their descriptions. This means that subjects were able to generate an appropriate list of words to be used for describing this set of products. However, it is interesting to note that astringent and cocoa were only sparsely employed relatively to when they are proposed in a list [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF]. Astringent maybe not a well-known word by the consumers and cocoa might sounds too obvious for several subjects when they do not belong to a list.

Compared to the pre-defined list, subjects also provided nine additional words that seem very important for the description of this set of products : crunchy_hard, insipid, strong_intense_powerful, soft, spicy, gentle_slight, powdery_mealy_granular, long_tasting and lumpy. This additional information suggests that using a predefined list would have resulted in a loss of information. It was expected that the descriptor "crunchy_hard" appeared in the descriptions since "Crunchy" was originally part of the list used in [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF]. However, several TDS studies exhibited a systematic selection of this descriptor at the beginning of the perception for every black chocolate, thus limiting the selection of other descriptors at this stage of the perception. For this reason, it was removed from the list of descriptors. Since AEF limits the description of the Attack period to a single descriptor, it was even more crucial not to include "Crunchy" in the list used in [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF] to avoid obtaining trivial descriptions of the Attack period. However, because FC-AEF does not share this limit on the number of descriptors with AEF, it was able to highlight "crunchy_hard" as a key descriptive word of first chewing cycles that discriminated between products and periods, which is a nice addition compared to AEF.

The variability of the number of terms that can be selected within each period makes FC-AEF closer to TCATA than TDS or AEF, which both forces the subjects to select one descriptor at a given time or period. However, by being retrospective, FC-AEF, as well as AEF, are different from TDS and TCATA, which are concurrent time-dependent measures. As discussed in [START_REF] Visalli | Concurrent vs. retrospective temporal data collection: Attack-Evolution-Finish as a simplification of Temporal Dominance of Sensations? Food Quality and Preference[END_REF], AEF, and thus FC-AEF too, rely on short-term memory while it is hoped that in TDS and TCATA subjects react more instinctively.

In this paper, two approaches to analyse the FC-AEF data have been proposed: product-wise and period-wise. In the product-wise approach, products are compared by period, while in the period-wise approach, periods are compared by product. These two approaches are complementary. For example, the product-wise approach informs that the product SDC was described sweeter than the other products in every period, while the period-wise approach informs that sweet was not used more often in a period than another for characterizing SDC. Depending on the problematic of the user, one of the approaches can be more appropriate than the other does. The product-wise approach is more appropriate if the study aims to investigate the differences between products at specific steps of the product perception. The period-wise approach is more appropriate if it is assumed that the temporality of the perception may be different among products.

FC-AEF has been designed for temporal sensory characterization purposes. It is a suitable method when one wants to avoid the issues induced by the use of a predefined list of descriptors and when the temporal precision provided by list-based methods like TDS or TCATA is not crucial. Using FC-AEF implies losing a part the temporal precision provided by list-based methods but as a counterpart provides several benefits: descriptions are spontaneous, rich and precise, the dumping effect and the risk of missing key information are discarded and no limitations on the number of descriptors used in the descriptions exists. Further, from a practical point of view, FC-AEF also provides some benefits: no pre-tests for establishing a list of descriptors are required and the task does not need to be explained to the consumers since it is spontaneous. FC-AEF can also be considered as a relevant alternative to static FC to raise awareness of the subjects on the temporal kinetic of their perception in every application where static FC is suitable. The benefit of FC-AEF over static FC is that it enables to highlight the kinetics of the perception if any. If no kinetics exists, then FC-AEF data can be seen as static FC data and treated as such, since it can be expected that splitting the descriptions into three temporal periods does not flaw the overall description of the products.

Conclusion

This paper introduced a new temporal sensory method called Free-Comment Attack-Evolution-Finish (FC-AEF). This method is a combination of the Free-Comment and the Attack-Evolution-Finish methods in which for each of the so-called periods (Attack, Evolution, and Finish), subjects are asked to provide a Free-Comment description instead of selecting a descriptor in a predefined list. FC-AEF was used to collect temporal sensory perceptions of dark chocolates with consumers at home. The data collected were analysed product-wise and period-wise. The product-wise analysis identified in each period the descriptors characterizing each product, while the periodwise analysis identifies for each product the descriptors generating a temporal kinetic of its perception. FC-AEF provides sensory analysts with a new tool for investigating the temporal sensory perception of products by consumers with no need of establishing a predefined list of descriptors, which enables shunting this tedious part and removing all possible issues and biases due to the use of a predefined list.

Fig. 1 :Fig. 2 :

 12 Fig. 1: FC-AEF data collection screen (translated from French)

Fig. 3 :

 3 Fig. 3: Correspondence analysis standard biplot of product by word contingency tables by period: (a) Attack axes 1-2, (b) Attack axes 3-2, (c) Evolution axes 1-2, (d) Evolution axes 3-2 and (e) Finish axes 1-2. Two products linked by a dashed line are not significantly different (total bootstrap test, α = 5%).

Fig. 4 :

 4 Fig. 4: Words by product percentages of citation across the panel for the period: (a) Attack, (b) Evolution and (c) Finish. Cells highlighted in green show the results of Fisher's exact tests (α = 5%). Grey cells correspond to words cited in another period than the one considered.

Fig. 5 :

 5 Fig. 5: Correspondence analysis standard biplot of period by word contingency tables of the product: (a) SDC, (b) BRA, (c) EQU, (d) MAD, (e) SAO.

Fig. 6 :

 6 Fig. 6: Words by period percentages of citation across the panel for the product: (a) SDC, (b) BRA, (c) EQU, (d) MAD, (e) SAO. Cells highlighted in green show the results of Fisher's exact tests (α = 5%). Grey cells correspond to words cited for another product than the one considered.

Table 1 :

 1 p-values of the test of dependence for each axis of each period Table

	Period	P-value: chi-square / axis 1	P-value: axis 2	P-value: axis 3	P-value: axis 4
	Attack	<0.001	0.0019	0.0029	0.2257

Acknowledgments

This study is part of a Ph.D. financed by the Region Bourgogne-Franche-Comté and the SensoStat Company.

The authors would like to thank Barry Callebaut© for providing the chocolate samples.


Ahidjo Ayouba

Guillaume Thaurignac

David Morquin

Edouard Tuaillon

Raisa Raulino

Antoine Nkuba

Audrey Lacroix

Nicole Vidal

Vincent Foulongne

Vincent Le Moing

Jean-Yves Jenny
email: jean-yves.jenny@chru-strasbourg.fr

Yassine Bulaid

Philippe Boisrenoult

Nicolas Bonin

Pierre Henky

Philippe Tracol

Julien Chouteau

Cyril Courtin

Claude Schwartz

Patrice Mertl

Aymard De Ladoucette

Multiplex detection and dynamics of IgG antibodies to SARS-CoV2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

RESUME

Introduction

Le traitement préventif des complications thrombo-embolique est généralement réalisé par héparine de bas poids moléculaire (HBPM) ou anticoagulants oraux directs (AOD) après prothèse totale de hanche (PTH) et de genou (PTG). Les procédures de récupération améliorée après chirurgie (RAAC) pourraient diminuer le risque thrombotique après ces interventions. L'objectif de cette étude était de comparer le risque thrombotique et le risque hémorragique dans une population non sélectionnée de PTH et PTG de première intention ayant suivi une procédure de RAAC.

Hypothèse

Le risque de complication thromboembolique postopératoire après PTH et PTG primaire était inférieur au risque de complications hémorragiques avec une procédure de RAAC.

Matériel et méthodes

Introduction

La thrombose veineuse est une complication potentiellement grave après prothèse totale de hanche (PTH) et de genou (PTG), justifiant diverses mesures prophylactiques [START_REF] Parvizi | Proximal deep venous thrombosis and pulmonary embolus following total joint arthroplasty[END_REF][START_REF] Pierce | A current review of mechanical compression and its role in venous thromboembolic prophylaxis in total knee and total hip arthroplasty[END_REF][START_REF] Lieberman | Pulmonary embolism rates following total hip arthroplasty with prophylactic anticoagulation: Some pulmonary emboli cannot be avoided[END_REF]. Si les recommandations internationales en la matière ne sont pas unanimes [START_REF] Falck-Ytter | Prevention of VTE in orthopedic surgery patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines[END_REF][START_REF] Runner | Utilization patterns, efficacy, and complications of venous thromboembolism prophylaxis strategies in primary hip and knee arthroplasty as reported by American Board of Orthopedic Surgery Part II Candidates[END_REF][START_REF] Venclauskas | European guidelines on perioperative venous thromboembolism prophylaxis: Day surgery and fast-track surgery[END_REF], une prophylaxie agressive par héparine de bas poids moléculaire (HBPM) ou anticoagulants oraux directs (AOD) est recommandée en France [START_REF] Samama | Recommandations Formalisées d'Experts. Prévention de la maladie thromboembolique veineuse postopératoire. Actualisation 2011. Texte court[END_REF], au prix d'un risque hémorragique implicitement assumé mais souvent mal évalué [START_REF] Vielpau | La recherche du juste équilibre entre efficacité et risque hémorragique[END_REF][START_REF] Cafri | Comparative effectiveness and safety of drug prophylaxis for prevention of venous thromboembolism after total knee arthroplasty[END_REF]. Toutefois l'introduction des procédures de récupération améliorée après chirurgie (RAAC) [START_REF] Husted | Fast track in total hip and knee arthroplasty -experiences from Hvidovre University Hospital, Denmark[END_REF][START_REF] Husted | Reduced length of stay following hip and knee arthroplasty in Denmark 2000-2009: from research to implementation[END_REF][START_REF] Larsen | Cost-effectiveness of accelerated perioperative care and rehabilitation after total hip and knee arthroplasty[END_REF][START_REF]Programmes de récupération améliorée après chirurgie (RAAC)[END_REF] pourrait diminuer le risque thrombotique sans modifier le risque hémorragique [START_REF] Lieberman | Pulmonary embolism rates following total hip arthroplasty with prophylactic anticoagulation: Some pulmonary emboli cannot be avoided[END_REF][START_REF] Pearse | Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism[END_REF], et de ce fait dégrader le rapport coût-bénéfice des recommandations actuelles [START_REF] Kapoor | Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: A network meta-analysis[END_REF]. L'objectif primaire de cette étude était de comparer le risque thrombotique et le risque hémorragique dans une population non sélectionnée de PTH et PTG de première intention ayant suivi une procédure de RAAC. Les objectifs secondaires étaient de tenter d'extraire des facteurs de risque thrombotiques ou hémorragiques spécifiques à la RAAC. L'hypothèse primaire de ce travail était que le risque de complication thromboembolique postopératoire après PTH et PTG de première intention était inférieur au risque de complications hémorragiques lorsque l'opéré suit une procédure de RAAC.

Matériel et méthodes

2.1.Dessin de l'étude

Une étude prospective observationnelle a été menée à l'échelle nationale, respectant les recommandations de la déclaration d'Helsinki, et après avis favorable du comité d'éthique des facultés de médecine, d'odontologie, de pharmacie, des écoles d'infirmières, de kinésithérapie, de maïeutique et des Hôpitaux de Strasbourg. Tous les centres participants ont été sélectionnés sur une base volontaire. Tous les centres avaient déjà mis en oeuvre un programme de RAAC après PTH et PTG préalablement à cette étude, et aucune modification du protocole de chaque centre n'a été faite pour cette étude. Les points communs des différents programmes de réadaptation accélérée étaient l'utilisation d'une analgésie périopératoire multimodale [START_REF] Golladay | Oral multimodal analgesia for total joint arthroplasty[END_REF][START_REF] Beverly | Essential elements of multimodal analgesia in enhanced recovery after surgery (ERAS) guidelines[END_REF], la déambulation précoce (dans les 24 heures après l'intervention) [START_REF] Pearse | Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism[END_REF][START_REF] Guerra | Early mobilization of patients who have had a hip or knee joint replacement reduces length of stay in hospital: a systematic review[END_REF] et la rééducation libre sans limitation des amplitudes articulaires ou de la mise en charge. La sortie était autorisée lorsque l'opéré était autonome pour la marche avec des douleurs maîtrisées ; la sortie directe à domicile était favorisée [START_REF] Husted | Fast track in total hip and knee arthroplasty -experiences from Hvidovre University Hospital, Denmark[END_REF][START_REF] Beverly | Essential elements of multimodal analgesia in enhanced recovery after surgery (ERAS) guidelines[END_REF].

2.2.Patients

2.3.Méthodes d'évaluation

Tous les patients ont été examinés après 3 mois, sans perdus de vue (Figure 1). La survenue

Discussion

L'hypothèse primaire a été confirmée : le risque de complication thromboembolique postopératoire après PTH et PTG de première intention était significativement inférieur au risque de complications hémorragiques lorsque l'opéré suit une procédure de RAAC. Un enseignement de cette étude est que les complications thrombo-emboliques cliniquement symptomatiques après PTH et PTG suivant une procédure de RAAC sont devenues exceptionnelles, avec un taux de 0,7%. Ce taux très faible est notablement inférieur à celui publié après des procédures de rééducation conventionnelles [START_REF] Vielpau | La recherche du juste équilibre entre efficacité et risque hémorragique[END_REF][START_REF] Kulshrestha | DVT Prophylaxis after TKA: Routine anticoagulation vs risk screening approach -A randomized study[END_REF][START_REF] Aynardi | Outpatient surgery as a means of cost reduction in total hip arthroplasty: A case-control study[END_REF][START_REF] Odeh | Risk-stratified venous thromboembolism prophylaxis after total joint arthroplasty: Aspirin and sequential pneumatic compression devices vs aggressive chemoprophylaxis[END_REF][START_REF] Colwell | A mobile compression device for thrombosis prevention in hip and knee arthroplasty[END_REF] pour des populations pourtant comparables et avec un traitement prophylactique similaire (tableau 6).

Notamment, une étude française sur une population similaire avec une thromboprophylaxie conventionnelle retrouvait un taux de complications thrombo-emboliques de 1,3% après PTH et de 2,8% après PTG [START_REF] Samama | Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study[END_REF]. D'autres études ont rapporté des résultats comparables après des procédures de RAAC similaires [START_REF] Grosso | Decreasing length of hospital stay and postoperative complications after primary total hip arthroplasty: A decade analysis from 2006 to 2016[END_REF], parfois même avec un traitement prophylactique allégé [START_REF] Anderson | Aspirin or Rivaroxaban for VTE prophylaxis after hip or knee arthroplasty[END_REF] ou raccourci [START_REF] Jørgensen | Thromboprophylaxis only during hospitalisation in fast-track hip and knee arthroplasty, a prospective cohort study[END_REF] (Tableau 3). Enfin, l'aspirine pourrait retrouver une place dans le traitement antithrombotique prophylactique [START_REF] Anderson | Aspirin or Rivaroxaban for VTE prophylaxis after hip or knee arthroplasty[END_REF]. Tous ces résultats suggèrent que les procédures de RAAC entraînent par elles-mêmes une diminution du risque de complication thrombo-embolique [START_REF] Pearse | Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism[END_REF][START_REF] Grosso | Decreasing length of hospital stay and postoperative complications after primary total hip arthroplasty: A decade analysis from 2006 to 2016[END_REF], et ce sans doute grâce au lever précoce qui réactive précocement la pompe musculaire [START_REF] Pearse | Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism[END_REF], car les autres composantes des procédures de RAAC, notamment l'analgésie multimodale non morphinique, ne sont pas réputées pour influencer le risque thrombo-embolique postopératoire. On peut même émettre l'hypothèse que la réalisation de ces gestes en ambulatoire, encore exceptionnelle en France à ce jour mais sans doute en devenir, pourrait encore diminuer ce risque [START_REF] Cassard | Outpatient total knee arthroplasty: Readmission and complication rates on day 30 in 61 patients[END_REF][START_REF] Crawford | Low complication rates in outpatient total knee arthroplasty[END_REF], mais la présente étude ne permet pas d'analyser ce point. En tout état de cause, en l'absence de toute complication identifiée spécifique aux procédures de RAAC [START_REF] Grosso | Decreasing length of hospital stay and postoperative complications after primary total hip arthroplasty: A decade analysis from 2006 to 2016[END_REF], tous ces éléments confirment que ces procédures devraient aujourd'hui être le traitement postopératoire standard après PTH et PTG de première intention. Les difficultés de mise en place de ces procédures, essentiellement d'ordre organisationnel mais aussi liées aux obstacles psychologiques au changement, ne doivent pas être de nature à freiner cette évolution [START_REF] Vendittoli | Enhanced recovery short-stay hip and knee joint replacement program improves patients outcomes while reducing hospital costs[END_REF].

L'autre enseignement est que les complications hémorragiques étaient significativement plus fréquentes que les complications thrombo-emboliques, avec un taux de 1,7%. Ce taux n'est pas, en valeur absolue, rédhibitoire, et est similaire à d'autres publications récentes [START_REF] Vielpau | La recherche du juste équilibre entre efficacité et risque hémorragique[END_REF][START_REF] Kulshrestha | DVT Prophylaxis after TKA: Routine anticoagulation vs risk screening approach -A randomized study[END_REF][START_REF] Odeh | Risk-stratified venous thromboembolism prophylaxis after total joint arthroplasty: Aspirin and sequential pneumatic compression devices vs aggressive chemoprophylaxis[END_REF][START_REF] Nam | The use of Warfarin for DVT prophylaxis following hip and knee arthroplasty: How often are patients within their target INR range?[END_REF]. On ne peut donc pas suspecter une modification du risque hémorragique par les procédures de RAAC. Mais la diminution de la fréquence des complications thromboemboliques modifie évidemment le rapport coût-efficacité de la prophylaxie par HBPM ou AOD, car ces complications requièrent de façon très fréquente un traitement propre, et parfois une réintervention [START_REF] Pujol | Unplanned return to theater: A quality of care and risk management index?[END_REF], qui retentissent sur la rapidité de récupération et potentiellement sur le résultat final de l'intervention. Il faut notamment évoquer les incidents cicatriciels avec écoulement prolongé, favorisés par le traitement anticoagulant, et qui font le lit de l'infection de site opératoire avec toutes les difficultés thérapeutiques bien connues [START_REF]Prothèse de hanche ou de genou : diagnostic et prise en charge de l'infection dans le mois suivant l'implantation[END_REF]. Il faut également mentionner les difficultés de compliance au traitement, notamment après prescription d'AOD, qui majorent potentiellement les risques de complications iatrogènes [START_REF] Lebel | Oral thromboprophylaxis following total hip replacement: The issue of compliance[END_REF]. Les résultats de la présente étude suggèrent donc de réévaluer le rapport coût-bénéfice des traitements préventifs par HBPM ou AOD après PTH et PTG suivant une procédure de RAAC [START_REF] Aynardi | Outpatient surgery as a means of cost reduction in total hip arthroplasty: A case-control study[END_REF]. Il semble souhaitable d'individualiser la prophylaxie antithrombotique postopératoire selon les risques respectifs de thrombose veineuse et de saignement postopératoire [START_REF] Venclauskas | European guidelines on perioperative venous thromboembolism prophylaxis: Day surgery and fast-track surgery[END_REF][START_REF] Kulshrestha | DVT Prophylaxis after TKA: Routine anticoagulation vs risk screening approach -A randomized study[END_REF][START_REF] Parvizi | Individualized risk model for venous thromboembolism after total joint arthroplasty[END_REF]. L'utilisation de l'aspirine pourrait représenter un compromis acceptable chez les patients sans facteurs de risques thrombotiques majeurs [START_REF] Venclauskas | European guidelines on perioperative venous thromboembolism prophylaxis: Day surgery and fast-track surgery[END_REF][START_REF] Odeh | Risk-stratified venous thromboembolism prophylaxis after total joint arthroplasty: Aspirin and sequential pneumatic compression devices vs aggressive chemoprophylaxis[END_REF][START_REF] Anderson | Aspirin or Rivaroxaban for VTE prophylaxis after hip or knee arthroplasty[END_REF][START_REF] Cassard | Outpatient total knee arthroplasty: Readmission and complication rates on day 30 in 61 patients[END_REF][START_REF] Jenny | European guidelines on perioperative venous thromboembolism prophylaxis: Aspirin[END_REF].

Mais la littérature ne permet pas de préconiser un protocole particulier [START_REF] Jørgensen | Thromboprophylaxis only during hospitalisation in fast-track hip and knee arthroplasty, a prospective cohort study[END_REF][START_REF] Cassard | Outpatient total knee arthroplasty: Readmission and complication rates on day 30 in 61 patients[END_REF][START_REF] Aaos | Venous Thromboembolic Disease in Elective TKA and THA (Prevention)[END_REF], et le choix doit donc se faire de façon individuelle en analysant les risques respectifs de l'intervention et ceux liés au patient [START_REF] Venclauskas | European guidelines on perioperative venous thromboembolism prophylaxis: Day surgery and fast-track surgery[END_REF]. Mais les critères de ce choix ne sont actuellement pas validés.

Aucun facteur de risque de la survenue d'une complication thrombo-embolique ou hémorragique spécifique aux procédures de RAAC n'a pu être mis en évidence. De multiples facteurs de risque de complications thrombo-emboliques ont été évoqués dans la littérature : âge élevé, sexe féminin, obésité, antécédents personnels ou familiaux d'évènement thromboembolique, cancer évolutif, temps de garrot, durée de l'intervention… [START_REF] Zhang | Risk factors for venous thromboembolism after total hip and total knee arthroplasty: a meta-analysis[END_REF][START_REF] Plante | Analysis of contributing factors influencing thromboembolic events after total knee arthroplasty[END_REF][START_REF] Masrouha | Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral vs unilateral total knee arthroplasty[END_REF]. Parallèlement, de multiples facteurs de risque de complication hémorragique ont été décrits : âge élevé, poids faible ou élevé, insuffisance rénale… [START_REF] Masrouha | Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral vs unilateral total knee arthroplasty[END_REF][START_REF] Fuji | Incidence of venous thromboembolism and bleeding events in patients with lower extremity orthopedic[END_REF]. Mais aucun de ces facteurs n'a eu d'influence significative sur le taux de complications thrombo-embolique ou hémorragique dans cette étude. Ceci n'est guère surprenant en raison de la faible incidence de ces complications. Un effectif beaucoup plus important aurait été nécessaire, mais ceci ne semble pas réalisable en dehors d'une méta-analyse.

Cette étude présente plusieurs limitations. 1) Il s'agit d'une étude multicentrique purement observationnelle, incluant de ce fait des biais potentiels non contrôlés. Par exemple, les protocoles de RAAC étaient potentiellement variables selon les centres, et les taux de complications observés pourraient être le reflet de ces pratiques différentes plutôt que de l'application de la RAAC elle-même. Cependant les principes directeurs étaient identiques et appliqués de façon systématique dans tous les centres. 2) Les complications ont pu être recensées et leur gravité appréciée de façon différente dans les centres participants ; mais un critère de jugement univoque ou par un observateur unique semble irréaliste. Cette étude représente toutefois une véritable analyse des pratiques des équipes ayant participé, avec un recrutement universitaire et libéral dans des grandes agglomérations ou des villes moyennes, qui pourrait être un reflet acceptable de la pratique nationale française. 3) L'effectif reste limité pour une analyse de la survenue d'événements à faible probabilité, mais a été calculé comme suffisant pour détecter l'effet recherché. Ceci ne remet pas en cause le caractère significatif de la différence observée, et ne serait un réel inconvénient que si aucune différence n'avait été observée. Mais le faible effectif peut expliquer la négativité de la recherche des facteurs de risque de complication thrombo-embolique ou hémorragique.

Conclusion

La prescription d'HBPM ou d'AOD après PTH ou PTG de première intention avec procédure de RAAC pourrait exposer à un risque hémorragique significativement supérieur au risque thrombotique. Une individualisation de la prophylaxie antithrombotique dans le cadre de la RAAC semble donc souhaitable, mais ses critères restent à définir [START_REF] Venclauskas | European guidelines on perioperative venous thromboembolism prophylaxis: Day surgery and fast-track surgery[END_REF].

Financement : Aucun financement n'a été reçu pour cette étude. surgery: a retrospective analysis of a Japanese healthcare database. J Orthop Surg Res 2017;12:55. doi: 10.1186/s13018-017-0549-4.

LEGENDES DES FIGURES

  Une étude prospective observationnelle a été menée à l'échelle nationale. Tous les patients opérés d'une PTH ou d'une PTG primaire unilatérale dans les 11 centres participants entre octobre 2016 et octobre 2017 ont été inclus et suivis pendant 3 mois. La survenue d'une complication thrombo-embolique ou d'une complication hémorragique a été colligée. Aucun patient n'a été perdu de vue à 3 mois. Résultats Sur les 1.110 PTH, 5 complications thrombo-emboliques (0,4%) et 19 complications hémorragiques (1,7%) ont été recensées (1,7%). Sur les 839 PTG, 9 complications thromboemboliques (1,0%) et 14 complications hémorragiques (1,7%) ont été recensées. Il n'existait pas de différence significative entre le taux de complications thrombo-emboliques et les taux de complications hémorragiques après PTH et PTG. Le taux global de complications hémorragiques (1,7%) était significativement supérieur au taux global de complications thrombo-emboliques (0,7%) (p=0,005). Ceci était également observé pour les PTH individuellement (p=0,004) mais par pour les PTG. Discussion L'enseignement principal de cette étude que les complications hémorragiques étaient significativement plus fréquentes que les complications thrombo-emboliques après implantation d'une PTH ou d'une PTG avec une procédure de RAAC. Les résultats de la présente étude suggèrent donc de réévaluer le rapport coût-bénéfice des traitements préventifs par HBPM ou AOD dans cette situation. Niveau de preuve : IV ; Etude prospective de cohorte sans groupe contrôle Mots-clés : Prothèse totale de hanche, Prothèse totale de genou, complication thromboembolique, prophylaxie, hémorragie

  d'une des complications suivantes a été notée : Complications thrombo-emboliques : -thrombose veineuse proximale ou distale avec symptômes cliniques et confirmation échographique ; -embolie pulmonaire avec symptômes cliniques et confirmation à l'imagerie scanographique ou IRM. Complications hémorragiques : -hématome du site opératoire nécessitant une modification thérapeutique (renforcement du traitement antalgique, modification de la rééducation, modification du traitement anticoagulant ou anti-agrégant, ponction, drainage percutané, évacuation chirurgicale ; -hémorragie extériorisée du site opératoire nécessitant une modification thérapeutique (cf. ci-dessus) ; -écoulement cicatriciel non tari spontanément après 5 jours d'évolution ; -hémorragie d'un autre site (digestive, oculaire, cérébrale…) ; -nécessité d'une transfusion homologue quel qu'en soit le motif. Le traitement éventuel de la complication et son influence sur l'évolution ultérieure ont également été colligés. 2.4.Analyse statistique Les calculs statistiques ont été effectués sur un tableur Excel™ (Microsoft, Issy-les-Moulineaux, France) avec l'extension XLSTAT™ (Addinsoft, Bordeaux, France). Les effectifs de l'étude ont été calculés avec les données de base suivantes : risque α = 0,05, risque β = 0.20, fréquence attendue des complications hémorragiques = 4%, différence minimale cliniquement significative = 1%, donnant un effectif minimal de 798 observations. Les taux de complications thrombo-emboliques et hémorragiques ont été comparés par un test de Chi² pour la population globale puis séparément pour les PTH et les PTG. L'influence des variables pronostiques potentielles choisies a priori et listées dans les tableaux 1 et 2, ainsi que l'influence du type de traitement préventif administré ont été analysées. Les données ont été comparées entre les différents centres pour rechercher un effet centre éventuel. Les données catégorielles ont été analysées par un test de Chi². Tous les tests statistiques ont été réalisés au seuil de 5%.

  3. RESULTATS Sur les 1.110 PTH, 5 complications thrombo-emboliques ont été recensées (0,4%) (2 embolies pulmonaires non mortelles et 3 thromboses veineuses), toutes traitées médicalement et sans retentissement sur l'évolution ultérieure. Dix-neuf complications hémorragiques ont été recensées (1,7%) (10 hématomes significatifs dont 5 ont nécessité une évacuation chirurgicale et 3 se sont compliqués d'infection, 9 anémies avec 4 transfusions). Sur les 839 PTG, 9 complications thrombo-emboliques ont été recensées (1,0%) (4 embolies pulmonaires non mortelles et 5 thromboses veineuses), toutes traitées médicalement sans retentissement sur le résultat final. Quatorze complications hémorragiques ont été recensées (1,7%) (8 hématomes dont 4 ont nécessité une évacuation chirurgicale et 2 se sont compliqués d'infection, 6 anémies avec 5 transfusions). Le taux global de complications hémorragiques (1,7%) était significativement supérieur au taux global de complications thrombo-emboliques (0,7%) (p=0,005). Ceci était également observé pour les PTH individuellement (p=0,004) mais par pour les PTG. Il n'existait pas de différence significative entre le taux de complications thrombo-emboliques et les taux de complications hémorragiques après PTH et PTG. Aucun des facteurs de risque analysés n'a eu une influence significative sur le risque de complications thrombo-emboliques (tableau 3) et hémorragiques (tableau 4), sauf la prise d'un traitement anti-agrégant plaquettaire ou anticoagulant précédent l'intervention sur le risque hémorragique (tableau 4). Notamment, le type de traitement préventif administré et l'utilisation ou non d'acide tranexamique n'avait pas d'influence significative (tableaux 3 et 4). Il n'existait par ailleurs pas de différence significative entre les taux de complications thrombo-emboliques et hémorragiques des différents centres participants (tableau 5).

Figure 1 : 1 Table1:

 11 Figure 1 : Déroulement de l'étude

  Prothèse totale de hanche, PTG : Prothèse totale de genou, IMC : Indice de Masse Corporelle RAAC : Procédures de récupération améliorée après chirurgie.

	Tableau 2 : Comorbidités significatives Tableau 3 : Facteurs de risque de complications thrombo-emboliques. Tableau 4 : Facteurs de risque de complications hémorragiques Tableau 5 : Comparaison des taux de complications thrombo-emboliques et hémorragiques Tableau 6 : Données de la littérature.
	dans les centres participants Auteurs Année de		PTH (N=1.110) Complication PTG (N=839) Pas de complication Global (N=1.949) Signification Complication Pas de complication Signification Procédure Complications Complications Remarques
	Age > 75 ans (nombre, Centre Nombre de cas 300 (27%) thrombo-embolique 261 (31%) thrombo-embolique 561 (29%) hémorragique hémorragique Complications Complications publication thrombo-hémorragiques
	pourcentage) Sexe féminin (nombre, pourcentage) Age ≥ 75 ans Age < 75 ans Sexe féminin Sexe masculin Age ≥ 75 ans Age < 75 ans Poids ≤ 40 kg ou ≥ 120 kg 40 kg < Poids < 120 kg Samama et al. 2007 [24]	611 (55%) Conventionnelle 10 (1%) 4 (1%) 11 (1%) 3 (0,4%) 15 (2%) 18 (1%) thrombo-emboliques 525 (63%) 610 (99%) 1.136 (58%) 1325 (99%) 1125 (99%) 810 (99,6%) 599 (98%) NS NS NS emboliques hémorragiques 1317 (99%) 0 33 (2%) 61 (100%) 1855 (98%) (nombre -1,8% 1,0% 1080 cas -(nombre -NS pourcentage) pourcentage) PTH + PTG
	IMC > 25 kg/m² (nombre, IMC ≥ 25 kg/m² Insuffisance rénale Amiens Kulshrestha et 2013	743 (67%) 638 Conventionnelle 11 (1%) 1 (%) 2,1% 666 (79%) 4 (0,6%)	1.409 (72%) 1427 (99%) 66 (99%) NS NS 8 (1,3%) 6,4% 900 cas -
	pourcentage) IMC < 25 kg/m² Pas d'insuffisance rénale Annecy Kumar [20]		111		3 (1%) 32 (2%)		0	508 (99%) 1850 (98%)	0	PTG
	Poids < 40 kg ou > 120 kg Cancer évolutif Intervention préalable Brest Aynardi et al. 2014	24 (2%) 36 Ambulatoire vs	0 3 (3%)	0	20 (2%) 0	0 91 (97%)	44 (2%) 0 197 cas -NS NS
	(nombre, pourcentage) Pas de cancer évolutif Pas d'intervention préalable Cavaillon [21]	14 (1%) 29 (2%) Conventionnelle 161	4 (2,5%)	1935 (99%) 1826 (98%) 5 (3,1%)	PTH
	Cancer évolutif (nombre, Antécédent thrombo-embolique Traitement anti-agrégant plaquettaire ou 0 (0%) Lyon 192 Colwell et al. [23] 2014 Conventionnelle 11 (3,0%) 0 (0%) 2 (1,0%) 0 (0%) 0,9%	0 (0%) p = 0,03 NS 1 (0,5%) 15 (100%) 351 (97,0%) 3060 cas -
	pourcentage) Pas d'antécédent thrombo-embolique anticoagulant préalable Lyon CHU	42	)	14 (1%)	584 (70%) 0	1.487 (76%) 1920 (99%) 0 PTH + PTG
	ASA Garrot (PTG) 1-2-3 Pas de traitement anti-agrégant plaquettaire (nombre, 228 -667 -215 4 (1%) 22 (1,4%) 90 -551 -198 263 (99%) 318 -1.218 -413 NS 1565 (98,6%) Saint-Louis 31 0 0 Odeh et al. [22] 2016 Conventionnelle 1,5% 0,5% 2611 cas -
	HBPM -AOD (nombre, pourcentage) Strasbourg Pas de garrot (PTG) ou anticoagulant préalable		910 -200 (21% -60% -183	5 (1%)	741 -98 (11% -66% -0	1651 -298 1 (0,5%) (16% -63% -21%) 567 (99%) PTH + PTG
	pourcentage) Début thromboprophylaxie à J0 de la Traitement anti-agrégant plaquettaire ou (82% -18%) 681 -429 (61% -39%) 19%) Prophylaxie par HBPM Jørgensen et al. 2013 RAAC Antécédent thrombo-embolique ou anticoagulant préalable Pas d'administration d'acide tranexamique Versailles 266 (nombre, 17 (2%) anticoagulant préalable Prophylaxie par AOD Strasbourg CHU 124 [27] Pas de traitement anti-agrégant plaquettaire Administration d'acide tranexamique Toulouse 165 Anderson et al. 2018 RAAC	(88% -12%) 527 -312 (63% -37%) 27 (1,6%) 0 1624 (98,4%) (85% -15%) 1208 -741 (62% -38%) 362 (100%) NS NS 0,4% 4924 cas -23%) 5 (1,4%) 350 (98,6%) 4 (1,5%) 9 (3,4%) 9 (1%) 6 (1,7%) 0 4 (3,2%) 349 (98,3%) PTH + PTG 26 (1%) 14 (0,9%) 1573 (99,1%) 28 (1,8%) 1566 (98,2%) 0 5 (3,0%) NS 0,7% 0,4% 3424 cas -
	(nombre, pourcentage) Prophylaxie par HBPM HBPM : Héparines de bas poids moléculaire, AOD : Anticoagulants oraux directs 12 (0,7%) 1639 (99,3%) Total 1949 14 (0,7%) 33 (1,7%) pourcentage) [23] PTH + PTG NS
	Administration d'acide Garrot (nombre, Prophylaxie par AOD Signification Grosso et al. [25] 2019		848 (76%) Sans objet RAAC	746 (89%) 321 (38%) NS 0,4% 2 (0,7%)	1.612 (83%) 321 (29%) NS 296 (99,3%) 86099 cas -
	tranexamique (nombre, pourcentage) Administration d'acide tranexamique			11 (0,7%)	1583 (99,3%)	NS PTH
	pourcentage) Traitement anticoagulant Pas d'administration d'acide tranexamique 258 (23%) Présente série 2020 RAAC	104 (12%) 0,4% 3 (0,8%)	362 (19%) 352 (99,2%) 1,7% 1949 cas -
	PTH: Prothèse totale de hanche, PTG : Prothèse totale de genou, IMC : Indice de Masse ou anti-agrégant habituel PTG : Prothèse totale de genou, IMC : Indice de Masse Corporelle. HBPM : Héparines de bas PTH + PTG
	Corporelle. HBPM : Héparine de bas poids moléculaire. AOD : Anticoagulants directs oraux. (nombre, pourcentage) poids moléculaire, AOD : Anticoagulants oraux directs PTH:
	PTH: Prothèse totale de hanche, PTG : Prothèse totale de genou, IMC : Indice de Masse
	Corporelle.

Table 2 :

 2 Sensitivity, specificity and accuracy of the xMAP assay to detect IgG to SARS-CoV2 antigens in 138 samples; 77 negative control samples and 61 samples from COVID-19 patients ≥ days after onset of symptoms

			Spike	Nucleocapsid (NC)	Spike+ and NC+
		≥ Day14	95% CI	≥ Day14	95% CI	≥ Day14	95% CI
		(n=138)		(n=138)		(n=138)
	Sensitivity (%)	100.0	92.7-100	100.0	92.7-100	100.0	94.-100
	Specificity (%)	100.0	94.2-100	98.7	92.2-100	100.0	95.2-100
	Accuracy (%)	100.0	100.0-100	99.9	99.7-100	100.0	97.3-100
	PPV (%)	100.0	94.1-100	98.4	91.4-99.7	100.0	94.1-100
	NPV (%)	100.0	95.2-100	100.0	95.2-100	100.0	95.2-100

Table 3 :

 3 Sensitivity of the xMAP assay to detect IgG anti SARS-CoV2 antigens stratified by time since symptoms onset

	Time since symptoms	N	IgG anti-NC Positive	IgG anti-SP	NC+SP+
	onset		n positive (%)	n positive (%)	n positieve (%)
	≤ Day 7	10	5 (50)	5 (50)	3 (30)
	Day8-Day13	19	15 (78.9)	16 (84.2)	15 (78.9)
	After Day13	61	61 (100)	61 (100)	61(100)
	Total	90	81 (90)	82 (91.1)	79 (87.7)

Table 5 :

 5 Cross-reactions of 61 SARS-CoV2 convalescent samples (> 2weeks after onset of symptoms) with SARS-CoV1 and MERS-CoV antigens.

		N positive/N tested	%
	SARS-CoV1-NC+	61	100
	SARS-CoV1-SP+	28	45.9
	MERS-CoV-NC+	2	3.3