The Carcinologic Handicap Index: validation of the upgraded version and ability to highlight head and neck cancer patients' needs

The first version of the Carcinologic Handicap Index (CHI) assessed the symptoms presented by ENT patients and the impact on their quality of life (Balaguer, 2017). But this version got two issues : missing domains, and lack of emerging priorities for the patients in terms of care. The objective of this study is to validate the complete version of the CHI, and to evaluate the link between the scores of the CHI and the patients' needs. Methods: We added two new dimensions to the 9 of the first version of the CHI : neck and shoulders limitation, and psychosocial impact due to physical modifications. We included 71 patients with head and neck cancer consulting for a follow-up consultation in ENT between november 2017 and march 2018, with no restriction about location, tumor size or treatment received. Our controls were 36 healthy subjects. The cases and controls had to fill the completed version to assess the convergent validity, and also a Visual Analog Scale for each dimension (criterion validity). The comparison between cases and controls allowed us to assess the structural validity. They had to fill once again the CHI after 7 days to evaluate the temporal validity. Finally, to study the link between the scores of the different dimension of the CHI and the patients's needs, the subjects had to rank the 11 dimensions of the CHI from the most troublesome to the least. Results: our new dimensions shows good convergent validity (Spearman's coefficient of correlation between 0.35 and 0.73) and discriminant validity (r<0.30). A factorial analyzis confirms the structure in 11 domains. The structural validity shows a difference between cases and control (p<0.001). Strong correlations between CHI score and VAS are found with a coefficient r=0.74 for « physical modification » and r=0.68 for « neck and shoulders limitations ». The reliability is high, with a Cronbach's alpha higher than 0.72 for the new dimensions. Finally, the temporal validity is correct with correlations higher than 0.67 between the 2 completions of the CHI. The ranking of dimensions differs the scores for 54 % of the subjects (confidence intervals of intraclass correlations). But, if we only consider the 5 top-scored domains in the CHI, a match exists with 3 or 4 top-ranked domains for 77% of the subjects. Discussion: the two new dimensions presents good psychometric qualities and assess dimensions frequently impacted by the pathology in this population. By considering the 5 top-scored dimensions of the CHI, care-team members can enlight which domains are the more important for the patients in terms of care strategy, to reduice the impact in their everyday life. This completed versions needs to be translated, and compared to a Patients Concerns Inventory

Evidence for an RNA Polymerization Activity in Axolotl and Xenopus Egg Extracts

We have previously reported a post-transcriptional RNA amplification observed in vivo following injection of in vitro synthesized transcripts into axolotl oocytes, unfertilized (UFE) or fertilized eggs. To further characterize this phenomenon, low speed extracts (LSE) from axolotl and Xenopus UFE were prepared and tested in an RNA polymerization assay. The major conclusions are: i) the amphibian extracts catalyze the incorporation of radioactive ribonucleotide in RNase but not DNase sensitive products showing that these products correspond to RNA; ii) the phenomenon is resistant to α-amanitin, an inhibitor of RNA polymerases II and III and to cordycepin (3′dAMP), but sensitive to cordycepin 5′-triphosphate, an RNA elongation inhibitor, which supports the existence of an RNA polymerase activity different from polymerases II and III; the detection of radiolabelled RNA comigrating at the same length as the exogenous transcript added to the extracts allowed us to show that iii) the RNA polymerization is not a 3′ end labelling and that iv) the radiolabelled RNA is single rather than double stranded. In vitro cell-free systems derived from amphibian UFE therefore validate our previous in vivo results hypothesizing the existence of an evolutionary conserved enzymatic activity with the properties of an RNA dependent RNA polymerase (RdRp)

Acoustic-phonetic decoding for speech intelligibility evaluation in the context of Head and Neck Cancers

International audienceIn addition to health problems, Head and Neck Cancers (HNC) can cause serious speech disorders that can lead to partial or complete loss of speech intel-ligibility in some patients. The clinician's evaluation of the intelligibility level before or after surgical treatment and / or during the rehabilitation phase is an important part of the clinical assessment. Perceptive assessment is the most widely used method in clinical practice to assess the level of intelligibility of a patient despite the limitations associated with it such as subjectivity and moderate reproducibility. In this paper, we propose to overcome these limitations by associating a specific task of speech production based on pseudo-words with an automatic speech processing system, both oriented towards acoustic-phonetic decoding. Compared to human perception, the automatic system reaches very high correlation rates and promising results when applied to a French speech corpus including 41 healthy speakers and 85 patients suffering from HNC

Measuring what matters in healthcare: A practical guide to psychometric principles and instrument development

The provision of quality healthcare relies on scales and measures with robust evidence of their psychometric properties. Using measurement instruments with poor reliability, validity, or feasibility, or those that are not appropriate for the target diagnostic group or construct/dimension under consideration, may be unfavorable for patients, unproductive, and hinder empirical advancement. Resources from the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) group can assist in identifying and developing psychometrically sound measures. The COSMIN initiative is the only international, research-based practice taxonomy and methodological guidelines for measurement in healthcare. This manuscript aims to provide an accessible introduction to theories, principles and practices of psychometrics, instrument properties, and scale development, with applied examples from the COSMIN recommendations. It describes why measurement in healthcare is critical to good practice, explains the concepts of the latent variable and hypothetical construct and their importance in healthcare assessments, explores issues of flawed measurement and briefly explains key theories relevant to psychometrics. The paper also outlines a ten-step process to develop and validate a new measurement instrument, with examples drawn from a recently developed visuoperceptual measure for analysis of disordered swallowing to demonstrate key concepts and provides a guide for understanding properties of and terminology related to measurement instruments. This manuscript serves as a resource for healthcare clinicians, educators, and researchers who seek to develop and validate new measurement instruments or improve the properties of existing ones. It highlights the importance of using psychometrically sound measurement instruments to ensure high-quality healthcare assessments

Primary Structure Revision and Active Site Mapping of E. Coli Isoleucyl-tRNA Synthetase by Means of Maldi Mass Spectrometry

The correct amino acid sequence of E. coli isoleucyl-tRNA synthetase (IleRS) was established by means of peptide mapping by MALDI mass spectrometry, using a set of four endoproteases (trypsin, LysC, AspN and GluC). Thereafter, the active site of IleRS was mapped by affinity labeling with reactive analogs of the substrates. For the ATP binding site, the affinity labeling reagent was pyridoxal 5'-diphospho-5'-adenosine (ADP-PL), whereas periodate-oxidized tRNAIle, the 2',3'-dialdehyde derivative of tRNAIle was used to label the binding site for the 3'-end of tRNA on the synthetase. Incubation of either reagent with IleRS resulted in a rapid loss of both the tRNAIle aminoacylation and isoleucinedependent isotopic ATP-PPi exchange activities. The stoichiometries of IleRS labeling by ADP-PL or tRNAIleox corresponded to 1 mol of reagent incorporated per mol of enzyme. Altogether, the oxidized 3'-end of tRNAIle and the pyridoxal moiety of the ATP analog ADP-PL react with the lysyl residues 601 and 604 of the consensus sequence 601KMSKS605. Identification of the binding site for L-isoleucine or for non cognate amino acids on E. coli IleRS was achieved by qualitative comparative labeling of the synthetase with bromomethyl ketone derivatives of L-isoleucine (IBMK) or of the non-cognate amino acids valine (VBMK), phenylalanine (FBMK) and norleucine (NleBMK). Labeling of the enzyme with IBMK resulted in a complete loss of isoleucine-dependent isotopic [32P]PPi-ATP exchange activity. VBMK, NleBMK and FBMK were also capable of abolishing the activity of IleRS, FBMK being the less efficient in inactivating the synthetase. Analysis by MALDI mass spectrometry designated cysteines-462 and -718 as the target residues of the substrate analog IBMK on E. coli IleRS, whereas VBMK, NleBMK and FBMK labeled in common His-394, His-478 and Cys-718. In addition, VBMK and NleBMK, which are chemically similar to IBMK, were found covalently bound to Cys-462, and VBMK was specifically attached to His-332 (or His-337) of the synthetase. The amino acid residues labeled by the substrate analogs are mainly distributed between three regions in the primary structure of E. coli IleRS: these are segments [325-394], [451-479] and [591-604]. In the 3-D structures of IleRS from T. thermophilus and S. aureus, the [325-394] stretch is part of the editing domain, while fragments [451-479] and [591-604] representing the isoleucine binding domain and the dinucleotide (or Rossmann) fold domain, respectively, are located in the catalytic core. His-332 of E. coli IleRS, that is strictly conserved among all the available IleRS sequences is located in the editing active site of the synthetase. It is proposed that His-332 of E. coli IleRS participates directly in hydrolysis, or helps to deprotonate the hydroxyl group of threonine at the hydrolytic site

Quels tests d'intelligibilité pour évaluer les troubles de production de la parole ?

International audienceSpeech intelligibility is defined as the precision with which a message is understood by an auditor. The loss of intelligibility is often a major complaint for patients with speech production disorders, since it contributes to reducing the quality of life. Several tools currently exist to assess intelligibility but none fully satisfies the clinical constraints. In a first study, we adapted to French language the Frenchay Dysarthria Assessment version 2, a well-known test for English speakers used for evaluating dysarthric speakers. We created the French corpus of words using criteria defined in the FDA -2 and then we tested the protocol over fifty speakers. The results are satisfactory but various methodological bias have led us to continue our efforts in proposing non sense words, which is equivalent to acoustic- phonetic decoding.L'intelligibilité de la parole se définit comme le degré de précision avec lequel un message est compris par un auditeur. A ce titre, la perte d'intelligibilité représente souvent une plainte importante pour les patients atteints de troubles de production de la parole, puisqu'elle participe à la diminution de la qualité de vie au niveau communicationnel. Plusieurs outils existent actuellement pour évaluer l'intelligibilité mais aucun ne satisfait pleinement les contraintes cliniques. Dans une première étude, nous avons adapté au français la version 2 du Frenchay Dysarthria Assessment, un test reconnu dans le milieu anglo-saxon pour l'évaluation de locuteurs dysarthriques. Nous avons créé le corpus de mots français en nous appuyant sur les critères définis dans le FDA-2 puis nous avons testé le protocole sur une cinquantaine de locuteurs. Les résultats sont satisfaisants mais divers biais méthodologiques nous ont conduits à poursuivre notre démarche en proposant des listes de pseudo-mots apparentant le test à du décodage acoustico-phonétique

Impact du trouble de la production de la parole sur les actes communicationnels de la vie quotidienne dans les cancers de la cavité buccale et de l'oropharynx

Cette recherche s'inscrit dans le champ de l'étude de l'impact des actes thérapeutiques sur la qualité de vie des patients. En cancérologie, la mesure de la qualité de vie est globale et ne permet pas de prendre en compte de façon spécifique les facteurs qui contribuent à son amélioration ou son altération. Dans le cadre des cancers de la cavité buccale et de l'oropharynx, qui touchent les structures en jeu dans l'articulation de la parole, un indice automatique de sévérité de la parole a été développé (score C2SI). Comme pour les scores issus de mesures perceptives, il n'est que faiblement corrélé aux scores de questionnaires de qualité vie génériques, et moyennement corrélé aux questionnaires de qualité de vie relatifs à la parole. Ce manque de corrélation nécessite de s'intéresser à l'étape intermédiaire entre sévérité du trouble de parole et qualité de vie, à savoir l'impact fonctionnel du déficit sur la communication des patients. Le retentissement sur les activités de communication du patient dépendra d'une part du niveau de complexité requis par la situation de communication (expression des besoins primaires ou d'un discours argumentatif, expression contextualisée permettant une meilleure prédictibilité de la parole attendue par les interlocuteurs), et d'autre part des besoins de communication selon les cercles sociaux du sujet (et de sa familiarité avec ses interlocuteurs). La prise en compte des facteurs associés (tels que les déficits associés, l'anxiété, la dépression ou l'état cognitif) permettra d'ajuster la mesure du profil de communication de ces patients. L'objectif est ainsi d'étudier si un score objectif de trouble de parole, obtenu par un traitement automatique du signal de parole, permet la détermination de profils d'impact fonctionnel sur la communication des patients traités pour un cancer de la cavité buccale ou de l'oropharynx. Cela pourrait permettre à terme de déterminer des seuils de niveau de sévérité de trouble de la parole selon l'impact fonctionnel sur les actes de communication, comme ce qui existe actuellement en audiométrie (niveaux de surdité selon leur impact fonctionnel pour les sujets). De plus, le développement d'outils objectifs innovants prenant en compte le handicap de communication permettra une amélioration des pratiques cliniques courantes, par une personnalisation de la prise en charge des patients, plus proche de leurs besoins fonctionnels quotidiens

Using Classical Test Theory to Determine the Psychometric Properties of the Deglutition Handicap Index

The Deglutition Handicap Index (DHI) is a self-report measure for patients at risk of oropharyngeal dysphagia on deglutition-related aspects of functional health status (FHS) and health-related quality of life (HR-QoL). The DHI consists of 30 items which are subsumed within the Symptom, Functional and Emotional subscales. The purpose of this study was to evaluate the psychometric properties of the DHI using Classic Test Theory according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. A total of 453 patients with dysphagia with different aetiologies were recruited concurrently at two academic hospitals. Dysphagia was confirmed by fiberoptic endoscopic and/or videofluoroscopic evaluation of swallowing. In addition, a healthy control group of 132 participants were recruited. Structural validity was determined using exploratory and confirmatory factor analyses and internal consistency by calculating Cronbach’s alpha coefficients. Hypothesis testing was evaluated using Mann–Whitney U-tests, linear regression analysis and correlations analysis. Diagnostic performance and receiver operating characteristic curves analysis were calculated. Factor analyses indicated that the DHI is a unidimensional measure. The DHI has good internal consistency with some indication of item redundancy, weak to moderate structural validity and strong hypothesis testing for construct validity. The DHI shows high diagnostic performance as part of criterion validity. These findings support that the DHI is an appropriate choice as a patient self-report measure to evaluate FHS and HR-QoL in dysphagia. Ongoing validation to assess the measure for possible item redundancy and to examine the dimensionality of the DHI using item response theory is recommended

Génération de la « banane de la parole » en vue d'une évaluation objective de l'intelligibilité

L'aire du triangle vocalique, construit en mesurant les valeurs fréquentielles des deux premiers formants des voyelles prononcées, est l'une des mesures employées pour l'évaluation de l'intelligibilité de la parole [1,2]. Le placement des voyelles sur un graphique à deux axes, F1 et F2, permet d'interpréter les valeurs obtenues par rapport au triangle « standard ». Toutefois, les consonnes ont une importance cruciale dans l'intelligibilité de la parole. Stevens et Blumstein [3] affirmaient déjà en 1978 que le lieu d'articulation des consonnes occlusives serait identifiable par l'aspect global de leur représentation spectrale. En audiométrie, la « banane de la parole » est la représentation de la composante fréquentielle principale « standard » de chaque consonne, ainsi que de son intensité, permettant la délimitation d'une aire sur un audiogramme. Cette démarche a été réalisée pour les consonnes de l'anglais [4,5] et du Thaï [6]. Pour le français, Béchet et al. [7] ont calculé des aires consonantiques sur les occlusives sonores [b,d,g], représentant les trois lieux d'articulation les plus communs à l'échelle universelle [8], à l'aide des F2 et F3. Ainsi, nous avons tenté de construire la banane de la parole sur la base des 16 consonnes principales du français. Deux sujets sains (1 homme, 1 femme) ont produit ces 16 consonnes entourées des voyelles « extrêmes » [a,i,u] et des voyelles plus neutres [oe,ø], à trois reprises. En nous inspirant des travaux de Klangpornkun [6], nous avons employé le codage prédictif linéaire (LPC) pour identifier les pics spectraux proéminents des consonnes [9,10] dans les différents contextes vocaliques, et selon le genre du locuteur. En positionnant ces consonnes sur un graphique à deux axes - fréquence et intensité, nous avons ensuite généré la banane de la parole des consonnes du français. Notons qu'au vu de la variabilité interindividuelle des données acoustiques [11,12,13,14], le nombre de sujets dans cette étude préliminaire est limité. De nouveaux enregistrements dans des conditions standardisées sont en cours, visant à obtenir des extraits de parole d'au moins 2 hommes et 2 femmes des tranches d'âge 20-29, 30-39, 40-49, 50-59, 60-69 et 70+. Par l'automatisation de la construction d'une telle représentation des consonnes produites par le sujet, nous espérons pouvoir proposer un outil d'évaluation objective de l'intelligibilité de la parole