Palpation force modulation strategies to identify hard regions in soft tissue organs

This work was supported by EPSRC MOTION grant (grant number EP/N03211X/1), National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and Vattikuti Foundation

Robotic simulators for tissue examination training with multimodal sensory feedback

Tissue examination by hand remains an essential technique in clinical practice. The effective application depends on skills in sensorimotor coordination, mainly involving haptic, visual, and auditory feedback. The skills clinicians have to learn can be as subtle as regulating finger pressure with breathing, choosing palpation action, monitoring involuntary facial and vocal expressions in response to palpation, and using pain expressions both as a source of information and as a constraint on physical examination. Patient simulators can provide a safe learning platform to novice physicians before trying real patients. This paper reviews state-of-the-art medical simulators for the training for the first time with a consideration of providing multimodal feedback to learn as many manual examination techniques as possible. The study summarizes current advances in tissue examination training devices simulating different medical conditions and providing different types of feedback modalities. Opportunities with the development of pain expression, tissue modeling, actuation, and sensing are also analyzed to support the future design of effective tissue examination simulators

Recent Advances in Robot-Assisted Surgery: Soft Tissue Contact Identification

Robot-Assisted Minimally Invasive Surgery (RAMIS) is becoming standard-of-care in western medicine. RAMIS offers better patient outcome compared to traditional open surgery, however, the surgeons’ ability to identify the tissues with the sense of touch is missing from most robotic systems. Regarding haptic feedback, the most promising diagnostic technique is probably palpation; a physical contact examination method through which information can be gathered about the underlying structures by gently pressing with the fingers. In open surgery, palpation is widely used to identify blood vessels, tendons or even tumors; and the knowledge on the exact location of such elements is often crucial with respect to the outcome of the intervention. This paper presents a review of the actual research directions in the field of palpation in RAMIS

Development and psychometric validation of pain scales in feline osteoarthritis

L’arthrose féline est détectable sur radiographie, surtout chez l’animal âgé. La rareté antérieure du diagnostic clinique s’explique par ses signes subtils et facilement attribués à d’autres maladies gériatriques ou au processus normal de vieillissement. Ces signes répondent néanmoins au traitement analgésique. Le but de ce projet de recherche était de développer et valider deux grilles de douleur arthrosique (Montreal Instruments for Cat Arthritis Testing), une pour les propriétaires de chats [MI-CAT(C)], et une pour les vétérinaires [MI-CAT(V)]. Le développement était fondé sur une revue de la littérature, notre expertise clinique en douleur et en comportement félin, et un sondage de propriétaires de chats arthrosiques. Des experts internes et externes ont confirmé la validité de contenu des grilles. Ensuite, une étude pilote sur chats de laboratoire a permis une évaluation préliminaire de leur fiabilité et validité. Dans le cadre d’un essai clinique chez des chats arthrosiques, la grille pour propriétaires MI-CAT(C) discriminait les groupes placebo et meloxicam, et ses changements de score corrélaient avec l’activité motrice et l’âge, soutenant sa validité. La grille était généralement facile à comprendre, appuyant de façon préliminaire sa validité de face (l’acceptabilité) et son interprétation. La mesure de fiabilité intra- et inter-observateur préconisait l’évaluation par le propriétaire principal vs. un(e) propriétaire secondaire. La grille MI-CAT(C) était homogène, sans redondance, selon l’évaluation préliminaire de la consistance interne. Une seconde évaluation de la grille vétérinaire MI-CAT(V) a été menée chez des chats de laboratoire (avec ou sans arthrose naturelle). L’évaluation de la fiabilité intra- et inter-observateur démontrait une courbe d’apprentissage pour le nouvel utilisateur de la grille. Seules les sous-catégories Gait (démarche) et Posture (allure) avaient une tendance (non-significative) à détecter le statut arthrosique; la palpation et la manipulation des articulations n’avait aucune sensibilité du même genre. Gait et Posture corrélaient avec une mesure objective, la force verticale d’appui au sol. Une analyse vidéo a ensuite été faite pour améliorer la sensibilité de la grille MI-CAT(V) à l’arthrose. La grille révisée a été soumise à des étapes successives de validation et de raffinement, via trois études thérapeutiques (utilisant la gabapentine, le tramadol, et le meloxicam sous forme orale transmuqueuse par vaporisateur). Sa fiabilité intra- et inter-observateur, et l’évaluation préliminaire de la consistance interne étaient bonnes à excellentes, et elle fut capable de détecter le statut arthrosique. Cependant, elle ne détecta pas les effets thérapeutiques démontrés par d’autres mesures objectives. Des recherches ultérieures devront confirmer que la grille pour propriétaires MI-CAT(C) distingue le statut arthrosique, et évaluer sa réponse, vs. placébo, à d’autres traitements que le meloxicam. La grille vétérinaire MI-CAT(V) requerra une confirmation de sa fiabilité et validité chez des chats de propriétaires ; elle nécessitera encore des raffinements pour détecter les effets de traitement. L’établissement de seuils (p. ex. : distinction arthrosique/non-arthrosique, différence minimale significative) pour les deux grilles est conseillé pour faciliter leur utilisation clinique, ainsi qu’une évaluation de leur faisabilité et utilité clinique, ainsi qu’une réévaluation de leur structure interne et de leur compréhension.Radiographic signs of osteoarthritis are prevalent in cats, becoming more common with age. Historically, the rate of diagnosis has tended to be low, suggesting that signs are subtle and/or tend to be attributed to normal age-related changes or to other geriatric diseases. However, cats with osteoarthritis display signs that are responsive to analgesic treatment. This project aimed to develop and validate rating scales for detection and measurement of feline osteoarthritis pain and related disability (the Montreal Instruments for Cat Arthritis Testing). Two such scales, one for use by caretakers/owners [MI-CAT(C)], and one for use by veterinarians [MI-CAT(V)], were developed based on a review of the literature, expert opinion, and a survey study of owners of cats with a diagnosis of osteoarthritis. The content validity (via expert review) was excellent for both scales. A pilot study in a colony of laboratory cats with naturally-occurring osteoarthritis evaluated reliability and ability to detect osteoarthritis status, for both scales; preliminary revisions were made based on the results. The MI-CAT(C) owner scale subsequently underwent validation in a clinical trial of meloxicam in client-owned osteoarthritic cats. Evidence for validity included the ability to distinguish placebo from active treatment, and correlations with objectively measured activity and age. Owners found most scale items clear/easy to understand, preliminarily supporting comprehensibility and face validity (acceptability). Evaluation of intra- and inter-rater reliability suggested that secondary owners varied substantially in their ability to complete the scale, compared to primary owners. A preliminary assessment of internal consistency reliability supported homogeneity, without redundancy, of the scale. The MI-CAT(V) veterinary scale was evaluated in a study of laboratory cats with and without naturally-occurring osteoarthritis. Intra- and inter-rater reliability assessments suggested that a naïve user’s ability to use the scale was influenced by experience with it. The scale was unable to distinguish osteoarthritic and non-osteoarthritic cats, but the subcategories Gait and Posture were somewhat promising based on a non-significant tendency to detect osteoarthritis status, and correlations with an objective measure of osteoarthritis pain, peak vertical force. Palpation of the limbs did not detect osteoarthritis status. A video analysis was performed to increase MI-CAT(V) scale sensitivity to osteoarthritis. Subsequent evaluation and refinements based on three therapeutic trials (involving gabapentin, tramadol, and oral transmucosal meloxicam treatments) in laboratory cats with and without naturally-occurring osteoarthritis resulted in good to excellent intra- and inter-rater reliability, and ability to detect osteoarthritis status. Preliminary evidence supported scale internal consistency. Therapeutic response detected by objective outcome measures was not demonstrable using the scale. It is recommended that the MI-CAT(C) owner scale be evaluated for ability to distinguish osteoarthritic from non-osteoarthritic cats. The MI-CAT(V) veterinary scale requires testing in client-owned cats, and potentially further refinements to permit detection of treatment effects, if it is to be used as more than a disease screening tool. Both scales require additional investigation of internal structure and comprehensibility, and determination of cut-points to guide clinical use (e.g., minimally important difference, and thresholds for classification of cats as osteoarthritic vs. non-osteoarthritic), and evaluation of their feasibility and clinical utility

Description, Classification, and Prediction of Dengue Illnesses in a Thai Pediatric Cohort: A Dissertation

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are emerging infectious diseases which are endemic in many regions of the globe, many of which are resource-poor areas. DHF and DF impose a severe economic health burden in tropical and subtropical areas. Dengue virus causes an acute febrile illness that can be a self-limited febrile illness, as seen in most cases of DF, or a life-threatening illness with plasma leakage and shock, as seen in cases of DHF. A systematic review of the literature revealed gaps in the knowledge base of clinical laboratory findings of dengue illness with regards to longitudinal dynamics and classification and predictive modeling of disease severity. The objective of this thesis was to investigate the utility of clinical laboratory variables for classification and prediction of disease outcomes. The data used in this investigation was derived from a prospective study of Thai children presenting to either of two study hospitals within 72 hours of onset of an acute febrile illness. Systematic data collection, including clinical laboratory parameters, and routine clinical management continued each day until 24 hours after the fever had subsided. A final diagnosis of DHF, DF, or other febrile illness (OFI) was assigned by an expert physician after chart review. The first research objective of this study was to describe the temporal dynamics of clinical laboratory parameters among subjects with DHF, DF, or OFI. Data were analyzed using lowess curves and population-average models. Quadratic functions of clinical variables over time were established and demonstrated significantly divergent patterns between the various diagnostic groups. The second research objective was to establish and validate tools for classification of illness severity using easily obtained clinical laboratory measures. Bivariate logistic regression models were established using data from one hospital in an urban area of Thailand as a training data set and validated with a second data set from a hospital in a rural area of Thailand. The validated models maintained a high sensitivity and specificity in distinguishing severe dengue illnesses without using the hallmark indicators of plasma leakage. The third research objective used classification and regression tree (CART) analysis to established diagnostic decisions trees using data obtained on the day of study enrollment, within the first 3 days of acute illness. Decision trees with high sensitivity were established for severe dengue defined either as: 1) DHF with evidence of shock (dengue shock syndrome, DSS); or 2) DSS or dengue with significant pleural effusion. This study expands existing knowledge of the potential utility of clinical laboratory variables during different phases of dengue illness. The application of the results of these studies should lead to promising opportunities in the fields of epidemiological research and disease surveillance to reduce the health burden, and improve the clinical management, of dengue illness. Future directions involve application of these algorithms to different study populations and age groups. Additionally, other analytical techniques, such as those involving CART analysis, can be explored with these data

Uterine contractions clustering based on surface electromyography: an input for pregnancy monitoring

Tese de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, em 2018Inicialmente a investigação da contratilidade uterina recorria à utilização de dois métodos: o tocograma externo e o cateter de pressão intrauterino. Ambos os métodos apresentam limitações ao nível da avaliação do risco de parto prematuro e na monitorização da gravidez. O EHG (Electrohisterograma) é um método alternativo ao tocograma externo e ao cateter de pressão intrauterino. Este método pode ser aplicado de forma invasiva no músculo uterino, ou de forma não invasiva através de elétrodos colocados no abdómen. O EHG tem sido considerado uma ferramenta adequada para a monitorização da gravidez e do parto. O índice de massa corporal tem um impacto quase impercetível no EHG, sendo esta uma das principais características deste método. O EHG pode também ser utilizado para identificar as mulheres que vão entrar em trabalho de parto e ainda auxiliar na tomada de decisão médica quanto à utilização da terapia tocolítica (antagonista da oxitocina), evitando deste modo a ingestão de medicação desnecessária e os consequentes efeitos secundários. Na literatura existem apenas cinco casos publicados em que foi realizada uma separação dos principais eventos do sinal EHG: contrações, movimentos fetais, ondas Alvarez e ondas LDBF (Longue Durée Basse Fréquence). Em três das publicações a separação dos eventos foi feita manualmente e nos restantes casos algoritmos, como redes neuronais, foram aplicados ao EHG. As ondas Alvarez e as Braxton-Hicks são as mais reconhecidas. As ondas Alvarez foram descritas pela primeira vez nos anos cinquenta e as Braxton-Hicks foram descritas pela primeira vez em 1872 sendo detetadas através de palpação. As ondas Alvarez são ocasionalmente sentidas pela mulher. Estas ondas estão localizadas numa pequena área do tecido uterino sem propagação e podem levar a contrações com maior intensidade e, consequentemente, ao parto pré-termo. As Braxton-Hicks são contrações ineficientes registadas a partir da 20ª semana de gravidez que se tornam mais frequentes e intensas com o decorrer da gravidez. Estas contrações são menos localizadas que as ondas Alvarez e, durante o parto, propagam-se por todo o tecido uterino num curto período de tempo. As Braxton-Hicks estão associadas a uma diminuição do ritmo cardíaco fetal. As ondas LDBF são contrações de longa duração associadas a hipertonia uterina, quando há contração do tecido uterino sem retorno ao relaxamento muscular, o que representa um risco na gravidez. Neste trabalho foram utilizadas duas bases de dados. Na base de dados da Islândia existem 122 registos de 45 mulheres, dos quais apenas 4 correspondem a partos pré-termo. Na base de dados TPEHG (Term-Preterm EHG) existem 300 registos, dos quais 38 correspondem a partos pré-termo. Neste trabalho foram escolhidos canais bipolares, visto que estes reduzem o ruído idêntico, como o ECG (Eletrocardiograma) materno ou movimentos respiratórios. Para ambas as bases de dados os sinais originais de EHG foram processados e filtrados. Na estimação espetral foram considerados dois métodos: paramétricos e não paramétricos. O método Welch foi escolhido pois representa um bom compromisso entre ambos. Este método foi utilizado para calcular o espectro de cada evento detetado no sinal EHG. Para detetar os eventos no sinal EHG foram considerados cinco métodos baseados na energia ou amplitude. O método Wavelet foi o escolhido pois após uma inspeção visual, este era o método que delineava melhor as contrações. Na base de dados da Islândia foram identificadas 3136 contrações e na TPEHG foram encontradas 4622 contrações. O objetivo principal desta tese é obter clusters de contrações detetadas no sinal EHG. No entanto, as contrações são séries temporais não estacionárias, e a sua classificação visual é inviável a longo termo e também difícil de aplicar na prática clínica. Existem vários parâmetros que podem ser extraídos do sinal EHG, mas o espectro das contrações foi o método escolhido visto que este representa o sinal EHG e tem sempre a mesma dimensão, independentemente da duração da contração. As distâncias espetrais têm sido utilizadas com sucesso no reconhecimento áudio. Neste trabalho foi realizada uma aplicação desse método ao processamento do EHG, no qual foram realizados os ajustes necessários. Para comparar os espectros foram estudadas 8 distâncias diferentes: Itakura-Saito, COSH, Itakura, Itakura simétrica, Kullback-Leibler, Jeffrey, Rényi e Jensen-Rényi. Apenas as distâncias simétricas foram selecionadas para um estudo mais detalhado visto que estas são, segundo a literatura, as distâncias mais adequadas aquando do clustering. Após comparação das distâncias simétricas, a divergência de Jeffrey foi a selecionada para a comparação dos espectros. Nesta tese foram avaliados três métodos diferentes de clustering: o linkage, o K-means e o K-medoids. O linkage é um método hierárquico. Os clusters que resultam do agrupamento hierárquico estão organizados numa estrutura chamada dendrograma. No agrupamento hierárquico, não é necessário predeterminar o número de clusters, o que torna este um método ideal na exploração dos dados. O K-means e o K-medoids são métodos de partição, nos quais os dados são separados em k clusters decididos previamente. Os clusters são definidos de forma a otimizar a função da distância. No algoritmo K-means, os clusters baseiam-se na proximidade entre si de acordo com uma distância predeterminada. A diferença entre o K-medoids e o K-means é que o K-medoids escolhe pontos de dados como centros, chamados de medoides, enquanto K-means usa centróides. Após uma comparação dos diferentes métodos de clustering foi escolhido neste trabalho foi o average linkage, visto que este apresentava melhores resultados quer na separação dos espectros quer na silhueta. É então apresentado um método inovador no qual se utiliza todo o espectro das contrações detetadas automaticamente no EHG para o clustering não supervisionado. Esta técnica é uma contribuição para a classificação automática das diferentes contrações, especialmente aquelas mais reconhecidas na literatura: Alvarez e Braxton-Hicks. Era expectável encontrar um cluster isolado com as ondas LDBF, visto que estas representam um risco para o feto. O principal objetivo era juntar num cluster os espectros semelhantes das contrações, e relacioná-lo com o respetivo tipo de contração. Essa tarefa foi concluída através da identificação positiva de Alvarez e Braxton-Hicks. O clustering forneceu ainda algumas pistas sobre ondas Alvarez que não foram encontradas com o algoritmo de deteção de contrações, situação para a qual um método alternativo é apresentado. É sugerido que as ondas Alvarez sejam detetadas com métodos baseados na frequência, como, por exemplo, a frequência instantânea, no entanto este método não foi desenvolvido neste trabalho. Em relação às ondas LDBF, estas foram encontradas no cluster das Braxton-Hicks. É sugerido que a deteção das ondas LDBF seja baseada na sua caraterística mais distinta: a longa duração. Verificou-se que os casos pré-termo e os registos pré-parto não ficaram isolados num cluster, não se tendo encontrado uma relação entre a idade gestacional e o tipo de contração. Conclui-se que as contrações mais curtas apresentam maior amplitude do que as contrações com maior duração. Baseado em estudos anteriores sobre a eletrofisiologia do útero, supõem-se que o início do trabalho de parto pré-termo e termo esteja associado a sequências específicas de diferentes tipos de contrações, nas quais as ondas Alvares desempenham um papel importante. As contrações identificadas como Alvarez e Braxton-Hicks não são usadas como tal na prática clínica apesar de a maioria das contrações detetadas pelo tocograma serem Braxton-Hicks. O interesse pelas ondas Alvarez diminuiu rapidamente visto que estas ondas são praticamente indetetáveis pelo método de referência de deteção de contrações: o tocograma. As capacidades e a resolução do EHG levaram à renovação do estudo das contrações mais subtis, incluindo as Alvarez. Este trabalho é uma contribuição para a investigação nesta área.An innovative technique is introduced wherein where an unsupervised clustering method using as feature the whole spectrum of automatically detected contractions on the EHG (Electrohysterogram) is presented as a contribution to the automatic classification of the different uterine contractions, at least those that have been most recognized in the literature: Alvarez and Braxton-Hicks. It was expected to also be able to cluster the LDBF (Longue Durée Basse Fréquence) components, as these pose a fetal risk. The main task was to have the spectral contractions descriptions clustered and linked to the respective contraction type. That task was completed with positive identification of the Alvarez and Braxton-Hicks. The clustering process also provided clues regarding the missed Alvarez waves in the contraction detection algorithm, for which an alternative technique is suggested but not developed in this work. Regarding the LDBF they were found in the Braxton-Hicks cluster. It is suggested the LDBF´s to be detected based in their most prominent feature: the long duration. It is presented the rationale behind the selection of a cost function to be used in the spectral distance’s algorithm. Spectral distances have been successfully used in audio recognition and this works represents an application to the EHG processing, for which the necessary adjustments have to be implemented. It was found that no single cluster pointed to the preterm cases, or indeed to the pre-labor subject recordings. It is hypothesized, based on previous studies in uterine electrophysiology, that the initiation of pre-term or term labor should be associated with triggering contraction sequences of different types, where the Alvarez waves play a major role. Alvarez and Braxton-Hicks, labeled as such, are not typically used in the clinical environment despite most of the Tocogram detected contractions being the latter. Alvarez waves are not usually detectable by the Tocogram. Alvarez were firstly detected invasively in the early fifties, and Braxton-Hicks in 1872 using routine palpation techniques. The interest in Alvarez components declined rapidly since being practically undetectable by the de facto reference in the contraction detection: the Tocogram. The EHG capabilities and resolution made it possible to revive the research on the most subtle uterine contractions, Alvarez included and this work is a contribution in this research area

Development and evaluation of a haptic framework supporting telerehabilitation robotics and group interaction

Telerehabilitation robotics has grown remarkably in the past few years. It can provide intensive training to people with special needs remotely while facilitating therapists to observe the whole process. Telerehabilitation robotics is a promising solution supporting routine care which can help to transform face-to-face and one-on-one treatment sessions that require not only intensive human resource but are also restricted to some specialised care centres to treatments that are technology-based (less human involvement) and easy to access remotely from anywhere. However, there are some limitations such as network latency, jitter, and delay of the internet that can affect negatively user experience and quality of the treatment session. Moreover, the lack of social interaction since all treatments are performed over the internet can reduce motivation of the patients. As a result, these limitations are making it very difficult to deliver an efficient recovery plan. This thesis developed and evaluated a new framework designed to facilitate telerehabilitation robotics. The framework integrates multiple cutting-edge technologies to generate playful activities that involve group interaction with binaural audio, visual, and haptic feedback with robot interaction in a variety of environments. The research questions asked were: 1) Can activity mediated by technology motivate and influence the behaviour of users, so that they engage in the activity and sustain a good level of motivation? 2) Will working as a group enhance users’ motivation and interaction? 3) Can we transfer real life activity involving group interaction to virtual domain and deliver it reliably via the internet? There were three goals in this work: first was to compare people’s behaviours and motivations while doing the task in a group and on their own; second was to determine whether group interaction in virtual and reala environments was different from each other in terms of performance, engagement and strategy to complete the task; finally was to test out the effectiveness of the framework based on the benchmarks generated from socially assistive robotics literature. Three studies have been conducted to achieve the first goal, two with healthy participants and one with seven autistic children. The first study observed how people react in a challenging group task while the other two studies compared group and individual interactions. The results obtained from these studies showed that the group interactions were more enjoyable than individual interactions and most likely had more positive effects in terms of user behaviours. This suggests that the group interaction approach has the potential to motivate individuals to make more movements and be more active and could be applied in the future for more serious therapy. Another study has been conducted to measure group interaction’s performance in virtual and real environments and pointed out which aspect influences users’ strategy for dealing with the task. The results from this study helped to form a better understanding to predict a user’s behaviour in a collaborative task. A simulation has been run to compare the results generated from the predictor and the real data. It has shown that, with an appropriate training method, the predictor can perform very well. This thesis has demonstrated the feasibility of group interaction via the internet using robotic technology which could be beneficial for people who require social interaction (e.g. stroke patients and autistic children) in their treatments without regular visits to the clinical centres

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not

Epidemiological studies of inflammatory airway disease in horses

Studies of respiratory disease in different populations of horses were undertaken, including a case control study, using clinically apparent respiratory disease in Thoroughbred racehorses as the case definition. Controls were matched on date and training yard and data were analysed using conditional logistic regression. Disease was statistically associated with several infectious and non-infectious risk factors. Younger horses, those entering training within the last 3 months and those with Actinobacillus/Pasteurella spp. or Mycoplasma felis isolated from the trachea were at increased risk of clinical disease. When all controls with sub-clinical disease were excluded, tracheal Streptococcus zooepidemicus infection was significantly associated with disease. An experimental bacterial vaccine against S. zooepidemicus and Actinobacillus spp. was evaluated for its effect on natural respiratory disease in Welsh Mountain pony foals using a blinded, randomised, controlled trial. Weekly examinations were conducted in 29 ponies, of which 12 received vaccine, 12 received placebo and 5 were untreated. Data were analysed using a multilevel modeling approach, with autoregressive variables to adjust for significant effects of disease in previous time periods. Tracheal infection with S. zooepidemicus was a significant risk factor for aggregated clinical scores and clinical signs of nasal discharge, cough and dyspnoea. There was evidence for a significant dose response between S. zooepidemicus infection and dyspnoea and inflammatory airway disease. Both pony-level and observation-level analyses demonstrated significant variation in clinical scores between ponies with transferrin haplotypes D or F2. Tracheal and nasopharyngeal isolates of S. zooepidemicus from the ponies in the vaccination study were typed by polymerase chain reaction of the hypervariable region of the M-protein (5 possible types) and the 16S-23S RNA gene intergenic spacer (8 possible types). More S. zooepidemicus types were isolated from the trachea than the nasopharynx. There was evidence for clonal succession of types over time and novel S. zooepidemicus types were identified. There were apparent differences in the strength of association of different S. zooepidemicus types with respiratory disease in these ponies during the study period

Characterization of oral pain in cats after dental extractions in a multidisciplinary approach

Les maladies bucco-dentaires sont fréquemment rapportées en médecine vétérinaire et le traitement généralement nécessite l’extraction des dents. Cependant, la procédure est invasive et une évaluation à long terme ainsi qu’une gestion de la douleur sont nécessaires. En médecine vétérinaire, les opioïdes, les blocs anesthésiques locaux et les anti-inflammatoires non stéroïdiens sont administrés en intervention analgésique péri-opératoire. Par exemple, la buprénorphine est un opioïde analgésique puissant, hautement lipophile, et est principalement utilisé pour traiter la douleur aiguë. La buprénorphine est souvent administrée dans le cadre d'une analgésie multimodale. Les signes comportementaux de la douleur induite par les maladies bucco-dentaires n'ont pas été systématiquement étudiés chez les chats, et les connaissances actuelles sont principalement basées sur des preuves anecdotiques ou des études réalisées chez d'autres espèces. On ignore comment les maladies bucco-dentaires et le traitement (c'est-à-dire l'extraction dentaire) peuvent affecter la prise alimentaire péri-opératoire, les scores de douleur, les besoins analgésiques supplémentaires et les comportements chez les chats. En outre, il serait important de savoir si l’échelle de douleur basée sur l'expression faciale (Feline Grimace Scale: FGS) pourrait également être utilisée pour l'évaluation de la douleur buccale. Les objectifs du projet étaient 1) d'identifier les comportements spécifiques associés aux maladies bucco-dentaires en utilisant une évaluation par vidéo, et de les corréler aux scores de la douleur en temps réel, 2) d'évaluer l'impact des maladies bucco-dentaires et de la douleur sur la prise alimentaire et les comportements liés à l'alimentation, 3) de déterminer les effets du traitement des maladies bucco-dentaires sur le comportement, les scores de la douleur et la prise alimentaire, 4) d’évaluer la fiabilité inter-évaluateurs du FGS et 5) pour évaluer l'efficacité analgésique et les événements indésirables d'une formulation à haute concentration de formulation de chlorhydrate de buprénorphine (Simbadol, 1,8 mg / mL) en comparaison avec une formulation standard de chlorhydrate de buprénorphine (Vetergesic, 0,3 mg / mL) dans le cadre d'un schéma multimodal chez les chats subissant des extractions dentaires. Les hypothèses étaient que 1) des comportements spécifiques pourraient être identifiés et corrélés aux scores de la douleur en temps réel, 2) les chats atteints d'une maladie bucco-dentaire sévère auraient une consommation alimentaire plus faible et des scores de douleur plus élevés et nécessiteraient une analgésie de secours comparativement aux chats qui ne sont pas / minimalement atteints par une maladie bucco-dentaire, 3) le traitement des maladies bucco-dentaires réduirait la prévalence des comportements spécifiques ainsi que les scores de douleur et améliorerait la consommation alimentaire de ces animaux, 4) les scores FGS notés par différents évaluateurs seraient fiables et 5) Simbadol et Vetergesic produiraient tous deux des scores de douleur postopératoire, des événements indésirables, ainsi que le moment et la prévalence de l'analgésie de secours similaires lors de l'utilisation du Glasgow Composite Measure Pain Scale-Feline (CMPS-F). Le projet a été divisé en deux études et quatre articles (étude 1: articles 1 à 3, étude 2: article 4): 1) article sur le score de la douleur, les besoins en analgésie de secours et la quantité de nourriture ingérée chez les chats subissant un traitement oral, 2) article sur les comportements spécifiques induits par la douleur liés à la douleur buccale chez les chats sous traitement oral, 3) article sur la fiabilité inter-évaluateurs de la FGS chez les chats sous traitement oral, et 4) comparaison détaillée de l'efficacité analgésique de deux schémas posologiques en utilisant deux concentrations différentes de buprénorphine chez les chats subissant des extractions dentaires. Dans le premier article, vingt-quatre chats ont été répartis également en deux groupes: un groupe qui représente des maladies bucco-dentaires légères (traitement dentaire minimal) et un autre sévères (extractions dentaires multiples) sur la base d'un système de notation dentaire qui impliquait le nombre et l'emplacement de l'extraction des dents et hospitalisés pendant 7 jours (admission au jour 0, examen bucco-dentaire, radiographies et traitement sous anesthésie générale le jour 1 et sortie le jour 6). Pendant l'hospitalisation, les scores de douleur basés sur l'échelle composite de Glasgow (CMPS-F), la prévalence de l'analgésie de secours (CMPS-F ≥ 5/20), la prise d'aliments secs et mous (%) pendant 3 minutes et 2 heures, l'apport quotidien d'aliments mous et les cytokines inflammatoires sériques ont été analysés. Dans le deuxième article, les chats ont été filmés à distance pendant 10 min tout au long de l'étude à différents moments (au total 36h d'enregistrement vidéo). Les vidéos se composaient de quatre parties soit les comportements généraux, de jeu, d'alimentation et post-alimentation. La durée et la fréquence des différents comportements basés sur un éthogramme ont été analysées. Dans le troixième article, quatre-vingt-onze captures d'images (c'est-à-dire des captures d'écran) à partir de vidéos filmées aux jours 1 (postopératoire 6 heures) et 6 pour l'article 2 et des vidéos filmées avant / après l'analgésie de sauvetage ont été incluses. Le FGS comprend cinq unités d'action (AU): les yeux, les oreilles, le museau, les moustaches et la position de la tête. Les scores FGS des images ont été évalués indépendamment par quatre évaluateurs en aveugle. La fiabilité inter-évaluateurs de chaque score AU et FGS total et l'effet de la présence du soignant ont été évalués. Dans l'étude 2 (article 4), vingt-trois chats subissant des extractions dentaires ont été inclus. Les chats ont reçu aléatoirement soit Simbadol (1.8 mg/mL; 0.24 mg/kg SC, toutes les 24 heures, n = 11) ou Vetergesic (0.3 mg/mL; 0.02 mg/kg IM, toutes les 8 h, n = 12) tout au long de l'étude. Ils ont été admis au jour 0, ont subi un examen oral, des radiographies et un traitement sous anesthésie générale le jour 1 et ont été libérés le jour 4. La sédation et la douleur ont été évaluées à l'aide de l'échelle visuelle analogique interactive dynamique (jour 1) et CMPS-F, respectivement. Les scores de sédation, de douleur et la prévalence de l'analgésie de secours (CMPS-F ≥ 5/20) et du ressentiment (défini comme tout type de comportement d'évitement associé à l'aversion pour l'administration de médicaments) ont été analysés statistiquement. Les études ont montré que les scores de la douleur et la prévalence de l'analgésie de secours étaient significativement élevés, ainsi que les apports d'aliments secs et mous étaient significativement diminués chez les chats atteints d'une maladie grave par rapport à ceux présentant une maladie légère. De surcroit, la maladie buccale influence les cytokines inflammatoires et induit des comportements. Par ailleurs, Le FGS est un outil fiable pour l’évaluation de la douleur buccale et n’est pas affecté par la présence du soignant. En outre, les scores de la douleur et la prévalence de l'analgésie de secours chez les chats auxquels Simbadol a été administré n'étaient pas significativement différents de ceux administrés par Vetergesic. De plus, certains chats administrés par Vetergesic ont développé un ressentiment à l'égard de l'administration du médicament, qui n'était pas significativement différent de ceux administrés par Simbadol. Une analgésie à long terme est nécessaire après des extractions dentaires chez les chats atteints d'une maladie bucco-dentaire sévère. La diminution de l'apport alimentaire et les comportements spécifiques identifiés dans les études pourraient être utilisés pour différencier entre les chats douloureux des chats indolores dans la pratique clinique. Le FGS est un outil fiable pour l'évaluation de la douleur chez les chats subissant des extractions dentaires. Simbadol a produit des effets analgésiques similaires à Vetergesic sans induire un ressentiment pendant l'administration du médicament.Oral disease is one of the most commonly reported diseases in veterinary medicine, and tooth extractions are commonly required as the treatment. The procedure, however, is invasive, and long-term pain management is necessary. In veterinary medicine, opioids, local anesthetic blocks and nonsteroidal anti-inflammatory drugs are administered as perioperative analgesic intervention. Behavioral signs of oral disease-induced pain have not been systematically investigated in cats, and the current knowledge is mostly based on anecdotal evidence or studies performed in other species. It is not known how oral disease and the treatment (i.e. tooth extractions) can affect perioperative food intake, pain scores, additional analgesic requirements and behaviors in cats. Also, it is not known if a facial expression-based pain scale (Feline Grimace Scale: FGS) could be used for oral pain assessment as well. The objectives of this PhD program were: 1) to identify the specific behaviors associated with oral disease by using video assessment, and to verify their correlation with the real-time pain scores, 2) to assess the impact of oral disease and pain on food intake and feeding-related behaviors, 3) to determine the effects of oral disease treatment on behavior, pain scores and food intake, 4) to assess the inter-rater reliability of the FGS in cats undergoing dental extractions and 5) to evaluate the analgesic efficacy and adverse events of a high-concentration formulation of buprenorphine hydrochloride formulation (Simbadol, 1.8 mg/mL) in comparison with a standard buprenorphine hydrochloride formulation (Vetergesic, 0.3 mg/mL) as part of a multimodal regimen in cats undergoing dental extractions. The hypotheses were: 1) specific behaviors associated with oral disease would be identified and correlated with real-time pain scores, 2) cats with severe oral disease would have lower food intake and higher pain scores, and require rescue analgesia when compared with cats with no/minimal oral disease, 3) treatment of oral disease would reduce the prevalence of specific behaviors and pain scores and improve food consumption of these animals, 4) the FGS scores scored by different raters would be reliable in cats undergoing dental extractions and 5) both Simbadol and Vetergesic would produce similar postoperative pain scores, adverse events and timing and prevalence of rescue analgesia when using the Glasgow Composite Measure Pain Scale-Feline (CMPS-F). The project was divided into two studies and four articles (study 1: articles 1-3, study 2: article 4): 1) investigation of pain scores, rescue analgesia requirements and the amount of food intake in cats undergoing oral treatment, 2) investigation of the pain-induced specific behaviors related to oral pain in cats undergoing oral treatment, 3) investigation of inter-rater reliability of FGS in cats undergoing oral treatment, and 4) comparison of the analgesic efficacy of two dosage regimens using two different concentrations of buprenorphine in cats undergoing dental extractions. In article 1, twenty-four cats were equally divided into minimal (minimal dental treatment) or severe (multiple dental extractions) oral disease groups based on a dental scoring system which involved the number and location of teeth extraction and hospitalized for 7 days (admission on day 0, oral examination, radiographs and treatment under general anesthesia on day 1 and discharge on day 6). During hospitalization, pain scores based on CMPS-F, the prevalence of rescue analgesia (CMPS-F ≥ 5/20), dry and soft food intake (%) during periods of 3 minutes and 2 hours, daily soft food intake and serum inflammatory cytokines were analyzed and compared. In article 2, cats were filmed remotely for 10 min throughout the study at different time points (total of 36h of video recording). The videos consisted of four parts namely general, playing, feeding and post-feeding behaviors. The duration and frequency of different behaviors based on an ethogram were analyzed. In article 3, ninety-one image captures (i.e. screenshots) from videos filmed at days 1 (postoperative 6 hours) and 6 for article 2 and videos filmed before/after rescue analgesia were included. The FGS comprises five action units (AU): eyes, ears, muzzle, whiskers and head position. The FGS scores of the images were independently scored by four blinded raters. Inter-rater reliability of each AU and total FGS scores and the effect of the caregiver’s presence were evaluated. In study 2 (article 4), twenty-three cats undergoing tooth extractions were included. Cats randomly received either Simbadol (1.8 mg/mL; 0.24 mg/kg SC, every 24h, n = 11) or Vetergesic (0.3 mg/mL; 0.02 mg/kg IM, every 8h, n = 12) throughout the study. They were admitted on day 0, underwent oral examination, radiographs and treatment under general anesthesia on day 1 and discharged on day 4. Sedation and pain were scored using the dynamic interactive visual analog scale (day 1) and CMPS-F¬, respectively. Sedation and pain scores and the prevalence of rescue analgesia (CMPS-F ≥ 5/20) and resentment (defined as any type of escape behavior associated with aversion to drug administration) were analyzed. The studies found that the pain scores and the prevalence of rescue analgesia were significantly increased, and dry and soft food intakes were significantly decreased in cats with severe disease when compared with those with minimal disease, and the oral disease influences inflammatory cytokines and induces the specific behaviors. FGS is a reliable tool for the assessment of oral pain and is not affected by the caregiver’s presence. Pain scores and the prevalence of rescue analgesia in cats administered Simbadol were not significantly different from those administered Vetergesic, and some cats administered Vetergesic developed resentment to the administration of the drug, which was not significantly different from those administered Simbadol. Long-term analgesia is required after dental extractions in cats with severe oral disease. A decrease in food intake and specific behaviors identified in the studies could be used to differentiate painful versus pain-free cats in clinical practice. The FGS is a reliable tool for pain assessment in cats undergoing dental extractions. Simbadol produced similar analgesic effects to Vetergesic without resentment during drug administration