La construction sociale et l’hybridation des logiques marchandes et du système de santé dans l’émergence, le succès et la pérennité des entreprises de technologies innovantes en santé

Avec l’avènement de la micro-informatique dans les années 80, de l’internet dans les années 90 et de l’achèvement du séquençage du génome humain au tournant du 21e siècle, le nombre d’entreprises développant des technologies en santé a explosé. Par contre, la pratique en centre hospitalier et des interactions quotidiennes avec des professionnels de la santé œuvrant dans différents secteurs du système de santé québécois et d’autres provinces canadiennes rend compte d’une large différence entre le nombre de technologies qui apparaissent dans les conférences et blogs, et celles adoptées et utilisées sur le terrain. Mais tandis que l’évaluation des technologies et l’étude de la diffusion des innovations ont donné lieu à une littérature scientifique importante, peu d’études ont exploré jusqu’à présent l’émergence des entreprises de technologies innovantes en santé en prenant compte le point de vue de tous les acteurs impliqués. C’est donc ce manque de connaissances que notre étude désire combler, en se demandant comment une entreprise émergente et de technologie en santé peut se construire socialement en initiant certaines actions concurrentielles et pourquoi ces actions peuvent-elles différer selon le type d’entreprise, les demandes et les pressions des acteurs économiques et du système de santé. Les objectifs de recherche sont donc de définir comment les entreprises innovatrices en technologie de la santé s'établissent en utilisant l'effet de leurs actions concurrentielles tout en leur octroyant un sens, déterminer l'influence du type d'entreprise et des schèmes de construction sociale sur les actions concurrentielles, les activités de fabrication de sens et les réponses aux pressions des acteurs institutionnels, et enfin identifier quelles sont les stratégies utilisées par les entrepreneurs pour s'adresser à l'institution qu’est le système de santé. Afin de répondre aux interrogations soulevées par les observations sur le terrain, la présente recherche s’est organisée en trois volets successifs, explorant trois points de vue différents. Le premier est celui d’un observateur externe envers les startups en technologie de santé. Le deuxième volet est celui des acteurs gravitant autour de ces entreprises et le troisième est celui des entrepreneurs eux-mêmes. Le premier volet consiste en une étude de cas multiples utilisant la stratégie d’analyse de construction d’explication. L'étude s'est appuyée sur l'analyse des communiqués de presse (n = 664) et des articles des médias généraux (n = 627). L'échantillon comprend cinq entreprises canadiennes inscrites à la Bourse de Toronto sous la forme de quatre startups qui ont fait une offre d’achat initiale entre 2000 et 2003, et une entreprise bien établie. Parmi celles-ci, trois étaient dans le secteur de la santé, une dans le secteur du commerce électronique tandis que l‘entreprise bien établie était une entreprise de solutions d’infrastructures électroniques en santé. Globalement, au cours de l'émergence de l'entreprise, les actions marketing et symboliques, doublées du recours à des leaders d’opinion et des personnes de haute notoriété ont été nettement plus prononcées avec les startups de santé par rapport à l'entreprise qui n’était pas en santé. Au cours des premiers mois d’émergence, au fur et à mesure que les communications et signaux augmentaient, les startups en santé étaient les seules entreprises à utiliser la légitimité cognitive et pragmatique, s'appuyant ainsi sur la cognition plutôt que sur l'intérêt personnel ou les jugements moraux des acteurs. De plus, nous avons observé des différences dans l'utilisation des actions marketing et des actions symboliques et également dans le recours à des leaders d’opinion. Cela suggère une influence différentielle du modèle de construction sociale et du type d'entreprise sur le niveau et le mélange des actions du marché et des activités de sensibilisation entre les entreprises de santé et les entreprises de technologie non liées à la santé. Les deuxième et troisième volet consistent en deux séries d’entrevues semi-structurées, où une analyse thématique a été utilisée pour identifier et rapporter des thèmes tout en organisant et en décrivant minutieusement l'ensemble de données. Pour le deuxième volet, l'échantillon pour les entrevues semi-structurées comprend 10 médecins spécialistes, 4 professionnels de la santé impliqués dans l'acquisition des technologies de la santé, 3 membres des unités d'évaluation des technologies de la santé et 3 investisseurs en technologies de la santé. Nous avons déterminé que l'acquisition et la diffusion des technologies de santé sont de plus en plus réglementées et doivent répondre à des pressions croissantes d'un grand nombre d'acteurs qui voient inversement leur pouvoir d'agence se réduire. Nous avons également démontré que les pressions qui pousse vers l'institutionnalisation des pratiques, ainsi que le découplage des objectifs du système de santé et ceux des autres acteurs sont abordés par des stratégies "politiques"; le pouvoir des principaux influenceurs tels que les investisseurs et les spécialistes médicaux, ainsi que la méfiance à l'égard des actions de marketing sont abordés avec des stratégies “associatives”; les pressions découlant du besoin croissant de données fondées sur des données probantes sont traitées avec des stratégies “normatives”. Enfin, la faible fragmentation d'un système public de santé et l'hétérogénéité des processus d'acquisition locaux sont abordées avec des stratégies “d'identité”. Le troisième volet s’est concentré sur la manière dont les entrepreneurs saisissent les opportunités, créent leur organisation entrepreneuriale, et lui apportent de la légitimité, et a examiné les déclencheurs, contraintes et pressions impliquées dans ce processus. L'échantillon pour les entretiens a été constitué de 20 entrepreneurs et partenaires stratégiques impliqués dans le développement et la commercialisation des technologies de la santé. À chaque étape, nous avons identifié un processus institutionnel prédominant, qu'il s'agisse du découplage, de l'influence du champ organisationnel ou de la recherche de légitimation. Nous avons constaté que chaque étape de l'émergence de la start-up était déclenchée par des situations où l'entrepreneur faisait face à des barrières et contraintes sous la forme d'un désalignement des limites, de la mauvaise performance des technologies concurrentes, et de l'asymétrie des ressources. Nos résultats peuvent aider les professionnels de la santé, les décideurs et les évaluateurs à comprendre le processus d'adoption et de diffusion des technologies en santé et contribuer à l'élaboration de procédures d'acquisition grâce à des politiques ciblées et des processus révisés. Pour les investisseurs, notre étude leur permet d’identifier les obstacles qui rythment la vitesse à laquelle les nouvelles technologies font leur chemin dans la pratique clinique et le système de santé. Les résultats peuvent aussi fournir un cadre pour élaborer des données de référence pour évaluer les investissements actuels et futurs. Mieux connaître quelles sont les différences propres aux startups technologiques en santé en comparaison aux autres startups pourrait aider les entrepreneurs à prioriser les actions compétitives et à mieux cerner les intentions perçues et les besoins de santé réels lors de l’émergence sociale de l’entreprise. Pour le système de santé, les résultats peuvent servir à élaborer et enrichir des politiques et directives d’acquisition et d’évaluation qui vont améliorer l’accès à des technologies médicales qui sont sécuritaires, efficaces et de haute qualité.With the advent of micro-computing in the 1980s, the Internet in the 1990s and the completion of the sequencing of the human genome at the turn of the 21st century, the number of companies developing health technologies has exploded. Nonetheless, hospital practice and day-to-day interactions with health professionals working in different sectors of the Quebec health system and other Canadian provinces reflect a large difference between the number of technologies appearing in conferences and blogs, and those adopted and used in the field. But while the evaluation of technologies and the study of the diffusion of innovations led to an important scientific literature, few studies have so far explored the emergence of innovative health technology companies taking into account the point of view of all the actors involved. It is this lack of knowledge that our study wishes to fill, by asking how an emerging health technology company can be socially constructed by initiating certain competitive actions and why these actions may differ according to the type of company, demands and pressures from economic and healthcare system actors. The research objectives are therefore to define how innovative health technology companies establish themselves by using the effect of their competitive actions while giving them meaning, determining the influence of the type of business and the patterns of social construction activities on competitive actions, sensemaking activities and responses to the pressures of institutional actors, and finally identify the strategies used by entrepreneurs to address the institution that is the health system. In order to answer the questions raised by field observations, this research was organized in three successive parts, exploring three different points of view. The first is that of an external observer to health technology start-ups. The second part is that of the actors around these companies and the third is that of the entrepreneurs themselves. The first part consists of a multiple case study using explanation-building analysis strategy. The study was based on the analysis of press releases (n = 664) and general media articles (n = 627). The sample includes five Canadian companies listed on the Toronto Stock Exchange in the form of four startups that made an initial bid from 2000 to 2003 and a well-established firm. Of these, three were in the health sector, one in the e-commerce sector, while the well-established company was a health electronic infrastructure solutions company. Overall, during the emergence of the company, marketing and symbolic actions, coupled with the use of opinion leaders and high-profile people, were significantly more pronounced with the health-based startups when compared to the firm who was not in the health sector. In the early months of emergence, as communications and signals increased, health-based startups were the only firms to use cognitive and pragmatic legitimacy, relying on cognition rather than personal interest or moral judgment of the actors. In addition, we observed differences in the use of marketing and symbolic actions and also in the use of opinion leaders. This suggests a differential influence of the social construction model and firm type on the level and mix of market actions and sensegiving activities between health and non-health technology companies. The second and third components consist of two sets of semi-structured interviews, where a thematic analysis was used to identify and report themes while organizing and describing the data set thoroughly. For the second part, the sample for semi-structured interviews includes 10 medical specialists, 4 health professionals involved in health technology acquisition, 3 health technology assessment units’ members, and 3 investors in health technologies. We have determined that the acquisition and diffusion of health technologies are increasingly regulated and must respond to increasing pressures from a large number of actors who, conversely, see their agency power diminish. We also found that the pressures to institutionalize practices, as well as the decoupling of the objectives of the health system from those of other actors, are addressed by “political” strategies; the power of key influencers such as investors and medical specialists, as well as mistrust of marketing actions are addressed with “associative” strategies; the pressures arising from the growing need for evidence-based evidence are addressed through “normative” strategies. Finally, the fragmentation of a public health system and the heterogeneity of local procurement processes are approached with “identity” strategies. The third part focuses on how entrepreneurs seize opportunities, create their entrepreneurial organization, and give it legitimacy, and examined the triggers, constraints and pressures involved in this process. The sample for the interviews consisted of 20 entrepreneurs and strategic partners involved in the development and commercialization of health technologies. At each stage, we identified a predominant institutional process, whether it be the decoupling, the influence of the organizational field or the search for legitimation. We found that each stage of the start-up was triggered by situations where the entrepreneur faced barriers and constraints in the form of a misalignment of boundaries, poor performance of competing technologies, and of resource asymmetry. Our findings can help healthcare professionals, decision-makers and evaluators understand the process of adoption and diffusion of health technologies and contribute to the development of procurement procedures through targeted policies and revised processes. For investors, our study allows them to identify the barriers that pace the speed at which new technologies are making their way into clinical practice and the health care system. The results can also provide a framework for developing baseline data to evaluate current and future investments. A better understanding of the differences in health technology startups compared to other startups could help entrepreneurs prioritize competitive actions and better understand perceived intentions and real health needs during the social emergence of the company. For the healthcare system, the results can be used to develop and enrich procurement and evaluation policies and guidelines that will improve access to safe, effective and high quality medical technologies

Les inhibiteurs de pompes à protons comme facteur de risque pour les diarrhées à Clostridium difficile chez des patients de soins intensifs

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

A systematic review of the use of the Satiety Quotient

The satiating efficiency of food has been increasingly quantified using the Satiety Quotient (SQ). The SQ integrates both the energy content of food ingested during a meal and the associated change in appetite sensations. This systematic review examines the available evidence regarding its methodological use and clinical utility. A literature search was conducted in 6 databases considering studies from 1900 to April 2020 that used SQ in adults, adolescents and children. All study designs were included. From the initial 495 references found, 52 were included. Of the studies included, 33 were acute studies (29 in adults and 4 in adolescents) and 19 were longitudinal studies in adults. A high methodological heterogeneity in the application of the SQ was observed between studies. Five main utilizations of the SQ were identified: its association with i) energy intake; ii) anthropometric variables; iii) energy expenditure/physical activity; iv) sleep quality and quantity; as well as v) to classify individuals by their satiety responsiveness (i.e. low and high satiety phenotypes). Altogether, the studies suggest the SQ as an interesting clinical tool regarding the satiety responsiveness to a meal and its changes in responses to weight loss in adults. The SQ might be a reliable clinical indicator in adults when it comes to both obesity prevention and treatment. There is a need for more standardized use of the SQ in addition to further studies to investigate its validity in different contexts and populations, especially among children and adolescents

Wide-field optical spectroscopy system integrating reflectance and spatial frequency domain imaging to measure attenuation-corrected intrinsic tissue fluorescence in radical prostatectomy specimens

The development of a multimodal optical imaging system is presented that integrates endogenous fluorescence and diffuse reflectance spectroscopy with single-wavelength spatial frequency domain imaging (SFDI) and surface profilometry. The system images specimens at visible wavelengths with a spatial resolution of 70 microm, a field of view of 25 cm(2) and a depth of field of approximately 1.5 cm. The results of phantom experiments are presented demonstrating the system retrieves absorption and reduced scattering coefficient maps using SFDI with <6% reconstruction errors. A phase-shifting profilometry technique is implemented and the resulting 3-D surface used to compute a geometric correction ensuring optical properties reconstruction errors are maintained to <6% in curved media with height variations <20 mm. Combining SFDI-computed optical properties with data from diffuse reflectance spectra is shown to correct fluorescence using a model based on light transport in tissue theory. The system is used to image a human prostate, demonstrating its ability to distinguish prostatic tissue (anterior stroma, hyperplasia, peripheral zone) from extra-prostatic tissue (urethra, ejaculatory ducts, peri-prostatic tissue). These techniques could be integrated in robotic-assisted surgical systems to enhance information provided to surgeons and improve procedural accuracy by minimizing the risk of damage to extra-prostatic tissue during radical prostatectomy procedures and eventually detect residual cancer

Identifying conditions for inducible protein production in E. coli: combining a fed-batch and multiple induction approach

BACKGROUND: In the interest of generating large amounts of recombinant protein, inducible systems have been studied to maximize both the growth of the culture and the production of foreign proteins. Even though thermo-inducible systems were developed in the late 1970's, the number of studies that focus on strategies for the implementation at bioreactor scale is limited. In this work, the bacteriophage lambda P(L )promoter is once again investigated as an inducible element but for the production of green fluorescent protein (GFP). Culture temperature, induction point, induction duration and number of inductions were considered as factors to maximize GFP production in a 20-L bioreactor. RESULTS: It was found that cultures carried out at 37°C resulted in a growth-associated production of GFP without the need of an induction at 42°C. Specific production was similar to what was achieved when separating the growth and production phases. Shake flask cultures were used to screen for desirable operating conditions. It was found that multiple inductions increased the production of GFP. Induction decreased the growth rate and substrate yield coefficients; therefore, two time domains (before and after induction) having different kinetic parameters were created to fit a model to the data collected. CONCLUSION: Based on two batch runs and the simulation of culture dynamics, a pre-defined feeding and induction strategy was developed to increase the volumetric yield of a temperature regulated expression system and was successfully implemented in a 20-L bioreactor. An overall cell density of 5.95 g DW l(-1 )was achieved without detriment to the cell specific production of GFP; however, the production of GFP was underestimated in the simulations due to a significant contribution of non-growth associated product formation under limiting nutrient conditions

The Logarithmic Sobolev Constant of The Lamplighter

We give estimates on the logarithmic Sobolev constant of some finite lamplighter graphs in terms of the spectral gap of the underlying base. Also, we give examples of application

Tabletop imaging of structural evolutions in chemical reactions

The introduction of femto-chemistry has made it a primary goal to follow the nuclear and electronic evolution of a molecule in time and space as it undergoes a chemical reaction. Using Coulomb Explosion Imaging we have shot the first high-resolution molecular movie of a to and fro isomerization process in the acetylene cation. So far, this kind of phenomenon could only be observed using VUV light from a Free Electron Laser [Phys. Rev. Lett. 105, 263002 (2010)]. Here we show that 266 nm ultrashort laser pulses are capable of initiating rich dynamics through multiphoton ionization. With our generally applicable tabletop approach that can be used for other small organic molecules, we have investigated two basic chemical reactions simultaneously: proton migration and C=C bond-breaking, triggered by multiphoton ionization. The experimental results are in excellent agreement with the timescales and relaxation pathways predicted by new and definitively quantitative ab initio trajectory simulations

An open vibration platform to evaluate postural control using a simple reinforcement learning agent

In this paper, our research team proposes an inexpensive open vibration platform built from easily available electronic components to be used as a tool by physiotherapists in order to help them in their evaluation of the postural control of individuals at risk of postural imbalance which could lead to falls. The platform has been thought to be easily reproducible and all the code necessary to make it work is made available on the researchers’ websites. In addition, a simple reinforcement learning agent has been developed and tested to automatically calibrate the vibration motors for optimal stimulation. Finally, we present in this paper pilot experiments done on 7 healthy participants (40.8 years old) to validate the proper functioning of the platform

The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis

Objectives Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice