Introduction :La prévalence de l’obésité, parmi les patients hospitalisés, est en augmentation. Les patients obèses présentent un risque accru de développer des infections nosocomiales par rapport aux individus non-obèses. Parmi les antibiotiques, la classe des β-lactames est la plus utilisée à l’hôpital tant en prophylaxie chirurgicale que pour le traitement des infections. Les recommandations de doses en vigueur sont basées sur des études pharmacocinétiques (PK) effectuées chez des patients non-obèses. Cependant, les patients obèses présentent des altérations physiologiques qui pourraient théoriquement être à l’origine de modifications des paramètres PK de ces antibiotiques. L’utilisation de doses standards d’antibiotiques pourrait avoir comme conséquence des concentrations sériques inadéquates chez ces patients; elles peuvent, dès lors, conduire à des échecs thérapeutiques et/ou favoriser l’émergence de souches résistantes. Objectifs: Ce travail de thèse a pour but d’approfondir les connaissances sur la PK des β-lactames chez les patients obèses présentant des scores de sévérité clinique différents. Patients et Méthodes: Quatre études PK ont été réalisées chez les patients obèses :1) une étude prospective de patients obèses, et non-obèses, ayant reçu de la céfazoline (CFZ) en prophylaxie de chirurgie digestive, 2) une étude préliminaire, prospective incluant uniquement des patients obèses traités pour des infections non sévères par l’un des 4 β-lactames à large spectre (pipéracilline-tazobactam (TZP), ceftazidime/céfépime (CEF), et méropénem (MEM)), 3) une étude prospective, avec groupe contrôle de patients non-obèses, étudiant la PK du TZP donné en traitement d’infections non sévères et 4) une étude rétrospective cas-témoin évaluant la PK de 4 β-lactames à large spectre (TZP, CEF, ou MEM) donnés pour le traitement d’infections sévères aux soins intensifs. Les taux sériques de ces antibiotiques ont été mesurés par chromatographie liquide et corrélés à plusieurs paramètres démographiques, biologiques et hémodynamiques. Résultats: Etude sur CFZ :Soixante-trois patients ont participé à l’étude: parmi ceux-ci, 43 avaient un index de masse corporelle (IMC) ≥ 35 kg/m2, et 22 un poids total ≥ 120 kg. Sur l’ensemble des patients, les concentrations sériques de CFZ étaient adéquates chez 100% des patients à 180 minutes (T180) et chez 64% (40/63) à 240 minutes (T240) après le début de l’infusion de CFZ. Il n’y avait pas de différence significative entre le pourcentage des patients avec des taux sériques adéquats à T240, quel que soit le paramètre utilisé pour la comparaison (IMC ≥ 35 kg/m2 versus IMC < 35 kg/m2, ou poids total ≥ 120 kg versus poids total < 120 kg). Etude préliminaire sur TZP, CEF et MEM: Cinquante-six patients obèses ont été inclus dans l’étude ;14 ont reçu du MEM, 31 du TZP et 11 du CEF. Parmi ces patients, les concentrations sériques adéquates pour traiter une infection à P. aeruginosa ont été atteintes chez 93% des patients traités par MEM, 68% des patients traités par TZP, et 73% des patients traités par CEF. Le volume de distribution (VD) et la clearance totale (CL) des β-lactames étaient augmentés par rapport à des valeurs rapportées dans la littérature chez les patients non-obèses. En effet, plus de 25% des patients présentaient une clearance en créatinine (CrCl) mesurée supérieure à 150 ml/minute, ce facteur étant identifié comme facteur de risque de concentrations sériques insuffisantes. Etude sur TZP: Trente-deux patients (14 non-obèses et 18 obèses) ont été inclus dans l’étude et ont reçu les doses standards de TZP. Une augmentation du VD (25.4 ± 5.6L vs. 21.0 ± 3.9 L, p= 0.018) et de la CL (18.1 ± 4.7 vs. 13.5 ± 40.1, p= 0.007) a été observé chez les patients obèses par rapport aux non-obèses conduisant à des concentrations statistiquement inférieures de TZP libre par rapport aux patients non-obèses. De même, malgré des valeurs de créatinine sérique semblables (0.8 ± 0.3 versus 0.9 ± 0.3 mg/dl, p=0.26), la CrCl mesurée sur des urines de 24h, était significativement plus élévée chez les obèses par rapport aux non-obèses (128 ± 58 vs. 79 ± 26 ml/min, p=0.006). Etude rétrospective cas-témoin sur TZP, CEF, et MEM aux soins intensifs: Quarante-neuf patients obèses et 59 patients non-obèses ont été inclus. Soixante-huit monitoring thérapeutiques ont été effectués chez les patients obèses et comparés à 68 monitoring thérapeutiques effectués chez les patients non-obèses. Après administration des doses standards des β-lactames, 1/3 des patients obèses avait des concentrations sériques insuffisantes pour traiter des infections à P. aeruginosa, et 1/4 de ces patients avait des concentrations sériques excessives, potentiellement toxiques. Par contre, aucune différence statistiquement significative n’a été observée entre les concentrations sériques des β-lactames des patients obèses et non-obèses. Conclusions :Lors de la prophylaxie chirurgicale, l’administration des doses standards de CFZ a montré des concentrations sériques insuffisantes pour assurer une couverture prophylactique adéquate en cas d’intervention chirugicale d’une durée supérieure à 180 minutes. Ni le poids total, ni l’IMC n’a pu identifier les patients qui nécessiteront une dose plus élevée de CFZ. De même, les doses standards des β-lactames à large spectre se sont avérées insuffisantes dans le traitement des infections non sévères et sévères dues à P. aeruginosa chez les patients obèses. En cas d’infections peu sévères, les concentrations sériques, chez ces patients, étaient significativement moindres que chez les patients non-obèses ;ceci étant lié à une augmentation du VD et de la CL des β-lactames. Un facteur de risque majeur retrouvé était une CrCl augmentée chez les patients obèses. Chez les patients avec infections sévères, la PK des β-lactames n’était par contre pas significativement différente entre les patients obèses et non-obèses. Ceci probablement à cause des perturbations déjà importantes de la PK des β-lactames liées à la séverité du sepsis. En conclusion, ces études identifient des perturbations de la PK des β-lactames chez les patients obèses. Parmi celles-ci, l’augmentation de la clearance rénale est un élement déterminant dans l’inadéquation des concentrations sériques. La situation est plus complexe chez les patients obèses aux soins intensifs où d’autres facteurs peuvent encore s’associer et perturber la PK des β-lactames. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Background: Surgical site infections are the second most common healthcare-related infection and implies high costs for the healthcare. It causes suffering for the patient and places high demands on the nursing care. The nurse's preoperative preparation of the patient is an important part where the patient's possible risk factors should be identified. It is also important that the patient receives information that is suitable for the patient's needs of nursing care. The nurse carries the primary liability of nursing care and has a responsibility to prevent surgical site infections from occurring. Aim: The aim of this study was to investigate the nurse's prerequisites to prevent the occurrence of surgical site infections in hospital care. Method: The chosen method was a literature review based on ten articles of qualitative and quantitative methods published between 2013–2022. Results: The analysis resulted in the following themes and sub-themes:Necessary communication with the sub-themes Team collaboration and Information transfer.Availability of principles and resources with the sub-themes Access to evidence-based guidelines, Pre-, intra- and post-operative premises and knowledge, A safe environment andAccess to materials. Pedagogical ability with the sub-themes Meeting the patient individually and Adequate patient education. Conclusion: The results showed that there were both positive and negative aspects regarding the nurse's prerequisites for preventing surgical site infections, but the negative aspects were overrepresented. The nurses often had the required knowledge but did not use their abilities tothe same extent during work. This resulted in limited nursing care with insufficient complianceto the evidence-based guidelines.

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Minimally Invasive Surgery (MIS) is a growing field including both laparoscopic androbotic operations. Surgeons and engineers are making continual efforts to reduce the negative effects of procedures on patients. Reducing the size of the surgical instruments is one effective method pursued in this effort. When the instruments approach 3 mm in diameter, they reach a threshold where the entry incisions can be small enough that no scar is left on the patient. Laparoscopic instruments on this scale exist but typically lack wrist articulation and only have 1 degree of freedom (DoF). Alternatively, robotic surgical instruments can achieve high levels of dexterity but at a greater diameter. Smaller diameter robotic instruments employ snake wrists but this results in large swept volumes. There is a need for smaller robotic instruments with 3 DoF that preserve a small operational volume. Several unique challenges result when trying to develop small-scale instruments. Friction forces due to the relative motion of actuation cables and other parts in the mechanisms become more significant, as do the challenges of producing and assembling parts with extremely small features. These challenges have been limiting factors for the size of instruments. Traditional mechanisms use pin joints and pulleys which result in higher part counts and higher internal friction. To overcome these challenges, two alternative designs that reduce part count and minimize friction are presented as potential mechanisms that could be used as surgical instruments on the mesoscale (1-5 mm). Both designs implement rolling contact and gearing in place of pin joints and pulleys to realize their motion. Additionally, alternative manufacturing methods that are ideally suited to mesoscale production are presented. Micro metal laser sintering and composite carbon nanotude structures are shown to have the resolution required to create the detailed features necessary for these new designs. The result are two mechanisms suited to be produced as mesoscale, robotically actuated, surgical instruments. One of the two designs has been physically prototyped and has demonstrated clinical capabilities at 4 and 5 mm diameter instrument sizes.

<p> Osteoarthritis (OA) is the most common arthritis, and the second most common diagnosis leading to disability. While loss of joint function is disabling, patients report that the greatest disabler of OA is the pain. Unfortunately, OA pain remains an unmet medical need. Numerous mechanisms have been proposed for the pathogenesis of OA pain. However, none of these mechanisms has led to satisfactory evidence-based treatment for OA pain. There is a critical need to address the mechanisms for OA pain due to the aging demographics and the prevalence of OA in older adults. This thesis project was aimed to study neural mechanisms for OA pain. The general hypothesis was that the pain of OA arises as a result of phenotypic changes in primary sensory neurons, especially in larger diameter A-fiber neurons. In vivo intracellular recordings were used to determine changes in specific populations of DRG neuron in a surgical knee derangement model of OA in the rat. It was found that AB-fiber low threshold mechanoreceptors, particularly muscle spindle afferents underwent significant changes (including changes in action potential configurations and in responses to repetitive stimulation) one month following the model induction when histopathological changes of the knee joint and the nocifensive behaviors of the affected lower limb favor OA. Nociceptors, including C-, As- and AB-fiber neurons remained largely unchanged at one month OA. AB-fiber high threshold mechanoreceptors exhibited significant changes at two month OA, a later phase during the progression of OA. The data demonstrate that distinct populations of dorsal root ganglia neuron are altered during the progression of OA, which might be the neuronal basis for clinical presentations of sensory deficit in OA including pain and loss of proprioception. The data also suggest that the pain in OA might be a form of neuropathic pain. </p> / Thesis / Doctor of Philosophy (PhD)

To understand pain processing requires the assessment of an individual’s perception of pain with temporal stimulation over different periods. Offset analgesia (OA), a phenomenon widely studied, refers to a disproportionate decrease in pain experience following a small reduction in temperature during noxious thermal stimulation. OA leads to skin desensitization, causing brief pain inhibition at the stimulation site and leading to adaptation and a decrease in pain scores. To avoid sensitization and habituation during thermal pain procedures, previous studies have utilized protocols in which the thermal stimulation is applied to different areas of the skin (e.g., upper forearm versus lower forearm). The reliability of this thermal pain calibration procedure in producing a nonadaptive effect has been previously tested using pain rating scales. The utilization of neuroimaging to further elucidate these relationships has not been widely studied, but it is likely an important tool to investigate these constructs. Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical imaging technique that measures changes in hemoglobin (Hb) concentrations within the brain using the characteristic absorption spectra of Hb in the near-infrared range. This thesis investigated whether adaptation exists across four conditions of the OA paradigm using fNIRS. Introducing fNIRS to define significant differences in brain metrics (e.g., activated regions of interest) in participants who have undergone surgery and are experiencing chronic pain as well as healthy, pain-free controls could have implications for more accurate measures of OA and more reliable pain treatment options. In this study, noxious thermal stimulation was given to 19 participants on the forearm of the nondominant hand through a commonly used three-temperature OA paradigm with offset, constant, and control trials. Each OA paradigm consisted of four conditions (A, B, C, and D) with a pseudorandom sequence design of three trials. OA was implemented with the participant while real-time fNIRS data were obtained on the subject’s prefrontal and somatosensory cortices, regions known to be involved in pain processing. Hemoglobin responses during the four OA trials were evaluated and compared within experimental conditions. Repeated measures ANOVA was used to analyze the significant differences among conditions. Results showed no significant differences among the four OA trials. The findings of this thesis study indicated that brain response from the prefrontal and somatosensory cortices is not affected within the four OA trials. The consistent brain activation across multiple trials of stimulation suggests an absence of adaptive responses. In line with previous findings, these results imply the reliability of such thermal pain calibration procedures by fNIRS brain imaging. Further investigation with a larger sample size is likely for the verification of the findings from this study. / 2026-02-14T00:00:00Z

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