Les transfusions sanguines sont fréquemment employées pour corriger l’anémie secondaire à une arthroplastie de la hanche ou du genou. Il n’y a cependant pas consensus sur les indications de transfuser. La tendance actuelle est d’utiliser une stratégie transfusionnelle restrictive (soit un seuil de 75-80 g/L d’hémoglobine) mais les conséquences d’une telle pratique sur la récupération fonctionnelle et la qualité de vie des patients sont mal connues. Dans un premier temps, nous avons caractérisé la pratique transfusionnelle au Centre hospitalier de l’Université de Montréal (CHUM). Notre hypothèse était que, devant l’imprécision des recommandations, la pratique transfusionnelle serait variable. Une étude rétrospective de 701 dossiers de patients ayant subi une arthroplastie de la hanche ou du genou a été réalisée. Nous avons observé que les transfusions étaient utilisées de la même façon dans les trois hôpitaux et que les médecins basaient leur décision de transfuser principalement sur un seul chiffre, la concentration d’hémoglobine, adoptant une stratégie restrictive. Soixante-six pourcent des patients avaient une concentration d’hémoglobine inférieure à 100 g/L au départ de l’hôpital. Dans un deuxième temps, nous avons évalué l’impact de cette anémie postopératoire sur la récupération fonctionnelle et la qualité de vie des patients. Notre hypothèse était qu’il existe une concentration d’hémoglobine en dessous de laquelle celles-ci sont atteintes. Une étude de cohorte prospective et observationnelle a été menée chez 305 patients regroupés selon leur concentration d’hémoglobine postopératoire. Les groupes d’hémoglobine (≤ 80, 81-90, 91-100 et > 100 g/L) étaient similaires dans l’évolution de la distance de marche en six minutes, de l’évaluation de l’effort fourni, de la force de préhension et des scores de qualité de vie. L’anémie modérée n’est donc pas associée à une atteinte de la récupération fonctionnelle et de la qualité de vie à court terme. D’autres études devront déterminer les conséquences à long terme d’une stratégie transfusionnelle restrictive sur ces patients. / Red blood cell transfusions are frequently used to treat anemia after total hip or knee arthroplasties. The indications for transfusions remain unclear despite published guidelines. Clinicians have adopted a restrictive transfusion threshold (75-80 g/L) but the consequences of such a strategy on functional outcome and quality of life are not known. First, we characterized the transfusion practice inside the Centre hospitalier de l’Université de Montréal (CHUM). Our hypothesis was that transfusion practice varies inside the CHUM due to uncertainty. A retrospective study of 701 charts of patients operated for a hip or knee arthroplasty was conducted. We observed that there was no difference among hospitals regarding the way transfusions are used and that physicians mainly based their decision to transfuse on a single variable, the hemoglobin concentration, adopting a restrictive transfusion strategy. Sixty-six percent of patients had a hemoglobin concentration under 100 g/L after surgery. Second, we evaluated the impact of this postoperative anemia on functional outcome and quality of life. We hypothesized that a threshold hemoglobin concentration exists below which these become impaired. A prospective, observational cohort study was conducted in 305 patients categorized in groups according to their postoperative hemoglobin concentration. Hemoglobin groups (≤ 80, 81-90, 91-100 and > 100 g/L) were similar in the evolution of the distance walked in six minutes, perception of effort, maximal dominant hand strength and quality of life scores. Thus, moderate anemia is not associated with an impaired functional recovery or quality of life early after hip and knee arthroplasties. Further studies will be required to determine the long-term consequences of a restrictive transfusion strategy in these patients.

Introduction & Objectifs : Pour assurer l’analgésie postopératoire, l’anesthésiste dispose, en plus des différentes classes de médicaments administrés par voie orale ou intraveineuse, de diverses techniques pour bloquer l’influx nerveux douloureux en administrant les anesthésiques locaux (AL) de manière centrale ou périphérique. La ropivacaïne (ROP), un AL à longue durée d’action, est un médicament de première intention partout dans le monde, en raison de sa grande efficacité et de son faible risque de toxicité. Contrairement à certains pays, la ROP n'est toujours pas indiquée au Canada pour la rachianesthésie (bloc central) en raison d'un manque de données probantes. Jusqu'à présent, les efforts de recherche ont essentiellement porté sur la sécurité ainsi que sur la durée d’action du médicament lorsqu’administré par voie spinale. De plus, les doses optimales de ROP pour l’anesthésie régionale périphérique ne sont pas encore précisément connues. La posologie devrait être adaptée au site d’administration ainsi qu’à l’intensité et la durée du stimulus produit par la chirurgie. Ultimement, cela permettrait aux cliniciens d’identifier le régime optimal en fonction des facteurs démographiques qui pourraient affecter la pharmacocinétique (PK) et la pharmacodynamie (PD) de l’AL (objectif global de ces travaux). Validation de la Méthode Analytique Manuscrit 1 : Une méthode analytique spécifique et sensible permettant de déterminer les concentrations plasmatiques de ROP a d’abord été optimisée et validée. Validation du Biomarqueur Manuscrit 2 : Nous avons ensuite mis au point et évalué la fiabilité d’une méthode quantitative basée sur la mesure du seuil de perception sensorielle (CPT) chez le volontaire sain. Ce test nécessite l’application d’un courant électrique transcutané qui augmente graduellement et qui, selon la fréquence choisie, est capable de stimuler spécifiquement les fibres nerveuses impliquées dans le cheminement de l’influx nerveux douloureux. Les résultats obtenus chez les volontaires sains indiquent que la mesure CPT est fiable, reproductible et permet de suivre l’évolution temporelle du bloc sensitif. Études cliniques Manuscrit 3 : Nous avons ensuite caractérisé, pendant plus de 72 h, l’absorption systémique de la ROP lorsqu’administrée pour un bloc du nerf fémoral chez 19 patients subissant une chirurgie du genou. Le modèle PK populationnel utilisé pour analyser nos résultats comporte une absorption biphasique durant laquelle une fraction de la dose administrée pénètre rapidement (temps d’absorption moyen : 27 min, IC % 19 – 38 min) dans le flux sanguin systémique pendant que l’autre partie, en provenance du site de dépôt, est redistribuée beaucoup plus lentement (demi-vie (T1/2) : 2.6 h, IC % 1.6 – 4.3 h) vers la circulation systémique. Une relation statistiquement significative entre l’âge de nos patients et la redistribution de l’AL suggère que la perméabilité tissulaire est augmentée avec l’âge. Manuscrit 4 : Une analyse PK-PD du comportement sensitif du bloc fémoral (CPT) a été effectuée. Le modèle développé a estimé à 20.2 ± 10.1 mg la quantité de ROP nécessaire au site d’action pour produire 90 % de l’effet maximal (AE90). À 2 X la AE90, le modèle prédit un début d’action de 23.4 ± 12.5 min et une durée de 22.9 ± 5.3 h. Il s’agit de la première étude ayant caractérisé le comportement sensitif d’un bloc nerveux périphérique. Manuscrit 5 : La troisième et dernière étude clinique a été conduite chez les patients qui devaient subir une chirurgie du genou sous rachianesthésie. Tout comme pour le bloc du nerf fémoral, le modèle PK le plus approprié pour nos données suggère que l’absorption systémique de la ROP à partir du liquide céphalo-rachidien est biphasique; c.à.d. une phase initiale (T1/2 : 49 min, IC %: 24 – 77 min) suivie (délai: 18 ± 2 min) d'une phase légèrement plus lente (T1/2 : 66 min, IC %: 36 – 97 min). L’effet maximal a été observé beaucoup plus rapidement, soit aux environs de 12.6 ± 4.9 min, avant de revenir aux valeurs de base 210 ± 55 min suivant l’administration de l’agent. Ces données ont permis d’estimer une AE50 de 7.3 ± 2.3 mg pour l'administration spinale. Conclusion : En somme, ces modèles peuvent être utilisés pour prédire l’évolution temporelle du bloc sensitif de l’anesthésie rachidienne et périphérique (fémorale), et par conséquent, optimiser l’utilisation clinique de la ROP en fonction des besoins des cliniciens, notamment en ce qui a trait à l’âge du patient. / Background & Objectives: To provide postoperative analgesia, the anesthesiologist has at his disposal a panel of different medications and also regional techniques of neural blockade. Loco-regional analgesia (central or peripheral) blocks conduction of painful influx to the central nervous system by the use of local anesthetics (LA). Among these drugs, ropivacaine (ROP), has an enormous potential given is long-acting efficacy and low incidence of toxicity. Currently, ROP is not licensed for use in spinal anesthesia (central block) in all countries due to a lack of data from controlled clinical trials. So far, research efforts on this topic have mainly focused on safety and dose-finding issues. In addition, the most appropriate dose for a peripheral nerve block has never been estimated empirically. Dosing recommendation for LAs should be site-specific and adapted to the intensity of the stimuli produced by a surgery and to the duration of analgesia required. Ultimately, these should guide clinicians in identifying the most appropriate block for the individual patients by taking into account demographic factors that may affect the pharmacokinetics (PK) and pharmacodynamics (PD) of LA overall objective of the current research) Analytical Method Validation Manuscript 1: First, a specific and sensitive assay has been developed and validated for the determination of ROP in human plasma. Biomarker Validation Manuscript 2: Second, the reliability of a neurostimulator measuring current perception threshold (CPT) was assessed in healthy volunteers. The device uses a constant transcutaneous electrical sine wave stimulus at different frequencies specific to pain-conducting fibers. Our results suggest that CPT are reliable and can be applied to characterize, in a quantitative manner, the sensory onset of a peripheral nerve block in a clinical setting. Clinical Studies Manuscript 3: The systemic absorption of ROP after a femoral nerve block in orthopedic patients was then characterized using extended rich PK-sampling, i.e. up to 4 days post-dosing. Our model used for data analysis confirms that, in a similar manner to neuraxial sites of LAs injection, the systemic absorption of ROP from the femoral space is biphasic, i.e. a rapid initial phase (mean absorption time of 25 min, % CI: 19 – 38 min) followed by a much slower phase (half-life (T1/2) of 3.9 h, % CI: 2.9 – 6.0 h). A significant age-related increase in the permeability of the LA was also observed in our elderly patients (n = 19, age = 62.6 ± 7.1 yr). Manuscript 4: A population PK-PD analysis of the sensory anesthesia (CPT) of ROP using our PK model was also performed. The effect-site amount producing 90% of the maximum possible effect (AE90) was estimated as 20.2 ± 10.1 mg. At 2 x AE90, the sigmoid Emax model predicted an onset time of 23.4 ± 12.5 min and a duration of 22.9 ± 5.3 h. To the best of our knowledge, this is the first PK-PD model developed for a peripheral nerve block. Manuscript 5: In the third and last study, a similar approach was used to characterise the PK-PD relationship of intrathecally administered ROP in patients undergoing minor lower limb surgery. The biphasic release of the agent from the intrathecal space was modeled using a rapid initial absorption phase (T1/2 of 49 min, % CI: 24 – 77 min) followed (lag-time of ~ 18 ± 2 min) by a slightly slower input rate (T1/2 of 66 min, % CI: 36 – 97 min). ROP maximal response was observed within 12.6 ± 4.9 min of dosing, with a subsequent return to baseline 210 ± 55 min after the administration of the LA. The effect-site amount producing 50 % of the Emax (AE50) was estimated at 7.3 ± 2.3 mg. Conclusion: Altogether, the proposed models can be used to predict the time-course of sensory blockade after a femoral nerve block and spinal anesthesia using ROP and to optimize dosing regimen according to clinical needs with regard to important cofactors such as age.

Abstrakt Bakgrund: Forskning visar att generell anestesi kan bidra till kognitiv dysfunktion postoperativt. En alltför djup anestesi och/eller en lång duration av anestesi är två faktorer som kan inverka på kognitionen med besvär såsom minnesproblem och koncentrationssvårigheter. Anestesisjuksköterskans roll är att individanpassa anestesin för att inte orsaka för djup anestesi och därmed har det blivit alltmer vanligt att monitorera anestesidjupet för att minska på onödigt lidande för patienten. Syfte: Syftet är att kartlägga anestesidjup och anestesiduration  hos patienter med självskattad  kognitiv svikt efter elektiv ortopedisk operation. Metod: För att kartlägga detta valdes en retrospektiv observationsstudie med tvärsnittsdesign med insamlad data från kvalitetsregister. Resultat: Av 920 patienter var det 116 patienter som uppgav kognitiv dysfunktion dag 1 postoperativt och upp till över 16 dagar postoperativt med  ett genomsnittsvärde på 37,7 i entropy och 104,4 minuter i anestesiduration. Slutsats: Desto längre duration av anestesin och ju djupare anestesi desto mer kognitiv påverkan postoperativt. Anestesidjupsmonitorering bör användas mer frekvent och önskvärt är att bedöma kognition preoperativt med ett mätinstrument för att kunna se om skillnad finns postoperativt.

INTRODUÇÃO: A cifose em pacientes com mielomeningocele representa uma deformidade complexa, cujo tratamento é eminentemente cirúrgico, com altas taxas de complicação. OBJETIVOS: O objetivo deste estudo é relatar os resultados e complicações observados no tratamento da cifose associada à mielomeningocele, assim como avaliar se a intervenção tem algum impacto na qualidade de vida relacionada à saúde desses pacientes. MÉTODO: Este é um estudo prospectivo de série de casos operados em três instituições em São Paulo nos anos de 2012 e 2013. A técnica utilizada foi a que é conhecida como \"de Dunn-McCarthy\", e consiste na cifosectomia e fixação posterior, utilizando-se hastes moldadas em \"S\" através dos forâmens de S1 associadas a parafusos pediculares na coluna torácica. Os resultados foram registrados como ângulo da cifose (pelo método de Cobb) antes e depois da cirurgia, além de tempo de cirurgia e de internação e volume de sangue transfundido. Os pacientes foram todos operados pela mesma equipe de cinco cirurgiões e responderam a dois módulos do questionário de qualidade de vida PedsQL, o módulo principal (questionário genérico, QG) e o módulo neuromuscular (MNM). Todos os eventos adversos foram registrados. RESULTADOS: No período do estudo, 31 pacientes foram incluídos no estudo, mas 9,7% (3 pacientes) não completaram o período mínimo de seguimento de 2 anos, sendo excluídos da análise, resultando em 28 pacientes ao final. O tempo médio de seguimento dos pacientes que completaram o estudo foi de 3 anos (± 9 meses). Dos 28 pacientes, 28,6% (8) eram do sexo masculino. A média de idade no ato cirúrgico foi de 10 anos e 7 meses ( ± 20 meses). As cirurgias duraram em média 247 ( ± 68) minutos de pele a pele. Foram retirados em média 1,7 corpos vertebrais. Os pacientes receberam em média 0,6 concentrados de hemácias durante o procedimento. O tempo de internação médio foi de 14 ( ± 27) dias. Os pacientes tinham em média cifose de 130º ( ± 36) no pré-operatório, que foi corrigida para 56º (± 29) em média no pós-operatório imediato e se manteve como 60º ( ± 30) após dois anos. Houve necessidade de reoperação em 67,8% (19) dos pacientes. Desses, 64,2% (18) pacientes necessitaram de reoperações para limpeza cirúrgica e desbridamento e 17,8% (5) dos pacientes necessitaram de retirada do material de síntese para controle da infecção. Houve perda de redução e pseudoartrose em 10,7% (3) dos pacientes. Houve melhora estatisticamente significante (p < 0,001) de 5 pontos em média na qualidade de vida utilizando-se o QG e 8 pontos utilizando-se o MNM, principalmente devido ao componente de saúde física das escalas. CONCLUSÃO: Apesar das altas taxas de reoperação, a cifosectomia demonstrou ser um método eficiente para melhora de qualidade de vida relacionada à saúde nesses pacientes / INTRODUCTION: Severe myelomeningocele-related kyphosis is a complex deformity that demands surgical treatment, with high complication rates. OBJECTIVES: The objective of this study is to evaluate the impact of the kyphectomy on the health-related quality of life of affected patients. METHODS: This is prospective study of a case series of patients operated by the authors at three institutions in São Paulo, Brazil, between 2012 and 2013. The surgical technique used was the one originally described by Dunn-McCarthy, in which posterior fixation is made using \"S-shaped\" rods, inserted through the foramens of S1, associated with pedicle screws in the thoracic spine. All patients were operated by the same team of five surgeons. Cobb angles before and after surgery, surgical time, hospital stay and transfused blood volume were registered. The patients\' caregivers answered both the generic (core) and the specific (neuromuscular module) PedsQL questionnaire before and 2 years after surgery. All adverse events were registered. RESULTS: In the study period, 31 patients were operated but 9,7% (3) were lost for follow up and therefore excluded from the analysis. They were followed-up for 3 years (± 9 months). The average age at surgery of the remaining 28 patients was 10 years and 7 months, and 28,6% (8) patients were males. The surgeries lasted on average 247 ( ± 68) minutes from skin to skin. The mean hospitalization time was 14 (± 27) days. On average, 1.7 vertebral bodies were removed per patient. The mean follow-up time of patients who completed the study was 3 years ( ±9 months). The patients had on average 130º (± 36) kyphosis in the preoperative period, that was corrected to 56º ( ± 29) in the immediate postoperative period and remained as 60º ( ± 30) after two years. Reoperation was needed in 67,8% (19 patients), 64,2% (18) of these for surgical cleaning and debridement. 17,8% (5) patients needed implant removal to control infection. There was loss of reduction and pseudoarthrosis in 10,7% (3) of the patients. There was a significant improvement (p < 0,001) of 5 points on average in the generic and 8 in the neuromuscular PedsQL questionnaires, mainly due to the physical health component of the scales. CONCLUSIONS: Kyphectomy improves health-related quality of life in these patients with myelomeningocele, despite the high reoperation rate

<p>Uvod: Sindrom lumbalne radikulopatije obuhvata disfunkciju nervnog korena lumbalne kičme, prouzrokovano kompresijom, nastalom usled hernijacije (protruzije, prolapsa) intervertebralnog diska ili zbog inflamatornih i degenerativnih promena (najče&scaron;će osteofita) u foraminalnom otvoru. Kvalitet života predstavlja savremeni koncept posmatranja ishoda oboljenja i uspe&scaron;nosti terapijske procedure kako u svim oblastima medicine, tako i u problematici lumbalne radikulopatije.<br />Cilj: Proceniti kvalitet života operativno i neoperativno lečenih pacijenata sa lumbalnom radikulopatijom na početku lečenja i 3 meseca, odnosno 6 meseci nakon sprovedene medicinske rehabilitacije.<br />Metode: Istraživanje predstavlja prospektivnu kliničku studiju kojom je analiziran kvalitet života bolesnika sa lumbalnom radikulopatijom. Obuhvaćen je randomiziran i stratifikovan uzorak pacijenata sa lumbalnom radikulopatijom diskalne geneze starosti 20 do 65 godina, oba pola (n=100), lečenih u Specijalnoj bolnici za progresivne mi&scaron;ićne i neuromi&scaron;ićne bolesti Novi Pazar. Jedna grupa ispitanika (n=50) lečena je isključivo neoperativnim metodama, dok je druga grupa bolesnika (n=50) lečena hirur&scaron;kim i neoperativnim metodama. Kod svih pacijenata sproveden je konzervativni tretman primenom fizikalnih procedura, kineziterapijskih procedura, ergonomske edukacije. Medikamentna terapija je kod svih bila identična. Za procenu stanja pacijenata, kvaliteta života i efekta rehabilitacionog tretmana kori&scaron;ćena su dva standardizovana upitnika: op&scaron;ti zdravstveni upitnik Medical Outcomes Study Short Form 36 (SF 36) i upitnik specifičan za oboljenje The Oswestry Disability Index (ODI).<br />Rezultati: Vrednosti SF-36 upitnika prikazanih sumarnim fizičkim (SFS) i mentalnim (SMS) skorom, i kod neoperativno lečenih ispitanika (FSFS=450,221 i p&lt;0,001; FSMS=106,543 i p&lt;0,001), ali i kod operativno lečenih (FSFS=490,721 i p&lt;0,001; FSMS=72,055 i p&lt;0,001) značajno su se menjale u toku ispitivanja. Vrednosti SFS kod neoperativno lečenih pacijenata (početak tretmana, 3 meseca, 6 meseci): 35,5 / 44,7 / 50,8; kod operativno lečenih: 28,8 / 42,8 / 49,2. Vrednosti SMS kod neoperativno lečenih pacijenata: 40,6 / 44,8 / 52,6; kod operativno lečenih: 37,8 / 45,2 / 52,5.<br />Najveće pobolj&scaron;anje SFS, kod obe grupe pacijenata, je registrovano u prva tri meseca od početka rehabilitacionog tretmana, dok je najveći napredak SMS registrovan u prva tri meseca od početka rehabilitacionog tretmana kod druge grupe pacijenata.<br />Vrednosti skora Osvestri indeksa nesposobnosti (ODI), i kod pacijenata prve grupe (F=432,810 i p&lt;0,001), ali i kod pacijenata druge grupe (F=1341,180 i p&lt;0,001) značajno su se menjale u toku ispitivanja. Vrednosti ODI kod neoperativno lečenih pacijenata su: 51,5% / 36% / 22,5%; a kod pacijenata druge grupe: 56,1% / 38,9% / 23,7%. Najveće pobolj&scaron;anje je registrovano u prva tri meseca od početka rehabilitacionog tretmana kod druge grupe pacijenata. Postoje statistički značajne korelacije glavnih sumarnih skorova i domena SF-36 (SFS i SMS) i ODI skorova.<br />Zaključak: Kvalitet života i funkcionalni status i neoperativno i operativno lečenih pacijenata je značajno bolji u komparaciji stanja, na 3 meseca i na 6 meseci u odnosu na početak rehabilitacije, kao i na 6 meseci u odnosu na stanje na 3 meseca.</p> / <p>Introduction: The syndrome of lumbar radiculopathy involves dysfunction of nerve roots of the lumbar spine, caused by compression, resulting due to herniation (protrusion, prolapse) intervertebral disc, or due to inflammatory and degenerative changes (usually osteophytes) in foraminal opening. Quality of life is the modern concept of observing the outcome of disease and therapeutic procedures in performance in all areas of medicine, as well as the problems of lumbar radiculopathy.<br />Aim: Assess the quality of life for surgically and conservatively treated patients with lumbar radiculopathy at initiation of treatment and 3 months, and 6 months after conducting medical rehabilitation.<br />Methods: The study is a prospective clinical study, which analyzed the quality of life of patients with lumbar radiculopathy. Also included is randomized and stratified sample of patients with lumbar radiculopathy of discal genesis aged 20 to 65 years, of both sexes (n=100) treated at the Special Hospital for progressive muscular and neuromuscular diseases Novi Pazar. One group of patients (n=50) were treated exclusively non-surgical methods, while the second group of patients (n=50) treated with surgical and non-surgical methods. In all patients was conducted by applying the conservative treatment of physical procedures, kinesitherapy procedures, ergonomic education. Medication treatment is at all were identical. To assess the condition of patients, quality of life and the effect of rehabilitation treatment used two standardized questionnaires: a general health questionnaire Medical Outcomes Study Short Form 36 (SF 36) and disease-specific questionnaire The Oswestry Disability Index (ODI).<br />Results: Values SF-36 questionnaire presented summary physical (SFS) and mental (SMS) scores, with non-surgical treated subjects (FSFS=450.221, p&lt;0.001; FSMS=106.543, p&lt;0.001), but also at surgical treated (FSFS=490.721, p&lt;0.001; FSMS=72.055, p&lt;0.001) were significantly changed during the study. Values at SFS non-surgical treated patients (beginning of treatment, 3 months, 6 months): 35.5 / 44.7 / 50.8; at surgical treated: 28.8 / 42.8 / 49.2. Values SMS with the non-surgical treated patients: 40.6 / 44.8 / 52.6; with surgical treated: 37.8 / 45.2 / 52.5. The biggest improvement of SFS, in both groups of patients were registered in the first three months of the start of the rehabilitation treatment, while the biggest progress SMS is registered in the first three months of the start of treatment in other patient groups. The Oswestry Disability Index (ODI) values score, in patients of the first group (F=432.810, p&lt;0.001), and in second group of patients (F=1341.180, p&lt;0.001) were significantly changed during the study. ODI values at non-surgical treated patients were: 51.5% / 36% / 22.5%; the second group of patients: 56.1% / 38.9% / 23.7%. The bigest improvement was registered in the first three months of the start of treatment in second group patients. There are statistically significant correlations main summary scores and SF-36 domains (SFS and SMS) and ODI scores.<br />Conclusion: The quality of life and functional status of both groups patients was significantly better in comparison to the situation, at 3 months and 6 months compared to the beginning of rehabilitation, as well as at 6 months compared to 3 months.</p>

This research investigates the synthesis and manufacture of shape-memory polymer (SMP) systems for use in biomedical and commodity applications. The research centers on improving the mechanical properties of thermoset acrylate copolymers with memory properties at reasonable cost through various design and manufacturing techniques: high-strain polymer synthesis and radiation crosslinking. The research assesses combinations of linear monomers and a low density of crosslinker to characterize new functional materials and optimize emerging mechanical properties such as the glass transition temperature (Tg) and rubbery modulus (ER). Exploring materials with large recoverable strains, a model copolymer of photo-polymerized methyl acrylate (MA), isobornyl acrylate and crosslinker bisphenol A ethoxylate dimethacrylate was shown to strain above 800%, twice the previously published value for SMPs, and recover fully. In the quest to maximize fully recoverable strains, a new hybrid molecule nicknamed Xini, which serves as both an initiator and a crosslinker, was also theorized, synthesized, polymerized into SMP networks and characterized. In the past, thermoset SMPs were made into complex shapes using expensive top-down techniques. A block of polymer was made and custom machining was required to craft complex parts. This prohibited devices in cost-competitive commodity application spaces. This research has proposed and validated a new method for accurately tuning the thermomechanical properties of network acrylates with shape-memory properties: Mnemosynation, eponymously named for the Greek goddess of memory. This novel manufacturing process imparts long term 'memory' on an otherwise amorphous thermoplastic material utilizing radiation-induced covalent crosslinking, and can be likened to Vulcanization, which imparts strength on natural rubber utilizing sulfur crosslinks. Adjustment of ER in the range from below 1 MPa to above 13 MPa has been demonstrated. ER was tailored by varying both radiation dose between 5 and 300 kGy and crosslinker concentration between 1.00 and 25.0 wt%. Tg manipulation was demonstrated between 23 ˚C and 70 ˚C. Mnemosynation combines advances in radiation grafting and acrylic SMP synthesis to enable both traditional plastics processing (blow molding, injection molding, etc.) and control of thermoset shape-memory properties. Combining advances in both high strain polymer synthesis and radiation crosslinking, a new paradigm in SMP composites manufacture-namely, that materials can be designed to enhance strain capacity at moderate stress, rather than maximum strength-was established. Various fibers with very different mechanical properties were impregnated with SMPs and thermo-mechanically assessed to develop an understanding of the technical parameters necessary to craft self-adjusting, multi-actuated, SMP-fiber composite orthopedic casts. This exploration syncs with the overarching aim of the research, which is to understand the fundamental scientific drivers necessary to enable new devices mass-manufactured from acrylate copolymers and optimize their emerging mechanical properties.

Introduction & Objectifs : Pour assurer l’analgésie postopératoire, l’anesthésiste dispose, en plus des différentes classes de médicaments administrés par voie orale ou intraveineuse, de diverses techniques pour bloquer l’influx nerveux douloureux en administrant les anesthésiques locaux (AL) de manière centrale ou périphérique. La ropivacaïne (ROP), un AL à longue durée d’action, est un médicament de première intention partout dans le monde, en raison de sa grande efficacité et de son faible risque de toxicité. Contrairement à certains pays, la ROP n'est toujours pas indiquée au Canada pour la rachianesthésie (bloc central) en raison d'un manque de données probantes. Jusqu'à présent, les efforts de recherche ont essentiellement porté sur la sécurité ainsi que sur la durée d’action du médicament lorsqu’administré par voie spinale. De plus, les doses optimales de ROP pour l’anesthésie régionale périphérique ne sont pas encore précisément connues. La posologie devrait être adaptée au site d’administration ainsi qu’à l’intensité et la durée du stimulus produit par la chirurgie. Ultimement, cela permettrait aux cliniciens d’identifier le régime optimal en fonction des facteurs démographiques qui pourraient affecter la pharmacocinétique (PK) et la pharmacodynamie (PD) de l’AL (objectif global de ces travaux). Validation de la Méthode Analytique Manuscrit 1 : Une méthode analytique spécifique et sensible permettant de déterminer les concentrations plasmatiques de ROP a d’abord été optimisée et validée. Validation du Biomarqueur Manuscrit 2 : Nous avons ensuite mis au point et évalué la fiabilité d’une méthode quantitative basée sur la mesure du seuil de perception sensorielle (CPT) chez le volontaire sain. Ce test nécessite l’application d’un courant électrique transcutané qui augmente graduellement et qui, selon la fréquence choisie, est capable de stimuler spécifiquement les fibres nerveuses impliquées dans le cheminement de l’influx nerveux douloureux. Les résultats obtenus chez les volontaires sains indiquent que la mesure CPT est fiable, reproductible et permet de suivre l’évolution temporelle du bloc sensitif. Études cliniques Manuscrit 3 : Nous avons ensuite caractérisé, pendant plus de 72 h, l’absorption systémique de la ROP lorsqu’administrée pour un bloc du nerf fémoral chez 19 patients subissant une chirurgie du genou. Le modèle PK populationnel utilisé pour analyser nos résultats comporte une absorption biphasique durant laquelle une fraction de la dose administrée pénètre rapidement (temps d’absorption moyen : 27 min, IC % 19 – 38 min) dans le flux sanguin systémique pendant que l’autre partie, en provenance du site de dépôt, est redistribuée beaucoup plus lentement (demi-vie (T1/2) : 2.6 h, IC % 1.6 – 4.3 h) vers la circulation systémique. Une relation statistiquement significative entre l’âge de nos patients et la redistribution de l’AL suggère que la perméabilité tissulaire est augmentée avec l’âge. Manuscrit 4 : Une analyse PK-PD du comportement sensitif du bloc fémoral (CPT) a été effectuée. Le modèle développé a estimé à 20.2 ± 10.1 mg la quantité de ROP nécessaire au site d’action pour produire 90 % de l’effet maximal (AE90). À 2 X la AE90, le modèle prédit un début d’action de 23.4 ± 12.5 min et une durée de 22.9 ± 5.3 h. Il s’agit de la première étude ayant caractérisé le comportement sensitif d’un bloc nerveux périphérique. Manuscrit 5 : La troisième et dernière étude clinique a été conduite chez les patients qui devaient subir une chirurgie du genou sous rachianesthésie. Tout comme pour le bloc du nerf fémoral, le modèle PK le plus approprié pour nos données suggère que l’absorption systémique de la ROP à partir du liquide céphalo-rachidien est biphasique; c.à.d. une phase initiale (T1/2 : 49 min, IC %: 24 – 77 min) suivie (délai: 18 ± 2 min) d'une phase légèrement plus lente (T1/2 : 66 min, IC %: 36 – 97 min). L’effet maximal a été observé beaucoup plus rapidement, soit aux environs de 12.6 ± 4.9 min, avant de revenir aux valeurs de base 210 ± 55 min suivant l’administration de l’agent. Ces données ont permis d’estimer une AE50 de 7.3 ± 2.3 mg pour l'administration spinale. Conclusion : En somme, ces modèles peuvent être utilisés pour prédire l’évolution temporelle du bloc sensitif de l’anesthésie rachidienne et périphérique (fémorale), et par conséquent, optimiser l’utilisation clinique de la ROP en fonction des besoins des cliniciens, notamment en ce qui a trait à l’âge du patient. / Background & Objectives: To provide postoperative analgesia, the anesthesiologist has at his disposal a panel of different medications and also regional techniques of neural blockade. Loco-regional analgesia (central or peripheral) blocks conduction of painful influx to the central nervous system by the use of local anesthetics (LA). Among these drugs, ropivacaine (ROP), has an enormous potential given is long-acting efficacy and low incidence of toxicity. Currently, ROP is not licensed for use in spinal anesthesia (central block) in all countries due to a lack of data from controlled clinical trials. So far, research efforts on this topic have mainly focused on safety and dose-finding issues. In addition, the most appropriate dose for a peripheral nerve block has never been estimated empirically. Dosing recommendation for LAs should be site-specific and adapted to the intensity of the stimuli produced by a surgery and to the duration of analgesia required. Ultimately, these should guide clinicians in identifying the most appropriate block for the individual patients by taking into account demographic factors that may affect the pharmacokinetics (PK) and pharmacodynamics (PD) of LA overall objective of the current research) Analytical Method Validation Manuscript 1: First, a specific and sensitive assay has been developed and validated for the determination of ROP in human plasma. Biomarker Validation Manuscript 2: Second, the reliability of a neurostimulator measuring current perception threshold (CPT) was assessed in healthy volunteers. The device uses a constant transcutaneous electrical sine wave stimulus at different frequencies specific to pain-conducting fibers. Our results suggest that CPT are reliable and can be applied to characterize, in a quantitative manner, the sensory onset of a peripheral nerve block in a clinical setting. Clinical Studies Manuscript 3: The systemic absorption of ROP after a femoral nerve block in orthopedic patients was then characterized using extended rich PK-sampling, i.e. up to 4 days post-dosing. Our model used for data analysis confirms that, in a similar manner to neuraxial sites of LAs injection, the systemic absorption of ROP from the femoral space is biphasic, i.e. a rapid initial phase (mean absorption time of 25 min, % CI: 19 – 38 min) followed by a much slower phase (half-life (T1/2) of 3.9 h, % CI: 2.9 – 6.0 h). A significant age-related increase in the permeability of the LA was also observed in our elderly patients (n = 19, age = 62.6 ± 7.1 yr). Manuscript 4: A population PK-PD analysis of the sensory anesthesia (CPT) of ROP using our PK model was also performed. The effect-site amount producing 90% of the maximum possible effect (AE90) was estimated as 20.2 ± 10.1 mg. At 2 x AE90, the sigmoid Emax model predicted an onset time of 23.4 ± 12.5 min and a duration of 22.9 ± 5.3 h. To the best of our knowledge, this is the first PK-PD model developed for a peripheral nerve block. Manuscript 5: In the third and last study, a similar approach was used to characterise the PK-PD relationship of intrathecally administered ROP in patients undergoing minor lower limb surgery. The biphasic release of the agent from the intrathecal space was modeled using a rapid initial absorption phase (T1/2 of 49 min, % CI: 24 – 77 min) followed (lag-time of ~ 18 ± 2 min) by a slightly slower input rate (T1/2 of 66 min, % CI: 36 – 97 min). ROP maximal response was observed within 12.6 ± 4.9 min of dosing, with a subsequent return to baseline 210 ± 55 min after the administration of the LA. The effect-site amount producing 50 % of the Emax (AE50) was estimated at 7.3 ± 2.3 mg. Conclusion: Altogether, the proposed models can be used to predict the time-course of sensory blockade after a femoral nerve block and spinal anesthesia using ROP and to optimize dosing regimen according to clinical needs with regard to important cofactors such as age.

Les transfusions sanguines sont fréquemment employées pour corriger l’anémie secondaire à une arthroplastie de la hanche ou du genou. Il n’y a cependant pas consensus sur les indications de transfuser. La tendance actuelle est d’utiliser une stratégie transfusionnelle restrictive (soit un seuil de 75-80 g/L d’hémoglobine) mais les conséquences d’une telle pratique sur la récupération fonctionnelle et la qualité de vie des patients sont mal connues. Dans un premier temps, nous avons caractérisé la pratique transfusionnelle au Centre hospitalier de l’Université de Montréal (CHUM). Notre hypothèse était que, devant l’imprécision des recommandations, la pratique transfusionnelle serait variable. Une étude rétrospective de 701 dossiers de patients ayant subi une arthroplastie de la hanche ou du genou a été réalisée. Nous avons observé que les transfusions étaient utilisées de la même façon dans les trois hôpitaux et que les médecins basaient leur décision de transfuser principalement sur un seul chiffre, la concentration d’hémoglobine, adoptant une stratégie restrictive. Soixante-six pourcent des patients avaient une concentration d’hémoglobine inférieure à 100 g/L au départ de l’hôpital. Dans un deuxième temps, nous avons évalué l’impact de cette anémie postopératoire sur la récupération fonctionnelle et la qualité de vie des patients. Notre hypothèse était qu’il existe une concentration d’hémoglobine en dessous de laquelle celles-ci sont atteintes. Une étude de cohorte prospective et observationnelle a été menée chez 305 patients regroupés selon leur concentration d’hémoglobine postopératoire. Les groupes d’hémoglobine (≤ 80, 81-90, 91-100 et > 100 g/L) étaient similaires dans l’évolution de la distance de marche en six minutes, de l’évaluation de l’effort fourni, de la force de préhension et des scores de qualité de vie. L’anémie modérée n’est donc pas associée à une atteinte de la récupération fonctionnelle et de la qualité de vie à court terme. D’autres études devront déterminer les conséquences à long terme d’une stratégie transfusionnelle restrictive sur ces patients. / Red blood cell transfusions are frequently used to treat anemia after total hip or knee arthroplasties. The indications for transfusions remain unclear despite published guidelines. Clinicians have adopted a restrictive transfusion threshold (75-80 g/L) but the consequences of such a strategy on functional outcome and quality of life are not known. First, we characterized the transfusion practice inside the Centre hospitalier de l’Université de Montréal (CHUM). Our hypothesis was that transfusion practice varies inside the CHUM due to uncertainty. A retrospective study of 701 charts of patients operated for a hip or knee arthroplasty was conducted. We observed that there was no difference among hospitals regarding the way transfusions are used and that physicians mainly based their decision to transfuse on a single variable, the hemoglobin concentration, adopting a restrictive transfusion strategy. Sixty-six percent of patients had a hemoglobin concentration under 100 g/L after surgery. Second, we evaluated the impact of this postoperative anemia on functional outcome and quality of life. We hypothesized that a threshold hemoglobin concentration exists below which these become impaired. A prospective, observational cohort study was conducted in 305 patients categorized in groups according to their postoperative hemoglobin concentration. Hemoglobin groups (≤ 80, 81-90, 91-100 and > 100 g/L) were similar in the evolution of the distance walked in six minutes, perception of effort, maximal dominant hand strength and quality of life scores. Thus, moderate anemia is not associated with an impaired functional recovery or quality of life early after hip and knee arthroplasties. Further studies will be required to determine the long-term consequences of a restrictive transfusion strategy in these patients.

CAPES; CNPq / O emprego da Manufatura Aditiva (AM) vem aperfeiçoando a confecção de produtos assistivos customizados, mas para a sua utilização se faz necessário gerar o modelo geométrico digital. Uma das alternativas para obtê-lo é com o uso de escâneres 3D. Após a digitalização, dificilmente o resultado alcançado, geralmente uma malha digital da superfície 3D do modelo físico, pode ser utilizado diretamente na AM. Para tanto, é exigido alguns tratamentos desta tmalha em programas CAD (Computer-Aided Design) 3D. Algumas dessas ferramentas, tanto os escâneres 3D quanto os programas CAD 3D, são viáveis, mas de alto custo. Além disso, a etapa de tratamento da malha não é abordada nos estudos encontrados, prejudicando a disseminação dessas tecnologias. Desta forma, o presente trabalho propõe um método de baixo custo para o desenvolvimento de órtese de membro superior visando a fabricação por AM, tendo como foco principal a abordagem das etapas de tratamento da malha e modelagem da órtese. Como objeto de estudo foram utilizados 12 moldes em gesso de punho, mão e dedos confeccionados por um terapeuta ocupacional. A digitalização dos moldes em gesso ocorreu com o emprego de dois sistemas de baixo custo, o sensor do Kinect 360 e o programa Remake, e um de alto custo para servir como referência, o escâner REVscan. Para as etapas de tratamento da malha e modelagem da órtese foram utilizados dois programas CAD 3D gratuitos: Blender e Meshmixer. Os digitalizadores de baixo custo geraram malhas que foram validadas ao compará-las as geradas pelo REVscan. Diferentemente do Remake, o Kinect gerou malhas sem defeitos e em menor tempo, porém, apresentou os maiores desvios dimensionais e os maiores tamanhos de arquivo. Os defeitos apresentados nas malhas geradas pelo Remake foram do tipo lacunas e foram corrigidos com êxito pelos programas CAD 3D. Na etapa de tratamento da malha foi constatada a relevância da etapa de suavização das bordas no resultado final da órtese. Os resultados ressaltaram a importância da etapa de tratamento e correção das malhas para o desenvolvimento de produtos assistivos visando a fabricação por AM. De forma geral, foi possível desenvolver órteses personalizadas utilizando as ferramentas de baixo custo. Os procedimentos descritos neste estudo podem auxiliar no desenvolvimento de produtos assistivos e propiciar a disseminação desse conhecimento nas empresas e instituições dispensadoras de órteses. / The use of the Additive Manufacturing (AM) has improved the production of customized assistive products, but its use needs to generate the digital geometric model first. One of the alternatives to get it is with the use of 3D scanners. After the scanning, hardly the result achieved, usually a digital STL (stereolithography format) mesh of the 3D surface of the physical model, can be used directly in AM. Therefore, it is required some mesh treatments in 3D CAD (Computer-Aided Design) programs. Some of these tools, both 3D scanners and 3D CAD programs, are feasible but high cost. In addition, the mesh treatment step is not addressed in the studies found, hampering the spread of these technologies. In this way, the present work proposes a low cost method for the development of upper limb orthosis aimed at manufacturing by AM, focusing mainly on the steps of mesh treatment and orthosis modeling. As object of study were used 12 gypsum molds of wrist, hand and fingers made by an occupational therapist. The 3D digitizing of plaster casts occurred using two low-cost systems, the Kinect 360 sensor and the Remake program, and a high-cost scanner to serve as a reference, the REVscan. For the steps of mesh treatment and orthoses modeling, two free 3D CAD programs were used: Blender and Meshmixer. The lowcost scanners generated meshes that were validated by comparing them to those generated by REVscan. Unlike Remake, Kinect generated non-defective meshes and in less time, however, presented the largest dimensional deviations and the largest file sizes. The defects presented in the meshes generated by Remake were of the gaps type and were corrected successfully by 3D CAD programs. In the mesh treatment step, it was verified the relevance of the procedure of smoothing the edges in the final orthosis result. The results highlighted the importance of the meshes treating step for the development of assistive products aiming the manufacture by AM. In general, it was possible to develop customized orthoses using low-cost tools. The procedures described in this study can assist in the development of assistive products and facilitate the dissemination of this knowledge in companies and institutions that provide orthosis.

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