A utilização de implantes cirúrgicos para artroplastia de quadril com prótese de recapeamento da cabeça femoral como substituto ósseo é um procedimento que tem sido realizado em 35% dos casos de Osteoartrose nos EUA. Entretanto, o atrito da broca e o aumento da temperatura durante a usinagem da cabeça femoral são responsáveis pelo possível aquecimento do tecido ósseo, podendo provocar a necrose óssea térmica. Neste sentido, o desenvolvimento de novos ferramentais e metodologias para minimizar os danos térmicos do atrito torna-se importante. Diante disso, o presente estudo teve como objetivo verificar se há a ocorrência de necrose óssea em um procedimento de furação óssea utilizando o dispositivo EQUITRON; Mod.ES 2200, desenvolvido no LTC-EESC-USP. Para tal, utilizamos 4 amostras de costela bovina removidas após a morte do animal, que foram furadas com broca de aço inoxidável (HSS-SKF), de 8 milímetros, sem irrigação externa. As amostras foram furadas com rotações de 100, 1000, 1200 e 2500 RPM, aferidas por tacômetro foto/contato digital da marca MINIPA, MDT-2238, e com avanço controlado de 80 mm/min (dispositivo da marca-EQUITRON; MOD.ES 2200; RPM 2800; Potência 0,30; Torque 1,6 Nm). Foram mensuradas as temperaturas iniciais da broca e da amostra e a final da amostra com termômetro digital, marca-MEDISANA®. Após a furação foram confeccionadas lâminas histológicas (HE) do tecido ósseo, preparadas de acordo com a metodologia apropriada, para posterior qualificação e quantificação da ocorrência de necrose óssea térmica através de imagens captadas por microscopia óptica (Olympus BX 41TF - Made Japan) utilizando-se o programa Motic Images Plus 2.0 para a captura das imagens. Os valores de temperaturas aferidos na amostra após a furação apresentaram relação positiva com a RPM utilizada, isto é, quanto maior a rotação, maior foi a temperatura observada. Apenas a amostra furada a 2500 RPM ultrapassou a temperatura de referencia para a gênese da osteonecrose térmica, que é de 47ºC. As análises histológicas apresentaram uma baixa predominância de células picnóticas e lacunas, sugerindo menor dano tecidual. Os resultados obtidos no presente estudo sugerem que o dispositivo (furadeira) desenvolvido no LTC-EESC-USP para a realização das furações nas amostras ósseas em testes de bancada foi eficiente em minimizar a ocorrência de necrose óssea térmica, até mesmo em condições de temperatura acima do limite fisiológico aceitável. / The utilization of surgical implants for hip arthroplasty with a resurfacing prosthesis of the femoral head as a bone substitute have been conducted in 35% of osteoarthrosis cases in the USA. However, the friction of the drill and the increase in the temperature during the machining of the femoral head can possibly heat the bony tissue and provoke a thermal bone necrosis. The development of new tools and methodologies for minimizing the thermal damage of the friction has become fundamental. The present study analyzes the occurrence of bone necrosis in a procedure of bone drilling that uses an EQUITRON device, Mod. ES 2200, developed at the LTC-EESC-USP. Four samples of bovine ribs removed after the death of the animal were used for the tests. They were drilled by an 8mm stainless-steel drill (HSS-SKF) with no external irrigation, at 100, 1000, 1200 and 2500 RPM calibrated by a MINIPA, MDT-2238 digital photo/contact tachometer and whose 80mm/min. advance (EQUITORN device; MOD.ES 2200; RPM 2800; 0.30 Potency and 1,6Nm torque) was controlled. The initial temperatures of the drill and the sample and the final temperature of the sample were measured by a MEDISANA digital thermometer. After drilling, histological blades (HE) were produced from the bony tissue and prepared according to the adequate methodology for further qualification and quantification of the occurrence of thermal bone necrosis through images captured by optical microscopy (Olympus BX 41TF - made in Japan) and Motic Images Plus 2.0 program. The values of the temperatures measured in the sample after drilling showed a positive relation with the RPM utilized, i.e., the faster the rotation, the higher the temperature. Only the sample drilled at 2500RPM exceeded the reference temperature (47ºC) for the genesis of the thermal osteonecrosis. The histological analyses revealed a low predominance of picnotic cells and gaps, which suggest minor tissue damage. The results show the device (drilling machine) developed at the LTC-EESC-USP for the drilling in the bone samples in workbench tests is efficient to minimize the occurrence of thermal bone necrosis, even at temperatures above the physiological acceptable limit.

Orientador: João Batista de Miranda / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T22:32:06Z (GMT). No. of bitstreams: 1 Yamada_NeideSumie_M.pdf: 1286859 bytes, checksum: 13049b157f58cc99cc1277c8a5174f29 (MD5) Previous issue date: 2012 / Resumo: Introdução: As infecções são uma das complicações mais temidas nas artroplastias de quadril e joelho. A falta de um registro nacional de artroplastias e a escassez de publicações nacionais sobre o tema leva ao desconhecimento sobre os fatores de risco desta complicação na população brasileira. Objetivo: O objetivo deste trabalho é identificar a incidência e os fatores de risco para infecções relacionadas com as artroplastias de quadril (PTQ) e joelho (PTJ) em pacientes do hospital das clínicas da Unicamp. Métodos: Foi realizado um estudo tipo caso-controle, retrospectivo, das PTQs e PTJs feitas no período de 2005 a 2009, onde foi revisado os prontuários e coletados estes dados: idade, sexo, peso, altura,tipo de cirurgia, tempo de duração da cirurgia, número de doses de antibioticoterapia profilática, tempo de internação pré e pós-operatório, tempo de sondagem vesical de demora, presença de comorbidades como hipertensão e diabetes, história de etilismo e tabagismo, infecções recentes e tardias. Resultados: Foram incluídas neste estudo 173 artroplastias, sendo 109 (63%) de quadril e 64 (37%) de joelho. A incidência de infecções nas PTQs foi de 6,4% e nas PTJs foi de 20,3%. Dentre os fatores de risco para infecção, os que tiveram correlação positiva foram o maior tempo de internação pós-operatório e o maior tempo total de internação. Conclusão: A incidência de infecções em prótese total de joelho e quadril foi considerada alta, acima da estabelecida na literatura. Os únicos fatores de risco que apresentaram correlação foram o tempo de internação pós- operatória e o tempo total de internação / Abstract: Introduction: Infections are one of the most challenging drawbacks in hip and knee Arthroplasty surgery. The lack of a national databank and the shortage of national paper about this issue, cause risk factors unknown among Brazilian people. Objective: To identitify incidence and risk factors ofinfection related to hip and knee Arthroplasty surgery, in a Brazilian teaching hospital. Method: A retrospective case-control study was performed between 2005 and 2009, to evaluate medical records of patients submitted to hip or knee Arthroplasty. Data collected was the following: age, gender, weight, heitght, kind of surgery, surgery duration, antibiotic drug doses number, hospitalization length, urinary catheter length, medical conditions (such diabetes, high bloodo pressure, smoking, drinking), acute and chronic infections. Results: It was included 173 patients, of which 109 (63%) were total hip arthroplasties and 64 (37%) were total knee arthroplasties. Hip arthrplasty infection rate was 6,4%, and Knee Arthroplasty infection rate was 20,3%. Among infection risk factors, total length of hospital stay and length of post-surgical hospital stay were the that presented significant correlation. Conclusion: Infection rates after hip and knee arthroplasties were considered high. The only risk factors that presented a significant correlation were total hospital stay length and post-surgical hospital stay length / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências da Cirurgia

Aim: To study patient-related functional outcome measures, implant survival and radiographic loosening after total wrist arthroplasty (TWA) using four different implants. To evaluate a new TWA design biomechanically and clinically. Methods: The studies included two cohort studies with prospectively collected data (n=206 and n=219), an anatomic and kinematic analysis in a cadaveric model and a pilot study (n=20). Results: The Maestro TWA had a significantly greater improvement of radial/ulnar deviation than the Biax and Remotion TWAs. Summarized patientrelated functional outcome was significantly better for the Maestro than for the Remotion TWA. Cumulative implant survival after 8 years was 94% for Remotion, and 95% for Maestro implants. Radiographic loosening five years postoperatively was present in 26% of the Biax wrists, 18% of those with Remotion, and 2% of those with Maestro. Following TWA with the new implant design in a cadaveric model, there were no statistically significant changes compared to a native wrist regarding flexion, extension, radial deviation, the extension/radial deviation component of the dart-thrower’s motion, or the circumduction range of motion. Clinically, there was significant improvement of COPM, PRWE and VAS pain scores. Wrist extension and ulnar deviation improved, while grip strength remained largely unchanged. Conclusions: TWA is a surgical procedure which may offer a high level of patient satisfaction. Implant design may affect patient-related functional outcome after TWA. Implant survival as well as the frequency of radiographic loosening differed considerably between the four types of implants and might be a result of different implant design. Kinematic analysis of the new TWA design suggests that a stable and functional wrist is achievable with this design. Surgical placement of the new total wrist implant was reproducible and the implant yielded good patient-related outcome measures in the short term. Since TWA is an evolving procedure, further studies are warranted in order to refine indications and the place for TWA in modern hand surgery.

Abstract High tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) are performed for the treatment of isolated medial osteoarthritis (OA) of the knee. In the treatment of knee OA, the incidence of osteotomies has decreased with the popularisation of knee arthroplasties, but it is still indicated in young and active patients. Results of HTO tend to deteriorate over the time and patients may need to undergo subsequent total knee arthroplasty (TKA). TKA after HTO is a demanding procedure, and the influence of previous osteotomy on the results of TKA is not defined. Results of UKAs are controversial. Single centre studies have shown good results, but arthroplasty registers report consistently inferior survivorships compared with TKAs. However, comparison of register survivals may be inadequate because differences in the demographics of the patients have not been taken into account. The aims of the current nationwide register-based study were to assess incidence of osteotomies and survivorship of HTO in the treatment of knee OA, and to compare survivorship of TKAs performed after HTO with primary TKAs between 1987 and 2008 in Finland. In addition, this study reports survivorship of UKAs over a 25 year period and compare it with the survival of cemented TKAs. Based on this study, the overall incidence of osteotomies has decreased, especially in females, in the treatment of knee OA during the last two decades. In the patients less than 50 years of age, the incidence of osteotomies has been stable or slightly increased. Register-based survivorship of HTO was inferior compared with smaller cohort studies and females and patients aged >50 years had the poorest results. The survivorship of TKA after osteotomy was slightly inferior compared with primary operations in general, but any clinical significance was minor. In this study UKA had inferior survivorship compared with TKA, even after adjusting for the age and gender of the patients. The reported survivorship of UKA was similar to those from available unadjusted arthroplasty register data. Surgeons should be made aware of this, but the reasons for incoherence with single-centre studies are not yet established and need further study. / Tiivistelmä Sääriluun katkaisu- ja kääntöleikkauksia (osteotomia) ja osatekonivelleikkauksia tehdään polven sisäsyrjän nivelrikon hoitamiseksi. Tekonivelleikkausten yleistyttyä osteotomioiden määrä on vähentynyt polven nivelrikon hoidossa, mutta niitä tehdään edelleen nuorille ja aktiivisille potilaille. Osteotomian jälkeen polveen voidaan joutua asentamaan kokotekonivel. Tämä leikkaus on vaativa, ja edeltävällä osteotomialla voi olla vaikutusta kokotekonivelleikkauksen tuloksiin. Polven sisäsyrjän nivelrikkoa voidaan hoitaa osteotomian ja kokotekonivelleikkauksen lisäksi osatekonivelellä. Polven sisäsyrjän osatekonivelleikkauksen tulokset ovat kuitenkin ristiriitaisia. Yksittäisissä tutkimuksissa on raportoitu hyvistä tuloksista, mutta tekonivelrekisterien raporteissa osatekonivelleikkauksen uusintaleikkausriski on kokotekonivelleikkausta selvästi suurempi. Tämän rekisteritutkimuksen tarkoituksena oli selvittää polven nivelrikon vuoksi tehtyjen osteotomialeikkausten määrän kehitystä ja polven nivelrikon vuoksi tehtyjen säären osteotomialeikkausten tuloksia Suomessa vuosina 1987–2008. Lisäksi tutkimuksessa selvitettiin samalla ajanjaksolla osteotomian jälkeisten kokotekonivelleikkausten uusintaleikkausriskiä verrattuna primaareihin tekonivelleikkauksiin ja polven osatekonivelleikkausten uusintaleikkausriskiä verrattuna polven kokotekonivelleikkauksiin. Tutkimuksessa todettiin seuraavaa: polven nivelrikon vuoksi tehtyjen osteotomialeikkausten määrä on kahden viimeksi kuluneen vuosikymmenen aikana vähentynyt, etenkin naispotilailla. Osteotomialeikkausten määrä on kuitenkin pysynyt samana tai hiukan noussut alle 50-vuotiailla. Tässä rekisteritutkimuksessa säären osteotomian jälkeisen tekonivelleikkauksen uusintaleikkausriski oli suurempi kuin pienemmissä tutkimussarjoissa keskimäärin. Lisäksi tutkimuksessa todettiin, että säären osteotomian jälkeisten kokotekonivelleikkausten uusintaleikkausriski on suurempi kuin primäärien kokotekonivelleikkausten, mutta eron kliininen merkitys on vähäinen. Osatekonivelten osalta todettiin, että iän ja sukupuolen mukaan vakioitujen osatekonivelleikkausten uusintaleikkausriski on suurempi kuin kokotekonivelleikkausten. Tulosten ero yksittäisten tutkimusten ja rekisterien välillä on kuitenkin suuri, mikä vaatii lisätutkimuksia.

Wear particle-induced inflammation leading to periprosthetic osteolysis remains a major cause of hip implant failure. As polyethylene particles from conventional metal-on-polyethylene implants have been associated with these failures, an interest in lower wear metal-on-metal (MM) bearings has emerged. However, the biological effects of nanometer-size chromium oxide particles, predominant type of wear particles produced by MM implants, remain mostly unknown. Therefore, this study aimed to determine the cytotoxicity of nanometer-size Cr2O3 particles on macrophages in vitro, by analyzing their effects on cell mortality and cytokine release and comparing them with those of similarly-sized alumina (Al2O3) particles (known to be relatively bioinert). Results showed that at high concentrations, nanometer-size Cr2O3 particles can be cytotoxic to macrophages, inducing significant decreases in total cell numbers and increases in necrosis. Results also showed that, at high concentrations, the cytotoxicity of Cr2O3 particles was overall higher than that of Al2O3 particles, even though Cr2O3 and Al2O3 are both stable forms of ceramic materials. However, it appeared to be lower than that of previously reported conventional polyethylene and CoCrMo particles. Therefore, chromium oxide particles may not be the main culprit in initiating the inflammatory reaction in MM periprosthetic tissues.

Introdução: As alterações anatômicas do fêmur proximal ou do acetábulo, como as decorrentes das sequelas da epifisiólise do fêmur proximal, da displasia do quadril da doença de Legg-Perthes-Calvé, podem levar ao desenvolvimento da artrose do quadril. No entanto, em torno de 80% dos indivíduos que desenvolvem essa doença têm uma anatomia óssea considerada normal. Ainda assim, surgiu a hipótese que alterações sutis do fêmur proximal ou do acetábulo, denominadas, respectivamente, cam e pincer, poderiam gerar um contato anormal entre essas estruturas ósseas, desencadear lesão condral e, como consequência, a artrose do quadril. Esse mecanismo foi denominado impacto fêmoro-acetabular. No entanto, a comprovação da relação entre o impacto e a artrose do quadril depende da uniformização dos critérios diagnósticos do cam e do pincer, ainda escassa e variável na literatura. Dessa forma, será possível a definição da prevalência e história natura do impacto fêmoro-acetabular e da sua relação com a artrose do quadril. Objetivo: Avaliar a prevalência do impacto fêmoro-acetabular tipo cam e tipo pincer em uma amostra de indivíduos assintomáticos. Pacientes e Métodos: Foram estudados 106 indivíduos assintomáticos (65 homens e 41 mulheres), com idade entre 20 e 40 anos. A condição determinante para a inclusão no estudo foi à ausência de história de dor no quadril ao longo da vida. Foram obtidas radiografias em ântero-posterior e Dünn 45°. A presença de cam foi determinada por um ângulo alfa, arbitrado, de 55° e a presença de pincer, quando observado o sinal da parede posterior e/ou o sinal de crossover. Resultados: Foi observada prevalência de cam de 29%; o sinal do crossover e da parede posterior ocorreram, respectivamente, em 20% e 29% dos indivíduos estudados. Pelo menos uma das imagens de impacto fêmoro-acetabular estava presente em 65% dos indivíduos da amostra. Conclusão: A prevalência encontrada das imagens de impacto fêmoro-acetabular (65%) está acima daquelas relatadas na literatura. É necessária a ampliação do estudo para confirmar os resultados encontrados e a realização de estudos prospectivos bem controlados para avaliar o papel do cam e do pincer no desenvolvimento da artrose do quadril. / Background: Anatomical abnormalities of the proximal femur or the acetabulum, such as those resulting from the consequences of slipped epiphyses of the proximal femur, the hip dysplasia of Legg-Calve-Perthes disease, could lead to the development of hip osteoarthrosis. Nevertheless, around 80% of individuals who develop this condition have a bone anatomy considered normal. Still, the hypothesis arose that subtle alterations of the proximal femur or the acetabulum, called, respectively, cam and pincer, could generate an abnormal contact between these bony structures, triggering chondral lesion and as a consequence, arthritis of the hip. This mechanism has been named femoroacetabular impingement. Nevertheless, evidence of the relationship between the impact and osteoarthritis of the hip depends on the standardization of diagnostic criteria of cam and pincer, still scarce and variable in the literature. Thus it will be possible to define the prevalence and natural history of femoroacetabular impingement and its relationship with hip osteoarthrosis. Aim: To determine the prevalence of cam-type and pincer-type femoroacetabular impingements in asymptomatic subjects. Patients and Methods: Were studied 106 asymptomatic subjects (65 males and 41 females) aged between 20 and 40 years. The determining condition for inclusion in the study was the absence of history of hip pain throughout life. Radiographs were obtained in anteroposterior pelvic view and Dunn 45° view. The presence of cam was determined by an angle alpha, arbitrated, 55 ° and the presence of pincer when the observed the posterior wall and / or crossover signs. Results: A prevalence of 29% of cam, and 20% and 29% of crossover sign and posterior wall sign respectively was found. At least, one of those radiographic signs of femoroacetabular impingement was found in 65% (68) of the cases. Conclusion: In conclusion, the prevalence of images of femoroacetabular impingement (65%) is above those reported in the literature. Increase of the study is necessary to verify the results found, and the performance of well-controlled prospective studies to evaluate the role of the cam and pincer in the development of osteoarthritis of the hip.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22831号 / 医博第4670号 / 新制||医||1047(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 安達 泰治, 教授 別所 和久, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Surgical interventions on the hip joint have greatly increased over the past decade, with the cumulative cost total hip arthroplasties (THA) alone exceeding $400B/year by 2020. Although positive patient-reported outcomes and satisfaction after THA and hip preservation for cam femoroacetabular impingement (FAI) are among the highest in orthopaedics, a limited number of research has investigated the biomechanics of dynamic activities following-up the surgery. This doctoral thesis examined the kinematics, muscle force component, and hip contact loading in pre- and postoperative patients during the deep squat motion. Specifically, this research: 1) examined muscle strength and pelvic kinematics in asymptomatic FAI, 2) examined lower-limb kinematics and muscle activity in postoperative patients who underwent either THA or FAI correction during a deep squat task, and 3) examined muscle force contributions and hip contact forces (HCF) during dynamic motion in postoperative FAI patients. First, clinical and medical imaging evaluations classified the participants into three groups: symptomatic FAI, asymptomatic FAI (FAD – participants had the cam deformity, but no pain), and healthy controls. The FAD participants had significantly greater hip extensor strength compared to the FAI and CTRL groups, which allowed them to achieve greater pelvic mobility and squat as deep as the CTRL group. Second, at the follow-up for the FAI surgery the patients showed increased pelvic ROM during the squat, and weakness associated with hip flexion and hip flexion-with-abduction were associated with postoperative alterations. For the THA follow-up analyses, the patients using a dual- mobility (DM) prosthesis reached an anterior pelvic tilt similarly to the CTRL during the dynamic parts of the squat; however, without returning its neutral tilt at the bottom of the squat, while the single- bearing (SB) prosthesis was associated with excessive hip abduction during the squat. Third, a generic full-body musculoskeletal model (MSKM) was optimized to allow for the analysis of tasks with a high range of motion (ROM; e.g. deep squat task), which controlled muscle moment arms during the high joint flexions to avoid the model’s motor tendon units (MTU) to penetrate the bony structures and respect the anatomical via points. Simulation performed during gait demonstrated that FAI patients enhance medial-lateral hip stability postoperatively, allowing reduced dynamic forces of the muscles associated with the sagittal aspect of the gait due to a less compensatory strategy to stabilize the hip joint. Furthermore, simulations performed during deep squat showed a higher anterior pelvic tilt in postoperative FAI patients as a ‘restore to native’ mechanism once the cam-deformity was no longer present. Increased semimembranosus force was linked to higher vertical HCF and total magnitude. The outcomes of this research include findings for gait and squat analyses that provide a better understanding of the pelvic mobility and hip muscle forces in hip diseases. In silico models can improve biomechanical assessment of postoperative patients in order to quantify surgical effectiveness and support clinicians in making subject-specific case decisions. The contributions also lay on the assertion of helping us to formulate future research directions in biomechanics applied to the orthopaedics field.

Introduction: Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. I hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods: The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats using a posterior surgical approach. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa (PA) strains: a reference strain (PA14-lux) and a mutant strain that is defective in biofilm formation (flgK-lux). Infection was assessed in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI) and in vitro by quantifying bacterial loads on collected implants surface and in periprosthetic tissues as well as biofilm visualization using the Field emission scanning electron microscopy (FE-SEM). The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGaitTM system in vivo. Results: Bioluminescence detected by IVIS, was focused on the hip region, demonstrating localized-infection, with the ability of PA14-lux to persist in the model compared to flgK-lux defective in biofilm formation. This was corroborated by MRI as the PA14-lux induced relatively larger implant-related abscesses. Biofilm formation at the bone-implant-interface induced by the PA14-lux was visualized using FE-SEM versus defective-biofilm formation by flgK-lux. This could be quantitatively confirmed, by average viable-colony-count of the sonicated implants, 3.77x108CFU/ml versus 3.65x103CFU/ml for PA14-lux and flgK-lux, respectively (p=0.0025; 95%CI: -6.08x108 to -1.45x108). This difference in the ability to persist in the model was reflected significantly on the implant osseointegration with a mean intersection surface 4.1x106μm2 1.99x106 for PA14-lux versus 6.44x106μm2 2.53x106 for flgK-lux and 7.08x106μm2 1.55x106 for non-infected control (p=0.048). Conclusions: To date, the proposed in vivo biofilm-based model is the most clinically representative for GN-PJI since animals can bear weight on the implant and poor osseointegration correlates with biofilm formation. Clinical Relevance: The current model will allow for reliable testing of novel biofilm-targeting therapeutics.

A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy, to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Johannesburg 2018 / Knee osteoarthritis (OA) is the most prevalent form of OA and it is present in over 33% of adults aged 50 years and above. Patients with end-stage knee OA have poor health outcomes including severe knee pain, functional limitations and poor quality of life (QoL) with decreased physical activity (PA) and increased sedentary behaviour (SB). In spite of the cost-effectiveness of total knee arthroplasty (TKA) in improving patients’ health outcomes (as measured using patient-reported outcome measures (PROMs)), the objectively measured PA shows little or no change after surgery and SB has received very little attention following TKA. However, published studies have only been conducted in populations from high-income countries and no studies have assessed PA and SB in knee OA patients from low-middle income countries including South Africa. Furthermore, the detailed patterns by which patients with knee OA accumulate PA and SB before and after TKA have not been described. Studies have mainly focused on measuring overall PA or moderate to vigorous PA (MVPA) and/or patients’ adherence to the PA guidelines with very little attention to low intensity activities of the movement continuum (SB and light activity- LPA). Furthermore, different activity monitors have been used with very few of them capable of measuring low intensity activities. Assessing activity behaviours incidental in activities of daily living (ADL) (such as sitting, standing and walking) before and after TKA may be clinically useful as activities of older adults undergoing TKA mainly constitute these low intensity activities. With no previously published systematic review on changes in SB following TKA, the objective of the first study of this thesis was to integrate available evidence on changes in SB in patients with knee OA after a primary TKA. A systematic literature search from January 2002 to 31 October 2017 was performed across seven electronic databases, for longitudinal and cross-sectional studies published in English on objectively (through accelerometry) and/or subjectively measured changes in SB following TKA. Ten studies reporting on SB with a total of 1,028 participants were included in the review. Three studies reported changes in SB with two showing a reduction in SB and one, with high risk of bias, showing an increase in SB after TKA. Seven studies showed no change in SB following TKA. The second study of this thesis was a longitudinal design comprising of two parts (Study 2A and B). Participants wore two activity monitors (ActiGraph GT3X+ and ActivPAL) to measure PA and SB for seven consecutive days (24 hours/day) at baseline (preoperative), six weeks and six months after TKA. Therefore, the second objective (Study 2A) of this thesis was to objectively measure changes in volume and pattern of PA and SB (using ActiGraph GT3X+ accelerometer) in patients with knee OA from baseline to six months after TKA and to assess changes in PROMs following TKA. Eighty-nine patients (13 males, 76 females between 55 and 80 years of age) scheduled for primary TKA took part in the study. Physical activity and SB were measured with an ActiGraph GT3X+ accelerometer for seven consecutive days (24 hours/day) and range of motion (ROM) was measured prior to TKA, and six weeks and six months after TKA. The University of California Los Angeles (UCLA) Activity index and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess self-reported activity and physical function respectively. Of the initial 89 patients recruited, 57 completed the six months followup and 45 had valid activity data at the 6 months follow-up. The proportion of time (% of waking day) patients spent in light physical activity (LPA) increased from baseline [29.0 (26.6-31.4)%] to 6 months [34.8 (31.3-38.3)%; p=0.008]. However, time spent in moderate to vigorous PA (MVPA) did not change from baseline [median (interquartile range): 2.0 (7.8) min/day] to six months after TKA [3.4 (11.6) min/day, p>0.05]. Approximately 9%, 5% and 18% of the patients met the PA guidelines at baseline, and six weeks and six months after TKA respectively. The proportion of time (% of waking day) patients spent in SB decreased after TKA [baseline: mean (95% CI): 70.1 (67.5-72.7)%; six months: 64.0 (60.6-67.9)%; p=0.009]. The interruptions to SB increased between baseline and six months after TKA [mean (95% CI): 85.0 (80.0-90.0) to 93.0 (88.0-98.0) breaks/day, p=0.014]. There was a significant improvement in WOMAC score [median (interquartile range): 71.0 (27.0) vs. 4.0 (11.3), p<0.001], UCLA score [median (interquartile range): 2.0 (1.0) vs. 5.0 (1.0), p<0.001] as well as ROM [mean range: (0.0 - 90.0)° vs (0.0 - 110)°, p<0.05] between baseline and six months after TKA. Study 2A showed that LPA increased and SB decreased as measured using ActiGraph GT3X+. In addition, self-reported functional capacity (FC) or functional ability (as measured with PROMs) improved after TKA. The third objective (Study 2B) of this thesis was to objectively assess changes in the times spent sitting, standing and walking following TKA and to examine their associations with the changes in PROMs after TKA. The same patients in Study 2A also wore a second activity monitor, the ActivPAL (which accurately measures low intensity activities and posture) for the same periods of time as described in Study 2A above. Patients spent significantly more of their waking wear time walking at six months after TKA (mean% (95% CI): 10.8% (9.4-12.1)), than preoperatively (mean% (95% CI): 8.3% (7.7-10.0)), p=0.039), however, the percentage of daily time spent standing did not change at six months after TKA (mean% (95% CI): 34.2% (29.8-38.6)) compared to percentage time preoperatively (mean% (95% CI): 32.4% (28.6-35.5)), p=0.530). Patients decreased their average daily time spent sitting from preoperative to six months after TKA by 33.7 mins/day (95% CI: -18.9 – 106.3, p=0.099). Patients took significantly more steps per day at six months after TKA [mean (95% CI: 3670 (2886-4020)] steps/day compared to preoperatively 2570 (2366-3189) steps/day, p<0.001. Participants also increased their cadence (steps/min) six months after surgery [mean (95% CI): 33 (31-34) vs. 38 (33-39), p=0.004]. There were no associations between objectively measured changes in the time spent sitting, standing and walking and changes in PROMs (p>0.05). The studies presented in this thesis have novel aspects that extend the body of knowledge on activity behaviours of patients with knee OA undergoing TKA. The studies in this thesis report the first systematic review on changes in SB of knee OA patients following TKA. This thesis is the first to objectively measure the detailed patterns of PA and SB in patients with knee OA undergoing TKA from a low-middle income country (South Africa). Furthermore, this thesis is also the first to use two accelerometers to generate detailed activity behaviour in patients with knee OA undergoing TKA. Lastly, this thesis is the first to assess the association between changes in times spent sitting, standing and walking in relation to changes in health outcomes in knee OA patients after TKA. In conclusion, the systematic review showed that SB has been superficially described and there is insufficient evidence to suggest that time spent in SB decreases following TKA. Majority of the studies reported no change in SB after TKA. The longitudinal study showed that, following TKA, there was a decrease in the overall time spent in SB and an increase in the number of breaks in SB that appeared to be replaced by LPA. Participants’ volume and average daily cadence increased following TKA. In addition, participants decreased their time spent sitting by over half an hour at six months after TKA. However, there were no associations between changes in the times spent sitting, standing and walking and changes in measures of participants’ health outcomes (PROMs) following TKA. Both objective and subjective measures should be used to accurately assess improvements in patients’ health outcomes following TKA. This comprehensive analysis of detailed daily activity behaviours can be used to employ feasible interventions for increasing the duration of LPA (standing and walking) and decreasing sedentary time (sitting/lying) to improve quality of life and overall health following TKA. / XL2019