Intra-articular glucocorticoid injection therapy is frequently used to relieve symptoms of arthritis, but there is considerable variation in injection routines among physicians. One issue of debate concerns the importance of synovial fluid aspiration during the injection procedure. In the present randomised controlled study of patients with rheumatoid arthritis (RA), a significantly reduced risk for arthritis relapse was observed when arthrocentesis was included in the intra-articular injection procedure of the knee. Furthermore, there is no consensus about the post-injection regimes. Previous studies have shown beneficial effects of post-injection rest of the knee, but also injection routines for other joints often include such recommendations. The present randomised controlled trial showed that 48-hour rest in elastic orthosis after intra-articular injection in the wrist did not improve the outcome. Thus, the effect of post-injection rest varies between different joints. The improved treatment result of post-injection rest of the knee is supposed to be caused by retarded steroid resorption from the joint. In order examine the metabolic effects in cartilage, bone and the hypothalamic-piuitary-adrenal (HPA)-axis, resting and mobile RA patients were studied after intra-articular knee injections. Serum levels of the injected glucocorticoid, triamcinolone hexacetonide (THA), were analysed, as well as cartilage oligomeric matrix protein (COMP) as a marker of cartilage turnover, osteocalcin for bone formation and deoxypyridinoline for bone resorption. The HPA-axis was assessed using serum levels of cortisol and adrenocorticotropine hormone. The result showed a short term and reversible suppression of the HPA-axis and bone formation, whereas bone resorption was unaffected. No differences between mobile and resting patients were observed. In both groups reduction of COMP levels were seen, but these were significantly more pronounced in resting patients, suggesting a cartilage-protective effect. The THA levels increased similarly in both groups, indicating that rest did not affect glucocorticoid resorption. Consequently, another explanation for the beneficial effects of postinjection rest of knee synovitis should be considered. In the present material the incidence of infectious complications of intra-articular treatment was less than 1/12,000 injections. The findings in this thesis can be applied in the clinical practice and should be considered when new guidelines for intra-articular glucocorticoid therapy are created.

Abstract Healthcare-associated infections (HAI) are infections acquired during treatment in a healthcare facility. The most common infections are pneumonias, surgical site infections (SSIs) and urinary tract infections (UTIs). HAIs burden the healthcare system by increasing patient days, the use of antibiotics, examinations, and thus the costs of care. The occurrence of HAIs can be used to evaluate the quality of care and to make comparisons between institutions. The purpose of this dissertation was to evaluate the burden of HAIs in the primary and tertiary healthcare wards and the costs of procedure-related prosthetic joint infections (PJIs). The first part of this dissertation evaluated the prevalence of HAIs in the wards of primary healthcare in the Oulu University Hospital (OUH) district with two point prevalence studies (one-day sampling) conducted in 2006 and in 2017. In 2006, the study comprised 27 healthcare centres with 44 wards and 1,294 patients. HAIs were found in 9.3% of the patients. The most common infections were UTIs, skin and soft tissue infections and lower respiratory tract infections (LRTIs). In 2017, there were 20 healthcare centres with 34 wards and 764 patients; 9.4% of the patients had a HAI. The most common HAIs were pneumonias, SSIs and LRTIs. In the second part, we evaluated the incidence of HAIs in the OUH with a computer-based electronic infection surveillance program. The study covered 15 adult wards with a total of 353 beds. The overall incidence of HAIs during the six-year study period was 4.5% of discharged patients. The most common infections were SSIs, pneumonias and UTIs. The surveillance carried out in this way required a total of one person's workload per year. The third part evaluated hospital costs of procedure-related PJIs. The study population consisted of all total knee and hip arthroplasties performed in the OUH from 2013 to 2015: 1,768 patients with 42 PJIs. A PJI tripled the cost of a procedure compared to an arthroplasty without an infection (€25,100 vs. €7,200). Two-stage revision caused three times more costs than debridement, antibiotics and implant retention treatment (DAIR) (€53,400 vs. €18,500). HAIs are common in the wards of primary and tertiary healthcare in the OUH district. Electronic HAI monitoring is feasible but requires relatively large employer resources. Postoperative PJI triples the cost of the procedure. / Tiivistelmä Sairaalainfektio (SI) on infektio, jonka potilas saa ollessaan hoidossa laitoksessa. Yleisimpiä SI:ita ovat leikkausalueen infektio, keuhkokuume ja virtsatieinfektio (VTI). SI:t kuormittavat terveydenhoitoa lisäämällä hoitopäiviä, antibioottien käyttöä, tutkimuksia ja näin myös hoidon kustannuksia. SI:iden määrää voidaan käyttää hoidon laadun mittarina sekä sairaaloiden väliseen vertailuun. Tämän väitöskirjan tarkoituksena oli arvioida SI:iden määrää Pohjois-Pohjanmaan sairaanhoitopiirin (PPSHP) terveyskeskusten ja Oulun yliopistosairaalan (OYS) vuodeosastoilla sekä selvittää tekonivelleikkauksen jälkeisen tekonivelinfektion (TI) aiheuttamia sairaalakustannuksia. Väitöskirjan ensimmäisessä osatyössä selvitettiin SI:iden esiintyvyyttä PPSHP:n terveyskeskusten vuodeosastoilla pisteprevalenssilla eli yhden päivän otannalla vuosina 2006 ja 2017. Vuoden 2006 tutkimuksessa oli 27 terveyskeskusta, joissa oli 44 vuodeosastoa ja yhteensä 1 294 potilasta. SI todettiin 9,3 %:lla potilaista. Yleisimpiä olivat VTI:t, pehmytkudosinfektiot ja alahengitystieinfektiot. Vuonna 2017 tutkimuksessa oli 20 terveyskeskusta, 34 vuodeosastoa ja 764 potilasta. Tällöin SI todettiin 9,4 %:lla. Yleisimmät infektiot olivat keuhkokuume, leikkausalueen infektio ja alahengitystieinfektio. Toisessa osatyössä selvitettiin OYS:n SI:iden ilmaantuvuutta kuuden vuoden ajan jatkuvan infektioseurannan mahdollistavan tietokoneohjelman avulla. Tutkimuksessa seurattiin 15:ttä aikuisvuodeosastoa, joissa oli yhteensä 353 potilaspaikkaa. SI todettiin 4,5 %:ssa hoitojaksoista. Seuranta vaati yhteenlaskettuna noin yhden hoitajan työpanoksen vuodessa. Väitöskirjan kolmannessa osatyössä selvitettiin vuosina 2013–2015 OYS:ssa tehtyjen tekonivelleikkausten jälkeisten TI:iden sairaalakustannuksia. Tutkimuksessa oli 1 768 tekonivelleikkausta, joista 42 infektoitui. Infektoitumattoman tekonivelleikkauksen sairaalakustannukset olivat keskimäärin 7 200 € ja TI:iden 25 100 €. Hoitomenetelmänä kaksivaiheisen revision eli tekonivelen vaihtohoidon hinta oli kolminkertainen tekonivelen säilyttävään hoitoon verrattuna (53 400 € vs. 18 500 €). SI:t ovat yleisiä PPSHP:n alueella sekä terveyskeskusten että OYS:n vuodeosastoilla. SI:iden seurantaohjelma soveltuu infektioseurantaan, mutta se vaatii kohtalaisesti henkilökuntaresurssia. Leikkauksen jälkeinen TI kolminkertaistaa tekonivelleikkauksen sairaalakustannukset.

L’objectif de ces travaux de thèse a été de contribuer à la compréhension de la physiopathologie des infections sur matériel ostéo-articulaire (IMOA) à C. acnes. Dans un premier temps, nous avons typé par MLST 108 isolats de C. acnes responsables de 34 cas d’IMOAs monomicrobiennes et corrélé les résultats de typage aux données clinico-biologiques. Nous avons ainsi montré que les IMOAs à C. acnes correspondent à 2 entités cliniques : i) les cas « homotypiques » qui sont des vraies infections dues à un clone de C. acnes responsable d’une réponse inflammatoire de l’hôte ii) les cas hétérotypiques qui sont une colonisation ou contamination itérative du matériel ostéo-articulaire en l’absence de réponse inflammatoire de l’hôte. Ces données de typage ont souligné les limites de la définition microbiologique actuelle d’une IMOA quand il s’agit de C. acnes et la nécessité d’intégrer un outil moléculaire fiable dans le diagnostic microbiologique de routine de ces infections. Nous avons par conséquent évalué la technique SLST développée pour un typage rapide et optimal de C. acnes en routine. Le pouvoir discriminant de cette technique était insuffisant suggérant que seule la mise en place du NGS en temps réel dans les laboratoires de microbiologie pourrait répondre au besoin de typage moléculaire pour améliorer le diagnostic microbiologique de ces infections.Nos résultats de typage ont montré que la clonalité de l’infection plutôt que le complexe clonal (CC) est le principal facteur déterminant du processus physiopathologique et inflammatoire de l’IMOA à C. acnes. Cette conclusion est concordante avec les résultats que nous avons obtenus dans un modèle in vitro d’infection de macrophages THP-1 par C. acnes. Grâce à ce modèle, nous avons pu montrer que la réponse inflammatoire in vitro de nos isolats est souche –et non CC– dépendante. De plus, les réponses inflammatoires in vitro et in vivo n’étaient pas corrélées. Ceci souligne les limites des modèles in vitro dans l’étude de la physiopathologie des IMOAs à C. acnes dans lesquels l’adaptation de la bactérie à l’hôte est complètement négligée lors de l’étude de la réponse immune. Dans la dernière partie de ce travail, nous avons confirmé l’importance de l’environnement dans le conditionnement du comportement de la bactérie. Nous avons mené une étude comparative des caractéristiques culturales ex vivo et ex vitro de nos isolats de C. acnes. Nous avons montré l’impact du CC et des conditions environnementales, par extension la pression que peut exercer l’hôte, sur le profil cultural de C. acnes. En conclusion, nos travaux montrent qu’une approche multifactorielle, intégrant à la fois la génomique et la réponse de l’hôte, est nécessaire pour comprendre la physiopathologie des IMOAs à C. acnes. / The aim of this thesis was to contribute to the understanding of the physiopathology of C. acnes orthopedic-device related infections (ODRI). Firstly, we typed by MLST 108 C. acnes isolates responsible for 34 cases of monomicrobial ODRIs and correlated typing results with bio-clinical data. We have shown that C. acnes ODRIs correspond to two clinical entities: i) "homotypic" cases corresponding to true infections with a single pathogenic clone of C. acnes eliciting an inflammatory response ii) heterotypic cases corresponding to colonization or iterative contamination of the implant without systemic inflammatory response. These typing data highlighted the limitations of the current microbiological definition of ODRI when it comes to C. acnes and the need to incorporate a reliable molecular tool into the routine microbiological diagnosis of these infections. We therefore evaluated the SLST technique developed for a rapid and optimal typing of C. acnes. The discriminating power of this technique was insufficient suggesting that only the establishment of real-time NGS in microbiology laboratories could improve the microbiological diagnosis. Our typing results showed that the clonal status of the infection and not CC is the main determining factor in the physiopathological and inflammatory process of C. acnes ODRI. This conclusion is consistent with our results obtained on an in vitro model of a macrophage THP-1 infection. Using this model, we have shown that the in vitro inflammatory response of our isolates is strain- and non-CC-dependent. In addition, the in vitro and in vivo inflammatory responses were not correlated. This underscores the limitations of in vitro models in the study of C. acnes ODRIs in which the adaptation of the bacteria to the host is completely neglected during the study of the immune response. Finally, we confirmed the importance of the environment in the conditioning of the behavior of the bacterium. We conducted a comparative study of the ex vivo and ex vitro growth characteristics of our C.acnes isolates. We have shown the impact of CC and environmental conditions, by extension the pressure that can exert the host, on the cultural profile of C. acnes. In conclusion, our work shows that a multifactorial approach, integrating both genomics and host response, is needed to understand the physiopathology of C. acnes ODRI.

Polymethylmethacrylate (PMMA) removal during septic total joint arthroplasty revision is associated with a high fracture and perforation risk. Ultrasonic cement removal is considered a bone-preserving technique. Currently, there is still a lack of sound data on efficacy as it is difficult to detect smaller residues with reasonable technical effort. However, incomplete removal is associated with the risk of biofilm coverage of the residue. Therefore, the study aimed to investigate the efficiency of ultrasonic-based PMMA removal in a human cadaver model. The femoral components of a total hip and a total knee prosthesis were implanted in two cadaver femoral canals by 3rd generation cement fixation technique. Implants were then removed. Cement mantle extraction was performed with the OSCAR-3-System ultrasonic system (Orthofix®). Quantitative analysis of cement residues was carried out with dual-energy and microcomputer tomography. With a 20 µm resolution, in vitro microcomputer tomography visualized tiniest PMMA residues. For clinical use, dual-energy computer tomography tissue decomposition with 0.75 mm resolution is suitable. With ultrasound, more than 99% of PMMA was removed. Seven hundred thirty-four residues with a mean volume of 0.40 ± 4.95 mm3 were identified with only 4 exceeding 1 cm in length in at least one axis. Ultrasonic cement removal of PMMA was almost complete and can therefore be considered a highly effective technique. For the first time, PMMA residues in the sub-millimetre range were detected by computer tomography. Clinical implications of the small remaining PMMA fraction on the eradication rate of periprosthetic joint infection warrants further investigations.