The potential of sheep in preclinical models for bone infection research - A systematic review.

Background: Reliable animal models are critical for preclinical research and should closely mimic the disease. With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical characteristics to humans. Their use in bone research is established, however their use in bone infection research is limited. This systematic review will summarise the key features of the available bone infection models using sheep, providing a reference for further development, validation, and application. Method: This systematic review was designed according to the PRISMA guidelines and registered with PROSPERO. Quality was assessed using SYRICLE's risk of bias tool adapted for animal studies. PubMed, MEDLINE, Web of Science and EMBASE were searched until March 2022.1921 articles were screened by two independent reviewers, and 25 were included for analysis. Results: Models have been developed in nine different breeds. Staphylococcus aureus was used in the majority of models, typically inoculating 108 colony forming units in tibial or femoral cortical defects. Infection was established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most studies used both radiological and microbiological analyses to confirm osteomyelitis. Conclusions: There is convincing evidence supporting the use of sheep in bone infection models of clinical disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the success for translating in vivo results to successful therapies. The Translational potential of this article: In the realm of preclinical research, the translation to viable clinical therapies is often perilous, and the quest for reliable and representative animal models remains paramount. This systematic review accentuates the largely untapped potential of sheep as large animal models, especially in bone infection research. The anatomical and biomechanical parallels between sheep and human bone structures position sheep as an invaluable asset for studying osteomyelitis and periprosthetic joint infection. This comprehensive exploration of the literature demonstrates the robustness and translational promise of these models. Furthermore, this article underscores the potential applicability for sheep in developing effective therapeutic strategies for human bone infections.

Large hospital variation in the risk of dislocation after primary total hip arthroplasty for primary osteoarthritis: 31,105 patients in 59 hospitals from the Danish Hip Arthroplasty Register.

BACKGROUND AND PURPOSE: The risk of dislocation after primary total hip arthroplasty (THA) is affected by several factors, which increases the possibility of substantial differences among hospitals. We compared cumulative incidences of dislocation between regions and hospitals after primary THA surgery in osteoarthritis (OA) patients. PATIENTS AND METHODS: From the Danish Hip Arthroplasty Register, we included 31,105 THAs performed from 2010 to 2014 with 2 years' follow-up. Dislocations treated by closed reduction were identified in the Danish National Patient Register combined with patient file review. The results are presented as 2-year cumulative incidence on national, regional, and hospital level as proportions with 95% confidence intervals (CI) and as adjusted odds ratios (OR) analyzed by multiple logistic regression. RESULTS: 1,861 dislocations in 1,079 THAs were identified from 59 orthopedic departments. The 2-year cumulative incidence ranged from 2.2% to 4.3% between the 5 regions in Denmark. Hospital variation was 0-12%. For hospitals with a 5-year volume of more than 100 procedures, the incidence was 0.9-7.4%. Using the highest volume hospital as the reference, ORs for dislocation for the remaining hospitals were between 0.3 (CI 0.1-0.6) and 2.7 (1.9-4.0) after adjusting for age, sex, head size, and fixation method. Low-volume hospitals showed a higher dislocation risk than high-volume units with an adjusted OR of 1.2 (1.1-1.4). INTERPRETATION: We found substantial variation in the incidence of dislocation between hospitals within Denmark, which can be explained by a combination of patient-, component-, and surgery-related factors. There is a need for continuous monitoring of THA dislocation on regional and hospital levels to reduce overall and local dislocation risk for future patients.

Patient-reported outcome after dislocation of primary total hip arthroplasties: a cross-sectional study derived from the Danish Hip Arthroplasty Register.

Background and purpose - Knowledge regarding patient-reported outcomes (PROs) after dislocation and closed reduction is lacking. We report health- and hip-related quality of life (QoL) after dislocation, following primary total hip arthroplasty (THA). Patients and methods - We conducted a crosssectional study with patients registered in the Danish Hip Arthroplasty Register from 2010 to 2014. Dislocations were captured based on diagnosis/procedure codes and patient file reviews. Patients with dislocation were matched 1:2, according to age, sex, date, and hospital of primary surgery, to patients without dislocation. 2 PRO questionnaires were applied (EQ-5D, HOOS). Results - We identified 1,010 living patients with dislocation. Mean follow-up was 7.2 years from index surgery and 4.9 years (range 0.6-9.7) from the latest dislocation. Patients without dislocation reported a higher EQ VAS score of 76 (95% CI 75-77) compared with 68 (CI 66-70) for the dislocation group. The EQ-5D-5L mean index score was 0.89 (CI 0.88-0.90) for the control group, compared with 0.78 (CI 0.76-0.80) for the cases with dislocation without revision. Patients with dislocation reported a lower HOOSQoL domain score of 63 (CI 60-65), compared with 83 (CI 82-84) for the control group. Even 5 years after the latest dislocation, the HOOS-QoL score remained low, at 66 (CI 62-69). The other HOOS domains were consistently 8-10 points worse after dislocation. Interpretation - Both health- and hip-related QoL were markedly and persistently reduced among dislocation patients compared with those in controls, for several years. Therefore, the avoidance of the initial dislocation episode is important because the THA does not appear to achieve the full relieving potential.

Risk Factors for Dislocation and Re-revision After First-Time Revision Total Hip Arthroplasty due to Recurrent Dislocation - A Study From the Danish Hip Arthroplasty Register.

BACKGROUND: Persistent instability after hip revision is a serious problem. Our aim was to analyze surgical and patient-related risk factors for both a new dislocation and re-revision after first-time hip revision due to dislocation. METHODS: We included patients with a primary THA due to osteoarthritis and a first-time revision due to dislocation registered in the Danish Hip Arthroplasty Register (DHR) from 1996 to 2016. We identified dislocations in the Danish National Patient Register and re-revisions in the DHR. Risk factors were analyzed by a multivariable regression analysis adjusting for the competing risk of death. Results are presented as subdistribution hazard ratios (sHR). RESULTS: We identified 1678 first-time revisions due to dislocation. Of these, 22.4% had a new dislocation. 19.8% were re-revised for any reason. With new dislocations treated by closed reduction as the endpoint, the sHR was 0.36 (95% CI, 0.27-0.48) for those who had a constrained liner (CL) during revision and 0.21 (0.08-0.58) for dual mobility cups (DMC), thereby lowering the risk of dislocation compared to regular liners. Changing only the head/liner increased the risk of dislocation (sHR = 2.65; 2.05-3.42) compared to full cup revisions. The protective effect of CLs and DMCs on dislocations vanished when re-revisions became the endpoint. The head/liner exchange was still found inferior compared to cup revision (sHR = 1.73; 1.34-2.23). CONCLUSION: Patients revised with DMCs and CLs were associated with a lower risk of dislocation after a first-time revision but not re-revision, whereas only changing the head/liner was associated with a higher risk of dislocation and re-revision of any cause compared to cup revision.

"True" Cumulative Incidence of and Risk Factors for Hip Dislocation within 2 Years After Primary Total Hip Arthroplasty Due to Osteoarthritis: A Nationwide Population-Based Study from the Danish Hip Arthroplasty Register.

BACKGROUND: Hip dislocation is one of the leading indications for revision of total hip arthroplasty (THA) implants, and the extent of this complication is often measured by the number of revisions. The exact incidence of dislocation can be difficult to establish as closed reductions may not be captured in available registers. The purpose of this study was to identify the "true" cumulative incidence of hip dislocation (revisions and closed reductions) after primary THA, and the secondary aim was to identify risk factors for dislocation. METHODS: From the Danish Hip Arthroplasty Register, we identified 31,105 primary THAs indicated by primary osteoarthritis that had been performed from 2010 to 2014 and had 2 years of follow-up. Dislocations were identified through extraction from the Danish National Patient Register. Matching diagnosis and procedure codes were deemed correct while non-matching codes were reviewed through a comprehensive, nationwide review of patient files. Risk factors were analyzed with multiple logistic regression analysis and presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Our review of patient files identified 1,861 dislocations in 1,079 THAs, which corresponds to a 2-year cumulative incidence of 3.5% (CI = 3.3% to 3.7%). This was a 50% increase compared with the correctly coded dislocations captured by administrative register data only. Patients who were <65 years of age had a lower dislocation risk (OR = 0.70; CI = 0.59 to 0.83) and those who were >75 years of age had a higher risk (OR = 1.32; CI = 1.14 to 1.52) compared with those who were 65 to 75. Male sex (OR = 0.86; CI = 0.75 to 0.98), cemented fixation (OR = 0.71; CI = 0.58 to 0.87), and lateral approach (OR = 0.28; CI = 0.16 to 0.49) were all associated with a lower risk. A head size of 32 mm was associated with a higher risk of dislocation (OR = 1.27; CI = 1.10 to 1.46) than 36-mm heads, whereas dual-mobility cups had a reduced risk (OR = 0.13; CI = 0.05 to 0.36). CONCLUSIONS: We found the "true" cumulative incidence of dislocations within 2 years after primary THAs performed between 2010 and 2014 in Denmark to be 3.5%. Age, sex, American Society of Anesthesiologists (ASA) score, head size and type, fixation method, and surgical approach were independent significant factors for dislocation. Comprehensive search algorithms are needed in order to identify all dislocations so that this complication can be accurately reported in national registers.

Empowerment of whom? The gap between what the system provides and patient needs in hip fracture management: A healthcare professionals' lifeworld perspective.

AIMS AND OBJECTIVES: To use a Habermasian lifeworld theoretical perspective to illuminate a treatment gap for hip fracture patients in a Danish university hospital to guide future healthcare services. BACKGROUND: Most healthcare systems focus on systematised guidelines to help reduce hospital length of stay in response to increasing demand because of the ageing of the global population. For patients with hip fractures, a previous study demonstrated that there is a lack of patient empowerment and a gap between patients' needs and wishes and what was provided by the healthcare system. DESIGN: In this follow-up study, the previous findings were introduced to a mixed group of health professionals (HPs) who participated in focus group discussions (n = 3, with a total of 18 HPs). METHODS: Data were analysed using qualitative content analysis. By analysing the discourse of the discussions using Habermas' perspective, the lack of patient-empowerment was illuminated and facilitated, describing it in terms of the gap it creates in communicative actions between HPs and patients. RESULTS: Information and education of patients in systematised pathways, such as those for patients with hip fractures, are dominated by a biomedical discourse. Patients are overwhelmed by the psycho-social implications of the hip fracture, leaving them in a shock-like state of mind. CONCLUSION: Empowerment of patients should involve empowerment of HPs by providing them with skills to support patients in a shock-like state of mind. There is also a need to provide HPs with a more individually targeted means of informing and educating patients.

Rationale and methods of an observational study to support the design of a nationwide surgical registry: the MIDAS study.

BACKGROUND Surgical registries are becoming increasingly popular. In addition, Swiss legislation requires data on therapeutic outcome quality. The Swiss Association of Surgeons (Schweizerische Gesellschaft Chirurgie, SGC-SCC) has already agreed on a first minimum data set. However, in the long run the scope and content of the registry should be evidence-based and not only accepted by professional stakeholders. The MIDAS study aims at providing such evidence for the example population of patients undergoing emergency or elective hip surgery. Five relevant aspects are considered: (1) choice of instruments for assessing health related quality of life (HRQoL); (2) optimal time-point for assessment; (3) use of proxy assessments; (4) choice of pre-surgery risk factors; and (5) assessment of peri- and postoperative variables. METHODS MIDAS is a longitudinal observational multicentre study. All patients suffering from a femoral neck fracture or from arthritis of the hip joint with an indication for prosthetic joint replacement surgery will be offered participation. The study is based on a combination of routine data from clinical standard practice with specifically documented data to be reported by the treating clinician and data to be collected in cooperation with the patient ­ in particular patient-reported outcome measures (PROMs). The latter include the Health Utility Index Mark 3 (HUI3) and Euro-Qol-5D (EQ-5D) as generic instruments, Hip Disability and Osteoarthritis Outcome Score (HOOS) as a disease specific instrument for the assessment of HRQoL, and two performance-based functional tests. Data will be collected at baseline, during hospitalisation/at discharge and at three routine follow-up visits. All patients will be asked to name a person for assessing proxy-perceived HRQoL. DISCUSSION To the best of our knowledge, this is the first study explicitly addressing questions about the design of a national surgical registry in an empirical manner. The study aims at providing a scientific base for decisions regarding scope and content of a potential national Swiss surgical registry. We designed a pragmatic study to envision data collection in a national registry with the option of specifying isolated research questions of interest. One focus of the study is the use of PROMs, and we hope that our study and their results will inspire also other surgical registries to take this important step forward. Trial registration Registered at the "Deutsches Register Klinischer Studien (DRKS)", the German Clinical Trials Registry, since this registry meets the scope and methodology of the proposed study. Registration no.: DRKS00012991