Yes / Objective To determine whether an immediate reporting service for musculoskeletal trauma reduces interpretation errors and positively impacts on patient referral pathways. Methods A pragmatic multicentre randomised controlled trial was undertaken. 1502 patients were recruited and randomly assigned to an immediate or delayed reporting arm and treated according to group assignment. Assessment was made of concordance in image interpretation between emergency department (ED) clinicians and radiology; discharge and referral pathways; and patient journey times. Results 1688 radiographic examinations were performed (1502 patients). 91 discordant interpretations were identified (n=91/1688; 5.4%) with a greater number of discordant interpretations noted in the delayed reporting arm (n=67/849, 7.9%). In the immediate reporting arm, the availability of a report reduced, but did not eliminate, discordance in interpretation (n=24/839, 2.9%). No significant difference in number of patients discharged, referred to hospital clinics or admitted was identified. However, patient ED recalls were significantly reduced (z=2.66; p=0.008) in the immediate reporting arm, as were the number of short-term inpatient bed days (5 days or less) (z=3.636; p<0.001). Patient journey time from ED arrival to discharge or admission was equivalent (z=0.79, p=0.432). Conclusion Immediate reporting significantly reduced ED interpretive errors and prevented errors that would require patient recall. However, immediate reporting did not eliminate ED interpretative errors or change the number of patients discharged, referred to hospital clinics or admitted overall. Advances in knowledge This is the first study to consider the wider impact of immediate reporting on the ED patient pathway as a whole and hospital resource usage.

Musculoskeletal trauma including fractures, represents a significant burden of disease for Low- and Middle-Income Countries (LMICs). Within LMICs, women possess reduced agency to make health care decisions and represent a vulnerable population. In this thesis, I aimed to characterize priority fractures among women within LMICs, and investigated whether women were delayed in hospital admission following an orthopaedic trauma. In Chapter 1, I introduce and review the existing literature on injury burden, health care deficiencies, and gender inequities within LMICs. In Chapter 2, we analyzed regional distributions of fracture burdens across 9,934 female orthopaedic trauma patients across 17 LMICs. Half of our study patients were ≥ 60 years old. We determined that the major burden of orthopaedic trauma among women within LMICs were fractures among the elderly. Fracture burden in Africa was notably different. A majority of patients were between the ages 18-59, and common fractures included tibia/fibula and femur fractures. In Chapter 3, we analyzed 26,910 orthopaedic trauma patients across 17 LMICs to determine whether women were delayed in hospital admission by >24 hours. After controlling for confounds, sex was not a significant predictor of delay. We found that instead, the severity and type of fracture influenced the delay of patient’s hospital admission. Closed fractures, falling-related injuries, pelvic, spine and hip fractures were associated with increasing delay. Irrespective of sex and region, inter-hospital referrals accounted for nearly half of the reasons patients were delayed. These two chapters highlight regional trends in orthopaedic burden sustained by women, pointing to the high frequency of fragility fractures. In addition, this thesis identifies critical gaps within LMICs’ health care systems infrastructure, demonstrating the need for improved hospital referral systems and ambulatory services. This analysis will enable policymakers, and future researchers to target interventions to address the rising global burden of injuries especially among women. / Thesis / Master of Science (MSc) / Fractures represent life-threatening injuries within Low- and Middle-Income Countries (LMICs), and globally are a top-ten leading cause of death and disability. Within LMICs, due to gender inequalities, women may be restricted from receiving hospital care following an injury. We investigated the most common types of fractures in women within LMICs and determined that women most frequently experienced fractures due to old age. We further examined whether women were delayed in reaching a hospital after sustaining a fracture, and found that sex did not significantly play a role in determining delay. Instead, injury associated factors, such as the type and severity of the fracture influenced whether a patient was delayed. In addition, transferring patients between hospitals was the most common reason for delay. As a result, policymakers in LMICs should explore strategies to treat the high burden of fractures in the elderly and improve communication between hospitals to reduce delays.

Με τον όρο «Έκτοπη Οστεοποίηση» περιγράφεται ο σχηματισμός οστού σε σημεία που υπό φυσιολογικές συνθήκες δεν υφίσταται. Τα σημεία αυτά μπορεί να είναι μύες, τένοντες ή σύνδεσμοι και γενικότερα μεσεγχυματικού τύπου μαλακά μόρια, κυρίως γύρω από τις μεγαλύτερες αρθρώσεις. Η επίκτητη μορφή της νόσου, που είναι και η πιο κοινή, εμφανίζεται μετά από μυοσκελετικούς τραυματισμούς, κακώσεις του νωτιαίου μυελού και του κεντρικού νευρικού συστήματος γενικότερα, αλλά και σε περιπτώσεις σοβαρών εγκαυμάτων. Η παθοφυσιολογία της έκτοπης οστεοποίησης παραμένει άγνωστη, αυτό που γνωρίζουμε με βεβαιότητα είναι ότι για τον σχηματισμό της απαιτούνται τρείς βασικές προϋποθέσεις που είναι α) τα οστεοπρογονικά κύτταρα, β) οι κατάλληλοι επαγωγικοί παράγοντες και γ) το ευνοϊκό οστεοεπαγωγικό περιβάλλον. Στην παρούσα εργασία με την χρήση κυτταρομετρίας ροής, δοκιμασιών με ηλεκτροχημειοφωταύγεια, Elisa και ανοσοπροσδιορισμού με χρήση Cytometric Bead Array προσδιορίσαμε τις συγκεντρώσεις των total procollagen type 1 amino-terminal propeptide (TP1NP), osteoprotegerin (OPG), β-isomerized C-terminal telopeptides (β- Crosslaps), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), N-MID osteocalcin, S100 και των κυτταροκινών IL-2, IL-4, IL-6, IL-10, INF-γ και TNF-a στον ορό ασθενών και υγιών μαρτύρων. Επιπλέον, στο ολικό αίμα προσδιορίσαμε τον πληθυσμό των θετικών στην οστεοκαλσίνη κυττάρων. Όλα τα προς μελέτη μόρια είχαν άμεση ή έμμεση σχέση με την οστική ανακατασκευή και τις φλεγμονώδεις αντιδράσεις. Συνολικά μελετήθηκαν 55 ασθενείς από τους οποίους ελήφθησαν δείγματα καθόλη την διάρκεια νοσηλείας τους. Οι ασθενείς μελετήθηκαν με βάση το είδος του τραύματος, την εμφάνιση ή όχι έκτοπης οστεοποίησης και την έκβαση της κατάστασης τους. Επιπλέον, οι επιμέρους ομάδες ασθενών μελετήθηκαν συναρτήσει του χρόνου. Τα αποτελέσματα μας έδειξαν ότι στο σύνολο των ασθενών παρατηρήθηκαν στατιστικά μειωμένα επίπεδα β- crosslaps, N-MID osteocalcin, sRANKL και S100 συγκριτικά με τους υγιείς μάρτυρες. Αντίθετα, τα επίπεδα των TP1NP, των θετικών στην οστεοκαλσίνη κυττάρων, της OPG, της INF-γ και της IL-6 ήταν στατιστικά σημαντικά αυξημένα. Επιπλέον, στατιστικά σημαντικά αυξημένα παρατηρήθηκαν τα επίπεδα του S100 στους ασθενείς που είχαν υποστεί κρανιοεγκεφαλικές κακώσεις κατά το πρώτο εικοσιτετράωρο μετά την επαγωγή της κάκωσης. Στατιστικά σημαντικά αυξημένο επίσης παρατηρήθηκε και στην ομάδα των ασθενών με κακή έκβαση συγκριτικά με τους υγιείς δότες. Στην ίδια ομάδα ασθενών παρατηρήθηκε μια γενικευμένη αύξηση των επιπέδων των κυτταροκινών που φαίνεται να σχετίζεται άμεσα με την κακή έκβαση της κατάστασης τους. Πιο συγκεκριμένα η αύξηση αυτή ήταν στατιστικώς σημαντική για τις IL-4, INF-γ και TNF-α. / Heterotopic ossification (HO) is the presence of bone in soft tissue where normally does not exist. The acquired form, which is also the most common, develops after musculoskeletal trauma, spinal cord injury or central nervous system injury and severe burns. Pathophysiology of OH still remains unclear, what we know is that the formation of ectopic bone requires three entities which are a) osteogenic precursor cells, b) inducing agents and c) an appropriate environment. In the present study using either flow cytometry, Elisa, electrochemiluminescence immunoassays or cytometric bead array assays we determined the concentrations of the osteoblast progenitors: osteocalcin positive cells in peripheral blood and the serum concentrations of total procollagen type 1 amino-terminal propeptide (TP1NP), osteoprotegerin (OPG), β-isomerized C-terminal telopeptides (β- Crosslaps), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), N-MID osteocalcin, S100 and the cytokines IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-a. All measured molecules participate directly or indirectly in bone formation and metabolism and in inflammation. Our 55 patients were divided and studied in 3 different ways, regarding the kind of their injury, their outcome and the formation of HO. They were also monitored in course of time. Among our most interesting results is that patients had significantly lower levels of β- crosslaps, N-MID osteocalcin, sRANKL and S100 compared to healthy donors. On the other hand, levels of TP1NP, osteocalcin positive cells, OPG, INF-γ and IL-6 were significantly higher. S100 is significantly increased during the first 24 hours in patients who have sustained traumatic brain injury. In addition, S100 was significantly increased in patients with poor outcome compared to healthy donors. Furthermore, patients with poor outcome seem to develop a cytokine storm which is of great importance for their outcome. All measured cytokine levels were increased compared to patients with good outcome. Especially for IL-4, INF-γ, TNF-α this increase was statistically significant.