This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. ... more This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. To my wonderful and long-suffering girlfriend Mary (whom I convinced to marry me by the end of my studies): thank you for supporting me throughout this endeavour.
Journal of Bone and Joint Surgery-british Volume, 2013
Introduction Fracture non-union is a devastating cause of patient morbidity. The cost of NU treat... more Introduction Fracture non-union is a devastating cause of patient morbidity. The cost of NU treatment ranges from £7,000 to £79,000. With an estimated 11,700 cases in the UK pa the financial implications are huge, potentially costing several hundreds of million of pounds annually. Successful outcome in the management of non-union is based upon correctly identifying the underlying cause(s) and addressing them appropriately. Aim The aim of this study was to assess the causative factors in non-union in order to optimize the management of non-union. The causes of NU were categorized into 4 groups (infection, dead bone/gap, host factors, mechanical). Method 100 consecutive patients who had surgery for long bone non-union were analysed. Information was obtained from the patient clinic visits, notes, radiographs and laboratory results. The cause(s) of the non-union were identified, recorded and divided into 4 groups; host, mechanical, dead bone/gap at NU site and infection. Results The mea...
Journal of Bone and Joint Surgery-british Volume, 2013
Proximal femoral fractures remain the most common reason for admission to hospital following orth... more Proximal femoral fractures remain the most common reason for admission to hospital following orthopaedic injury, with an annual cost of £1.7 billion to the National Health Service and social care services. Fragility fractures of the hip in the elderly are a substantial cause of mortality and morbidity. Revision surgery for any cause carries a higher morbidity, mortality, healthcare- and social economic burden. Which patients suffer failed surgery and the reasons for failure have not been established. The aim of this study was to determine which patients are at risk of failed proximal femoral fracture surgery, the mechanism and cause fo failed surgery and modifiable patient factors associated with failure of hip fracture surgery. From prospectively collected data of 795 consecutive proximal femoral fractures admitted between July 2007 and July 2008, all peri-operative and post-operative complications were identified. 55 (6.9%) patients were found to have developed a surgical complica...
Journal of Bone and Joint Surgery-british Volume, 2017
Nasal carriers of methicillin sensitive Staphylococcus aureus (MSSA) have an increased risk for h... more Nasal carriers of methicillin sensitive Staphylococcus aureus (MSSA) have an increased risk for health-care associated infections. There is currently no national screening policy for the detection ...
Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in... more Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop resistance ...
Aim The aim of this study was to determine whether the absence of periosteal reaction on plain ra... more Aim The aim of this study was to determine whether the absence of periosteal reaction on plain radiographs was predictive of exchange nail failure in lower limb diaphyseal fracture non-unions. Methods A consecutive cohort of 20 femora and 35 tibiae undergoing exchange nailing for diaphyseal aseptic (n=39) and septic (n=16) fracture non-union at a single centre from 2003 to 2010. Multiple causes of non-union were found in 29 patients (53%) with infection present in 16 cases (29.1%). Of this cohort 49 fracture non-unions had complete radiographic records (19 femora and 30 tibiae) allowing evaluation of the periosteal callus. The primary outcome was the number of number of revision procedures required to achieve union. Failure was defined was as the requirement of >two revision procedures to achieve union. Results The absence of periosteal callus from the fracture site on all four cortices conferred a relative risk ratio (RRR) 5.00 (p=0.006) of exchange nail failure in septic fractu...
Biomaterial infections associated with indwelling surgical devices are responsible for ~50% of al... more Biomaterial infections associated with indwelling surgical devices are responsible for ~50% of all nosocomial infections. The development of orthopedic biomaterial-associated infections comes at great physical and emotional cost to patients, resulting in substantial economic costs to healthcare providers. Understanding of its pathogenesis has progressed greatly since the biofilm hypothesis was first proposed. However, the biofilm hypothesis only partially elucidates the pathogenesis of these infections. A greater appreciation of the mechanisms underpinning immune evasion by common pathogens has highlighted a previous underestimation of the role this behavior has in the development of these troublesome infections. Recognition of the importance of the immune system interaction in the pathogenesis of biomaterial-associated infections will not only update our paradigm of this condition but also help to identify and develop potential therapeutic targets. This review aims to provide an overview of the pathogenesis of biomaterial-associated infections. It focuses primarily on the development of bacterial biofilms and the immune-evasive behavior of the most common orthopedic pathogens.
ObjectivesThe aim of this study was to review the current evidence and future application for the... more ObjectivesThe aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.MethodsA review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”.ResultsThe use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D ima...
External fixation is currently used as the definitive mode of fracture stabilisation in the manag... more External fixation is currently used as the definitive mode of fracture stabilisation in the management of ~50% of long-bone non-unions. Distinction between non-union and delayed union is a diagnostic dilemma especially in fractures healing by primary bone repair. This distinction is important, as non-unions are not necessarily part of the same spectrum as delayed unions. The aetiology of a fracture non-union is usually multifactorial and the factors can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. Infection is present iñ 40% of fracture non-unions, often after open fractures or impaired wound healing, but in 5% of all non-unions infection is present without any clinical or serological suspicion. General indications for external fixation include clinical scenarios where; 1) percutaneous correction of alignment, or mechanical stimulation of the non-union site is required; 2) fixation of juxta-articular or 'emmental' bone fragments is necessary; and 3) staged bone or soft tissue reconstruction is anticipated. Specific anatomical indications include infected non-unions of the tibia, humerus, and juxta-articular bone. External fixation is an essential tool in the management of fracture non-unions. However, with greater understanding of the outcomes associated with both external and internal fixation the relative indications are now being refined.
Objectives Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk fo... more Objectives Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. Methods Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. Results The prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = ...
Objectives Periprosthetic joint infection following joint arthroplasty surgery is one of the most... more Objectives Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time. Materials and Methods Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 mi...
To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management o... more To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management of periprosthetic joint infections (PJIs). Methods: Using the dissolvable bead biofilm assay, the minimum biofilm eradication concentration (MBEC) was determined for the most commonly used antimicrobial agents and combination regimens against staphylococcal PJIs. The established fractional inhibitory concentration (FIC) index was modified to create the fractional biofilm eradication concentration (FBEC) index to evaluate synergism or antagonism between antibiotics. Results: Only gentamicin (MBEC 64 mg/L) and daptomycin (MBEC 64 mg/L) were observed to be effective antistaphylococcal agents at clinically achievable concentrations. Supplementation of gentamicin with daptomycin, vancomycin or ciprofloxacin resulted in a similar or lower MBEC than gentamicin alone (FBEC index 0.25-2). Conversely, when rifampicin, clindamycin or linezolid was added to gentamicin, there was an increase in the MBEC of gentamicin relative to its use as a monotherapy (FBEC index 8-32). Conclusions: This study found that gentamicin and daptomycin were the only effective single-agent antibiotics against established Staphylococcus biofilms. Interestingly the addition of a bacteriostatic antibiotic was found to antagonize the ability of gentamicin to eradicate Staphylococcus biofilms.
The aims of the study were to review and analyse the reported series of debridement, antibiotics ... more The aims of the study were to review and analyse the reported series of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip arthroplasties (THAs) to establish the overall success and the influencing factors. Using a standardised recognised study protocol, meta-analysis of observational studies in epidemiology guidelines, a comprehensive review and analysis of the literature was performed. The primary outcome measure was the success of treatment. The search strategy and inclusion criteria which involved an assessment of quality yielded 39 articles for analysis, which included 1296 patients. The proportion of success following DAIR in the management of an infected THA appeared to improve after 2004 with a pooled mean proportion of success of 72.2%. For all reported series, from 1977 onwards, there was improved success with early debridement (< 7 days; 75.7%) and exchange of modular components (77.5%). There was a statistically non-significa...
This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. ... more This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. To my wonderful and long-suffering girlfriend Mary (whom I convinced to marry me by the end of my studies): thank you for supporting me throughout this endeavour.
Journal of Bone and Joint Surgery-british Volume, 2013
Introduction Fracture non-union is a devastating cause of patient morbidity. The cost of NU treat... more Introduction Fracture non-union is a devastating cause of patient morbidity. The cost of NU treatment ranges from £7,000 to £79,000. With an estimated 11,700 cases in the UK pa the financial implications are huge, potentially costing several hundreds of million of pounds annually. Successful outcome in the management of non-union is based upon correctly identifying the underlying cause(s) and addressing them appropriately. Aim The aim of this study was to assess the causative factors in non-union in order to optimize the management of non-union. The causes of NU were categorized into 4 groups (infection, dead bone/gap, host factors, mechanical). Method 100 consecutive patients who had surgery for long bone non-union were analysed. Information was obtained from the patient clinic visits, notes, radiographs and laboratory results. The cause(s) of the non-union were identified, recorded and divided into 4 groups; host, mechanical, dead bone/gap at NU site and infection. Results The mea...
Journal of Bone and Joint Surgery-british Volume, 2013
Proximal femoral fractures remain the most common reason for admission to hospital following orth... more Proximal femoral fractures remain the most common reason for admission to hospital following orthopaedic injury, with an annual cost of £1.7 billion to the National Health Service and social care services. Fragility fractures of the hip in the elderly are a substantial cause of mortality and morbidity. Revision surgery for any cause carries a higher morbidity, mortality, healthcare- and social economic burden. Which patients suffer failed surgery and the reasons for failure have not been established. The aim of this study was to determine which patients are at risk of failed proximal femoral fracture surgery, the mechanism and cause fo failed surgery and modifiable patient factors associated with failure of hip fracture surgery. From prospectively collected data of 795 consecutive proximal femoral fractures admitted between July 2007 and July 2008, all peri-operative and post-operative complications were identified. 55 (6.9%) patients were found to have developed a surgical complica...
Journal of Bone and Joint Surgery-british Volume, 2017
Nasal carriers of methicillin sensitive Staphylococcus aureus (MSSA) have an increased risk for h... more Nasal carriers of methicillin sensitive Staphylococcus aureus (MSSA) have an increased risk for health-care associated infections. There is currently no national screening policy for the detection ...
Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in... more Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop resistance ...
Aim The aim of this study was to determine whether the absence of periosteal reaction on plain ra... more Aim The aim of this study was to determine whether the absence of periosteal reaction on plain radiographs was predictive of exchange nail failure in lower limb diaphyseal fracture non-unions. Methods A consecutive cohort of 20 femora and 35 tibiae undergoing exchange nailing for diaphyseal aseptic (n=39) and septic (n=16) fracture non-union at a single centre from 2003 to 2010. Multiple causes of non-union were found in 29 patients (53%) with infection present in 16 cases (29.1%). Of this cohort 49 fracture non-unions had complete radiographic records (19 femora and 30 tibiae) allowing evaluation of the periosteal callus. The primary outcome was the number of number of revision procedures required to achieve union. Failure was defined was as the requirement of >two revision procedures to achieve union. Results The absence of periosteal callus from the fracture site on all four cortices conferred a relative risk ratio (RRR) 5.00 (p=0.006) of exchange nail failure in septic fractu...
Biomaterial infections associated with indwelling surgical devices are responsible for ~50% of al... more Biomaterial infections associated with indwelling surgical devices are responsible for ~50% of all nosocomial infections. The development of orthopedic biomaterial-associated infections comes at great physical and emotional cost to patients, resulting in substantial economic costs to healthcare providers. Understanding of its pathogenesis has progressed greatly since the biofilm hypothesis was first proposed. However, the biofilm hypothesis only partially elucidates the pathogenesis of these infections. A greater appreciation of the mechanisms underpinning immune evasion by common pathogens has highlighted a previous underestimation of the role this behavior has in the development of these troublesome infections. Recognition of the importance of the immune system interaction in the pathogenesis of biomaterial-associated infections will not only update our paradigm of this condition but also help to identify and develop potential therapeutic targets. This review aims to provide an overview of the pathogenesis of biomaterial-associated infections. It focuses primarily on the development of bacterial biofilms and the immune-evasive behavior of the most common orthopedic pathogens.
ObjectivesThe aim of this study was to review the current evidence and future application for the... more ObjectivesThe aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.MethodsA review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”.ResultsThe use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D ima...
External fixation is currently used as the definitive mode of fracture stabilisation in the manag... more External fixation is currently used as the definitive mode of fracture stabilisation in the management of ~50% of long-bone non-unions. Distinction between non-union and delayed union is a diagnostic dilemma especially in fractures healing by primary bone repair. This distinction is important, as non-unions are not necessarily part of the same spectrum as delayed unions. The aetiology of a fracture non-union is usually multifactorial and the factors can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. Infection is present iñ 40% of fracture non-unions, often after open fractures or impaired wound healing, but in 5% of all non-unions infection is present without any clinical or serological suspicion. General indications for external fixation include clinical scenarios where; 1) percutaneous correction of alignment, or mechanical stimulation of the non-union site is required; 2) fixation of juxta-articular or 'emmental' bone fragments is necessary; and 3) staged bone or soft tissue reconstruction is anticipated. Specific anatomical indications include infected non-unions of the tibia, humerus, and juxta-articular bone. External fixation is an essential tool in the management of fracture non-unions. However, with greater understanding of the outcomes associated with both external and internal fixation the relative indications are now being refined.
Objectives Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk fo... more Objectives Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. Methods Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. Results The prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = ...
Objectives Periprosthetic joint infection following joint arthroplasty surgery is one of the most... more Objectives Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time. Materials and Methods Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 mi...
To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management o... more To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management of periprosthetic joint infections (PJIs). Methods: Using the dissolvable bead biofilm assay, the minimum biofilm eradication concentration (MBEC) was determined for the most commonly used antimicrobial agents and combination regimens against staphylococcal PJIs. The established fractional inhibitory concentration (FIC) index was modified to create the fractional biofilm eradication concentration (FBEC) index to evaluate synergism or antagonism between antibiotics. Results: Only gentamicin (MBEC 64 mg/L) and daptomycin (MBEC 64 mg/L) were observed to be effective antistaphylococcal agents at clinically achievable concentrations. Supplementation of gentamicin with daptomycin, vancomycin or ciprofloxacin resulted in a similar or lower MBEC than gentamicin alone (FBEC index 0.25-2). Conversely, when rifampicin, clindamycin or linezolid was added to gentamicin, there was an increase in the MBEC of gentamicin relative to its use as a monotherapy (FBEC index 8-32). Conclusions: This study found that gentamicin and daptomycin were the only effective single-agent antibiotics against established Staphylococcus biofilms. Interestingly the addition of a bacteriostatic antibiotic was found to antagonize the ability of gentamicin to eradicate Staphylococcus biofilms.
The aims of the study were to review and analyse the reported series of debridement, antibiotics ... more The aims of the study were to review and analyse the reported series of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip arthroplasties (THAs) to establish the overall success and the influencing factors. Using a standardised recognised study protocol, meta-analysis of observational studies in epidemiology guidelines, a comprehensive review and analysis of the literature was performed. The primary outcome measure was the success of treatment. The search strategy and inclusion criteria which involved an assessment of quality yielded 39 articles for analysis, which included 1296 patients. The proportion of success following DAIR in the management of an infected THA appeared to improve after 2004 with a pooled mean proportion of success of 72.2%. For all reported series, from 1977 onwards, there was improved success with early debridement (< 7 days; 75.7%) and exchange of modular components (77.5%). There was a statistically non-significa...
Uploads
Papers by jerry tsang