Diabetic foot ulcers (DFUs) impart a large burden on patients and the healthcare system in Canada. Health utility estimates are an integral part of determining the cost-effectiveness of treatments for DFUs. The objective of this thesis was to identify health utility estimates for patients with non-healing DFUs. A systematic review of studies reporting health utility estimates for non-healing DFUs was conducted and included nine studies. The quality of the studies, as it related to the health utility estimates for non-healing DFUs, was difficult to determine due to a lack of reporting of study and patient characteristics. The health utility estimates ranged from 0.44 to 0.89. None of the studies investigated for factors associated with the health utility of patients with non-healing DFUs. In addition, an exploratory regression analysis of data from a randomized controlled trial (RCT) of hyperbaric oxygen therapy (HBOT) in patients with chronic, non-healing DFUs was conducted. No factors were identified that were associated with health utility; however, the sample size was small and the analysis exploratory. Further research is required to identify such factors. Finally, a descriptive regression model, including several baseline factors, was created which provided a heath utility estimate of 0.647 for Canadian patients with non-healing DFUs; however, the results should be interpreted with caution, especially as some subgroups had very small numbers of patients (e.g., Wagner Grade of 4; patients with 4 or more wounds). In summary, guidance is lacking on the best methodology to conduct and analyze studies that provide estimates of the health utility of patients with non-healing DFUs, or any other health state, that are to be used to inform economic evaluations. Additionally, a tool is needed to aid analysts in critically appraising studies so that they can select the best estimate of health utility value to include in economic evaluations. / Thesis / Master of Health Sciences (MSc) / Diabetic foot ulcers (DFUs) impart a large burden on patients and the healthcare system in Canada. The objective of this thesis was to identify health utility estimates for patients with non-healing DFUs. A systematic review was conducted and included nine studies, for which health utility estimates ranged from 0.44 to 0.89. An exploratory regression analysis of data from an Ontario-based study in patients with non-healing DFUs was conducted. No factors associated with health utility were identified but further research is required. A descriptive regression model, adjusting for several baseline factors, provides a health utility of 0.647 for Canadian patients, but should be interpreted with caution. Guidance is needed on the best methodology to conduct studies to estimate the health utilities for use in economic evaluations and for a tool to critically appraise studies to help select the best estimate of health utility for inclusion in economic evaluations.

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Diabetic foot ulcers (DFUs) are a common and severe adverse event associated with diabetes, as 25% of diabetic patients will experience DFUs. The lack of effective DFU therapies results in 20% of diabetic patients requiring amputation. We first developed an algorithm to account for polydispersity when calculating nanoparticle concentration, which will reduce variability between batches and treatments. We also developed a novel 2-layer biomaterial, which combines anti-microbial properties of CLKRS peptide coated silver nanoparticles (CLKRS- AgNPs) with a pro-regenerative collagen matrix embedded with microscopic skin tissue columns (MSTC), to promote DFU wound healing. The collagen hydrogel formulation was optimized, and the physical properties, biocompatibility, and wound healing properties were assessed. Our results indicate that the CLKRS-AgNPs prevent bacterial growth and the collagen matrix provides a regenerative environment. Last, we developed and tested antimicrobial fabrics which can also be applied to chronic wounds, such as DFUs, to prevent and treat infections.

Background: The aim of this paper was to create an updated Australian guideline on footwear for people with diabetes. Methods: We reviewed new footwear publications, (international guidelines, and consensus expert opinion alongside the 2013 Australian footwear guideline to formulate updated recommendations. Result: We recommend health professionals managing people with diabetes should: (1) Advise people with diabetes to wear footwear that fits, protects and accommodates the shape of their feet. (2) Advise people with diabetes to always wear socks within their footwear, in order to reduce shear and friction. (3) Educate people with diabetes, their relatives and caregivers on the importance of wearing appropriate footwear to prevent foot ulceration. (4) Instruct people with diabetes at intermediate-or high-risk of foot ulceration to obtain footwear from an appropriately trained professional to ensure it fits, protects and accommodates the shape of their feet. (5) Motivate people with diabetes at intermediate-or high-risk of foot ulceration to wear their footwear at all times, both indoors and outdoors. (6) Motivate people with diabetes at intermediate-or high-risk of foot ulceration (or their relatives and caregivers) to check their footwear, each time before wearing, to ensure that there are no foreign objects in, or penetrating, the footwear; and check their feet, each time their footwear is removed, to ensure there are no signs of abnormal pressure, trauma or ulceration. (7) For people with a foot deformity or pre-ulcerative lesion, consider prescribing medical grade footwear, which may include custom-made in-shoe orthoses or insoles. (8) For people with a healed plantar foot ulcer, prescribe medical grade footwear with custom-made in-shoe orthoses or insoles with a demonstrated plantar pressure relieving effect at high-risk areas. (9) Review prescribed footwear every three months to ensure it still fits adequately, protects, and supports the foot. (10) For people with a plantar diabetic foot ulcer, footwear is not specifically recommended for treatment; prescribe appropriate offloading devices to heal these ulcers. Conclusions: This guideline contains 10 key recommendations to guide health professionals in selecting the most appropriate footwear to meet the specific foot risk needs of an individual with diabetes.

Neuropathy is one of the main long term complications of diabetes affecting 30-50% of patients. It is the major contributing factor for foot ulceration with a life time risk which may be as high as 25%. Hence neuropathy leads to reduced pain and pressure perception, anatomic deformities and an impaired microcirculation. More specifically, unperceived minor trauma results in cutaneous injury which when combined with an inadequate pressure induced vasodilator response leads to tissue breakdown and ulceration. Once ulcers form, healing may be delayed or difficult to achieve, particularly if infection occurs in the deeper tissues and bone which can then lead to amputation. In the UK, South Asians (people originating from India, Pakistan and Bangladesh) have an excess mortality for coronary artery disease (CAD), stroke and end-stage renal disease when compared to white Europeans. However, it has been shown that South Asian people with type 2 diabetes in the UK are only one third as likely to have a foot ulcer compared with White European diabetic patients. This has been attributed to lower levels of peripheral neuropathy in Asians, but has not been systematically explored in detail. In the present study, both neurological and vascular deficits in a group of South Asian and European patients with type II diabetes have been assessed. The results demonstrate that: • South Asian diabetic patients have poorer glycaemic control, but paradoxically lower triglycerides. This finding may be relevant to the finding that they have a lower incidence of neuropathy, as triglycerides have been related to neuropathy and foot ulceration. • South Asians compared to Europeans have better small fibre function and a trend for better structure (Intra epidermal nerve fibre density and corneal nerve morphology) and large fibre function assessed with nerve conduction studies. • South Asians have higher foot skin oxygenation and hyperaemic blood flow response to heating. • South Asians have a thicker epidermis and a trend for a better capillary density. Therefore these alterations may protect South Asians from the development of foot ulceration.

No / The establishment of a correct diagnosis links care to established guidelines and underpins all subsequent therapeutic activity. Problems can arise when definitions of disease overlap, as is the case with diabetic foot ulceration and pressure ulcers on the foot occurring in people with diabetes. In such cases, clinicians must ensure that patients receive a care bundle that recognises both the wound causation (pressure and shear) and the underlying pathology (diabetic neuropathy, potential foot architecture disruption and ischaemia). All patients with diabetes that have foot ulceration, irrespective of wound aetiology should, therefore, be seen by the multidisciplinary diabetic foot team. Care can then be optimised to include appropriate assessments, including assessment of peripheral perfusion, correct offloading, appropriate diabetic management, and general foot and skin care.

Diabetes är en sjukdom som i många fall kan leda till olika senkomplikationer, en av dem är fotsår. Att leva med diabetiska fotsår kan inverka på livskvaliteten, därför är det viktigt att få kunskap om vad som påverkar livskvaliteten för att kunna ge bättre omvårdnad och öka välbefinnandet. Syftet var att belysa vad som påverkar livskvaliteten hos personer med diabetiska fotsår. Datainsamlingen resulterade i 12 artiklar som besvarade studiens syfte. Granskning av artiklarna genomfördes och data kategoriserades. Fem kategorier framkom som visade att rädsla, smärta, immobilitet, kunskap och stöd påverkade livskvaliteten hos personer med diabetiska fotsår. Det fanns en rädsla för fördröjd sårläkning, utveckling av nya sår och att i framtiden eventuellt behöva amputera. Smärta från diabetiska fotsår upplevdes som frustrerande och var en av orsakerna till immobilitet vilket i sin tur skapade social isolering. Kunskap var betydelsefullt för att kunna förebygga uppkomsten av nya fotsår och för att de drabbade skulle kunna söka vård tidigare. För att kunna hantera vardagen var det därför viktigt att få stöd från olika personer i omgivningen. Sjuksköterskan kan förbättra omvårdnaden och skapa förutsättningar för bättre livskvalitet genom att se människan bakom fotsåret. / Diabetes is a disease which in many cases leads to various complications, one of them is foot ulcers. Living with diabetic foot ulcers can affect the quality of life, therefore it is important to gain knowledge about what affects the quality of life in order to provide better care and improve well-being. The aim was to highlight aspects that affects the quality of life in people with diabetic foot ulcers. The data collection resulted in 12 articles who responded to the purpose of the study. The examination of the articles was conducted and data was categorized. Five categories emerged which showed that fear, pain, immobility, knowledge and support affected the quality of life among people with diabetic foot ulcers. There was a fear of delayed wound healing, development of new wounds, and for the risk of amputation in the future. Pain from diabetic foot ulcers was perceived as frustrating and was one of the causes of immobility, which in turn created the social isolation. This knowledge was important in order to prevent the occurrence of new foot ulcers so that those affected could seek treatment earlier. In order to manage everyday life, it was therefore important to receive support from different people in the surrounding. The nurse can improve the care and create better quality of life by seeing the person behind the foot ulcer.

Diabetes is a growing public health problem that can lead to serious complications for the pa-tient such as foot ulcers and amputations. For affected patients the foot ulcers causes suffer-ing, pain and impaired health. The foot ulcers also contribute to major costs to the society and affects healthcare resources hard. A large part of the district nurse's work consists of wound care. Therefore it is important that the district nurse possess adequate knowledge of wound dressings to promote wound healing and thereby shorten the wound healing time. The aim of the study was to examine the wound healing time due to treatment with antiseptic or non-antiseptic dressings in elderly patients with diabetes and foot ulcers. The method used was a quantitative register study with a retrospective and descriptive design. Patients included in the study were 241 men and women aged ≥ 65 years with diabetes and healed foot ulcers. Men were represented by 68 % (n=164) and women by 32 % (n=77). The results showed no signif-icant difference in wound healing time due to treatment with antiseptic or non-antiseptic dressings. The most common non-antiseptic dressing used was polyurethane foam and the most common antiseptic dressing used was silver dressing. More research to compare wound healing time between non-antiseptic and antiseptic dressings in elderly patients with diabetes and foot ulcers are needed. District nurses need to increase their knowledge within different dressings and its positive and negative effects.

Delivery vehicles are necessary for many therapeutics to overcome the various challenges in their path. It is clear, however, that the relationship between delivery vehicles and the immune system is a complex one. One such delivery vehicle is the lipidoid nanoparticle, which has been shown to be potent in several cell types. This thesis details the first time lipidoids have been used for wound delivery, and demonstrates the successful silencing of an inflammatory protein, TNFα, in the context of diabetic ulcers. Knockdown is seen in an in vitro macrophage-fibroblast coculture model, as well as in nondiabetic and diabetic mice wound models. Lipidoids silence roughly half of the TNFα gene expression in the diabetic wound and have been shown to help the wound close faster than untreated controls. Of course, immune activation can decrease therapeutic efficacy or trigger dangerous reactions in the patient. Learning more about what chemical moieties cause an immune response would allow for the design of a particle that could better resist immune clearance and avoid the creation of a secondary response. This thesis investigated the effect of a lipidoid library on the immune system using a two pronged approach. The lipidoids were first tested against human peripheral blood mononuclear cells and then were injected into mice to probe the in situ immune response. Several types of B cells were examined in this latter case, namely germinal center B cells, plasma cells, and memory B cells. A T cell dependent response occurred, favoring memory B cells for most of the lipidoids tested. There was an increase in free antibody in the blood that reflected this increase in antibody producing cells. Nitrogen rings and carbon tail lengths of eleven and twelve carbons were particularly reactive, though it appears that the amine head group determines immune response more than the tail. Further work will analyze whether these increases in immune cells reflect a loss of therapeutic efficacy, as current ramifications are unclear. An in-depth T cell subset analysis with flow cytometry would also help complete the picture.

Introduktion: Fotsår är en vanlig komplikation hos patienter med diabetes mellitus. Diabetiska fotsår leder till stort lidande, där patientens liv påverkas. Det finns en ökad risk för amputation som framtida utfall. Det krävs ett multidisciplinärt team inom sjukvården för att behandla dessa sår.   Syfte: Att beskriva hur personer med diabetes upplever att leva med diabetiska fotsår.  Metod: Litteraturstudie baserat på 12 kvalitativa originalartiklar. Sökning utfördes i databaserna PubMed och CINAHL. Kvalitetsgranskning har gjorts utifrån SBS´s mall för bedömning av studier med kvalitativ metod (SBU, 2020) och en manifest innehållsanalys har använts för resultatanalysen.  Resultat: Analysen resulterade i sju kategorier: Psykisk påverkan, lidande, funktion, sjukvård, arbete & ekonomi, framtid samt familj & vänner. Patienterna beskrev främst negativa upplevelser av att leva med fotsår där fysiska, sociala, socioekonomisk och psykologiska konsekvenser identifierades. Upplevelser som nedstämdhet, känslan av att vara en börda, minskad självständighet och rädsla för amputation uttrycktes. Slutsats: Fotsår bidrog till att patienterna upplevde både negativa och positiva upplevelser, känslor och erfarenheter. För att ge den bästa möjliga omvårdnad behöver sjuksköterskan se patienten i ett helhetsperspektiv för att kunna tillgodose alla aspekter av patienternas liv som påverkas fotsåret. / Introduction: Foot ulcers are a common complication in patients with diabetes mellitus. Diabetic foot ulcers cause great suffering where different aspects of a patient's life are affected, there is an increased risk of amputation present. In order to treat the ulcers health care need to implement a multidisciplinary team approach.  Aim: To describe how diabetic patients experience living with diabetic foot ulcers.  Method: Literature study based on 12 qualitative original articles. Literature searches were performed in the databases PubMed and CINAHL. A quality review was performed and based on SBU’s template for assessment of studies with qualitative methodology (SBU, 2020) and manifest content analysis was used for the result analysis.  Results: Analysis resulted in seven categories: Psychological impact, suffering, function, health care, employment & economy, future and family & friends. Patients mainly experienced negative implications to living with diabetic foot ulcers, where physical, social, socioeconomic and psychological consequences were identified. Experiences such as depression, the feeling of being a burden, reduced independence and fear of amputation were expressed.  Conclusion: Diabetic foot ulcers contributed to patients experiencing both negative and positive experiences and feelings. To provide good care nurses need to apply a holistic perspective and approach to their practice, in order to cater to all aspects of patients' life that are affected by the diabetic foot ulcers.