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Pressure ulcers (PUs) and incontinence-associated dermatitis (IAD) are types of skin damage that result from prolonged exposure to external insults including pressure, shear, friction, and moisture. The clinical symptoms, which often lead to chronic wounds, can involve erythema, skin swelling, oedema and skin breakdown. It is imperative to detect early signs of these conditions prior to chronic damage. However, subjective visual and tactile skin assessments typically used by clinicians lack predictive capability. Objective biophysical approaches have been suggested to provide the means of monitoring the early signs of damage, although further evidence is required to establish their performance in a range of clinically relevant situations. The goal of the doctoral research is to utilise an array of non-invasive biophysical sensors to understand the pathophysiological changes in the skin following different insults associated with PUs and IAD. This thesis presents the results from a series of complimentary retrospective and prospective studies. These involved the analysis of established data from the host lab, a survey of skin damage resulting from the application of personal protective equipment (PPE), and two prospective lab-based studies. The former involved the recruitment of able-bodied volunteers and healthcare workers who were exposed to moisture and mechanical loads through incontinence pads and lying postures, and respirator protective equipment (RPE), respectively. These findings were used to inform a cohort study of hospitalised patients with stage I pressure ulcers. Results revealed that prolonged exposure of the skin to mechanical loads and moisture can disrupt its barrier function, as evidenced by enhanced values of trans-epidermal water loss and stratum corneum hydration. Furthermore, among the biophysical skin parameters evaluated, TEWL and hydration were able to distinguish between compromised and healthy adjacent skin sites, but not between different insults. During a COVID-19 study of adverse reactions to PPE, cohorts of healthcare workers revealed that they had indentation marks, pressure damage, itchiness, rashes, and spots. The subsequent study of biophysical changes in skin health identified distinct changes in skin barrier function and hydration over vulnerable bony landmarks on the face (bridge of the nose) associated with RPE application. Findings from this study showed that the outputs of these parameters were influenced by the subject extrinsic and intrinsic factors, namely body mass index and daily working hours. The final clinical study revealed highly localised changes (< 5mm) in skin barrier function over the pressure ulcer site. In contrast to the lab-based studies, skin hydration did not differentiate between healthy and damaged skin. Complementary analyses also revealed the important role of inflammatory cytokines in the early detection of skin compromise, as well as the potential of epidermal corneocytes as novel biomarkers reflective of changes in skin health. The use of biophysical tools to monitor local changes in skin health could represent an important adjunct to clinical practice, which currently relies on subjective skin assessment. However, to support its wider translation in different care settings, future research is required to analyse time-dependent changes in these parameters, in both acute and long-term care facilities, to assess the prognostic value when determining skin status (healing or progressing to wounds). In addition, engagement with healthcare workers to analyse the barriers and facilitators to adoption along with the cost-effectiveness of introducing these tools is needed prior to wider adoption in practice.

There are many clinical situations in which skin and soft tissues are subjected to sustained mechanical loading, particularly in individuals with restricted mobility. This can result in the breakdown of soft tissues in vulnerable areas, leading to the development of pressure ulcers (PUs). For several decades, interface pressure measuring systems have been employed to assess the magnitudes of pressures at the support surface interface of individuals at risk of developing PUs, typically to evaluate the short-term performance of pressure relieving systems (e.g. mattresses) and promote optimal postures. These technologies have recently been adapted to monitor over extended periods, providing the opportunity to estimate clinically-relevant temporal trends in posture and mobility. However, their ability to detect individual postural movements has not been established. Therefore, the present research was designed to assess the combination of pressure monitoring and intelligent data processing for the detection of postural changes during prolonged lying. A series of experimental studies utilised biomechanical parameters derived from pressure distribution and signals representative of body segmental movements using actimetry systems. Continuous measures were taken in cohorts of healthy individuals during evoked lying postures involving a raised head of the bed (HOB) and automated lateral tilt. The sensitivity and specificity of parameters for detecting changes in defined lying postures were examined. Data optimisation with Receiver Operating Characteristics (ROC) and Principal Component Analyses were performed to establish the most robust parameters, thus reducing the large volume of data associated with long-term monitoring. In particular, contact area and centre of pressure signals at specific body regions i.e. whole body and buttock, proved the most accurate of the interface pressure parameters, with ROC curve values (AUC) exceeding 0.5 for the majority of evoked postures. Signals derived from actimetry at the sternum also proved accurate in detecting postural movements, with the majority of postures revealing high AUC values. These parameters were combined with an automated detection method and machine learning algorithms to develop a robust methodology capable of predicting the frequency and magnitude of postural changes. The methodology was refined to accommodate a random sequence of postures on different support surfaces. The final automated methodology was then tested on pressure monitoring data from a small cohort of spinal cord injured subjects, who are vulnerable to PU development. Prediction of lying postural changes was achieved with a derivative threshold - based method, which yielded an accuracy of 100% when pressure signals were combined with body angles, and >85% for pressure signals in isolation. Prediction of lying postures was achieved by applying machine learning classifiers to either a combination of actimetry and pressure data or the pressure parameters in isolation. The most accurate combination of clinically relevant parameters involved pressure signals and body angles, achieving an average accuracy of ≥88%.The series of experiments and analytical approaches undertaken in this project contributed to the development of a semi-automated methodology based on robust biomechanical parameters for prediction of posture and mobility during prolonged lying. This was translated to a clinical data set, where long-term pressure monitoring was employed to evaluate previously unknown postures and provide the objective means to evaluate whether repositioning for pressure ulcer prevention adhered to international guidelines. Although further improvements are required for the analysis and visualisation of pressure data in clinical settings, this novel methodology has the potential to provide objective indication of posture and mobility which will inform effective personalised PU prevention.

It is well established that hospitalised neonates are at risk of iatrogenic skin damage. However, published prevalence and incidence rates vary, with the proportion of different types of damage unknown. It is unclear which factors act as barriers to and facilitators of skin care in this population. This motivated the aims of the thesis, which was to identify potential determinants of change related to the prevention of skin damage in neonatal units. In order to achieve this aim a multiphase mixed methods approach was adopted. This included an analysis of nursing staff practice and beliefs using a 19-part survey, a focus group with neonatal nurses, and interviews with lead Tissue Viability Nurses (TVNs). In addition, a prevalence and incidence study of all forms of skin damage on two neonatal intensive care units was conducted. The free text comments from the survey, the focus group, and the interviews were analysed using a thematic analysis approach informed by the determinants of change outlined in the Implementation of Change Model. This revealed concerns about damage from medical devices and diaper dermatitis. Participants reported that peer-to-peer learning represented their main source of skin education, and that balancing skin care with other clinical needs was challenging. It was also apparent that the unique nature of the neonatal unit acts as a barrier to reporting damage, involving outside specialists, and accurately classifying wounds. Prevalence data were collected from 54 neonates, 21 of whom presented with some form of skin damage (38.9%). Incidence data were collected from 51 neonates, 36 of whom developed some form of skin damage (70.6%). Of these, 23 neonates developed diaper dermatitis (45.1%), 23 developed damage associated with a medical device (45.1%), and four developed immobilityrelated pressure ulcers (7.8%). No single device was identified as the primary cause of devicerelated damage, with 12 of the 21 devices observed during the study noted to be associated with damage. Logistic regression analysis found that lower gestational age at birth was associated with an increased risk of developing both general skin damage and device-related damage. It was not, however, associated with an increased risk of developing diaper dermatitis. In summary, this thesis has improved our understanding of the issues and complications currently facing hospitalised neonates in relation to skin care. There are a number of clinical implications for these findings. Proposed practice changes include the introduction of skin rounds and 'skin champions', standardised guidelines for when damage should be escalated to TVNs, and training for neonatal nurses on wound assessment and classification. Proposed areas for future research include the development of medical devices that take into consideration the unique requirements of preterm skin. Further qualitative research is needed with healthcare professionals and parents focussing on the role and experiences of the wider care team. In conjunction with the findings of this thesis, these next steps will allow nurses and other professionals to better protect and promote skin health in these most vulnerable of patients.

Pressure ulcers (PUs) are a burden to individuals’ physical, mental and social wellbeing (Spilsbury et al. 2007), with a financial impact for individuals, healthcare organisations and society (Gorecki et al. 2009; Demarré et al. 2015b). A team-based approach towards their prevention has long been promoted as best practice, yet little is known about its application or efficacy in practice (Gottrup et al. 2001; Cramp et al. 2004; Bergquist-Beringer and Makosky Daley 2011; NICE 2014). The aim of the thesis was to explore the knowledge, attitudes and perceptions of healthcare staff in order to understand barriers and facilitators to interdisciplinary PU prevention. A sequential mixed methods design was adopted to achieve this aim, with questionnaires, focus groups and interviews conducted with health care staff from a community NHS Trust. The results of these questionnaires were used to inform focus groups and interview discussions with nurses/healthcare assistants (HCAs), allied health professionals (AHPs), non-caseholding clinicians and tissue viability nurses (TVNs). These data were coded and matched to determinants of behavioural change using two taxonomies, which subsequently established a series of techniques for use within an interdisciplinary intervention (Abraham and Michie 2008; de Bruin et al. 2009; EPOC 2015). The integrated quantitative and qualitative results established the following determinants of behaviour change: knowledge, attitude, awareness, social influence, organisational factors and structural factors. Participants demonstrated a high level of knowledge in relation to ‘aetiology and development’, but poor knowledge of ‘preventive measures’, with nurses and AHPs displaying the same levels of knowledge overall. However, nurses were found to have a more positive attitude and a greater personal competency to PU prevention that the pooled data for AHPs. Nevertheless, when divided by profession occupational therapists and HCAs reported a more positive attitude than nurses. While participants demonstrated strong awareness of the impact of PUs, there was a limited understanding of the role that different professional groups could play in prevention. Furthermore, there was some variability in the responses from a variety of professions over whether PUs were preventable in high risk groups. Consequently, it was reported that in some areas the focus of practice had changed from prevention to ensuring that if a PU did occur it would be classified as unavoidable. Organisational and structural barriers to achieving prevention included insufficient time and staffing; while for team-based practice, participants described the impact on communication of nursing and AHP teams working from different locations. The importance of effective leadership and education were identified as facilitators to achieving an interdisciplinary approach to PU prevention. An interdisciplinary training programme was developed and feasibility tested with one community team based on the previous results and a framework of the characteristics of a good interdisciplinary team (Nancarrow et al. 2013). The content and format of the programme was considered acceptable, however the tools used to measure the programme’s effectiveness lacked sensitivity to detect a meaningful difference. The programme focused on the individual and team-based determinants of practice, however, achieving an interdisciplinary approach to PU prevention requires the integration of other practice determinants. These include process, organisational and contextual factors (Reeves et al. 2010).

Incontinence-associated dermatitis (IAD) is an inflammatory response caused by the prolonged contact of the skin to urine and/or faeces. Although several theories exist to explain the pathophysiology of IAD, most are based on animal models, or derived from studies on the related condition of diaper dermatitis ('nappy rash') that occurs in babies. Thus, their relevance to IAD in adults is limited and the underlying mechanisms of IAD remain poorly understood. The motivation for this novel work was to develop and validate both in vivo and in vitro techniques to simulate IAD to provide empirical evidence on the biophysical and biochemical disruption of skin in IAD. The integrity of the skin was evaluated by measuring changes in skin blood flow, transepidermal water loss (TEWL), hydration of the stratum corneum (SC) and skin surface pH. Synthetic-urine (s-urine) and a proteolytic solution were used to simulate the effects of urinary- and faecal- incontinence, respectively. The release of inflammatory biomarkers was investigated in vivo by two distinct sampling techniques, namely microdialysis and Sebutape™. In vitro investigations were also conducted with human keratinocytes to support in vivo studies, with cell viability and the secretion of inflammatory cytokines serving as output measures. Results of the current study showed that while urine disrupts the integrity of intact skin, causing a significant increase in skin blood flow, TEWL, SC hydration and skin surface pH (p < 0.05), its effects are not pH dependent. In contrast, exposure of the skin to the proteolytic solution led to an enhanced increase in these biophysical parameters. This was also supported by in vitro keratinocyte experiments which indicated that the proteolytic solution is more deleterious than urine, as revealed by a decreased cell viability. Of particular importance is the finding that the permeability and susceptibility of the skin to urine depends on skin condition, with chemically-irritated skin, exacerbated by frequent cleansing activities, presenting an increased risk of IAD. Increased skin permeability was also associated with an elevated skin surface pH. In this respect, in vitro investigations highlighted that pH is an important regulator for the function of keratinocytes and consequently the maintenance of skin barrier function. Additionally, it was shown that the effects of urinary pH are time-dependent. Importantly, exposure of skin to urine and the proteolytic solution resulted in an increase in the release of pro-inflammatory biomarkers and indeed during exposure there was a time-dependent accumulation of biomarkers in the interstitium. In particular, a significant increase was estimated in the ratio of IL-1α/IL-1RA (p < 0.05) following exposure to s-urine. Additionally, results demonstrated that s-urine resulted in an increase in IL-1α, whereas the proteolytic solution caused a marked increase in TNF-α. The increase in pro-inflammatory cytokines following exposure to urine was further supported by the in vitro studies. In these studies, an increase in the pH upregulated the release of inflammatory biomarkers, more particularly IL-1α. These data propose that in future studies, IL-1α and TNF-α have the potential to serve as responsive markers of skin damage caused by incontinence. The findings presented in this thesis extend current knowledge on IAD, with noteworthy implications for the direction of future IAD research and the development of targeted clinical interventions. Additionally, the data add to the scientific body of evidence and propose that the damage caused by frequent cleansing activities and the release of inflammatory biomarkers are two mechanisms implicated in the pathophysiology of IAD. Additionally, an internal pH mechanism for keratinocytes function is also proposed, which needs to be further examined. Overall, this work establishes the methods to investigate IAD in an experimental setting, which can be translated to clinical studies.

Despite lymphatic function regularly being proposed as one of the causative mechanisms in the development of pressure ulcers, there has been a paucity of research regarding the effect of compression on lymphatic function in human tissues. This has motivated the present work, which has developed and validated techniques to safely assess lymphatic function and concomitantly measure the physiochemical response in the skin, directly under and following the application of a uniaxial load in human volunteers. Lymphatic function was assessed through optical imaging of an intradermally injected near-infrared fluorophore, namely indocyanine green (ICG), which is rapidly cleared in lymph. Pro-inflammatory biomarkers were recovered by two minimally invasive collection techniques involving microdialysis and SebutapeTM. Through the application of established image processing concepts to NIR lymphangiography for the first time, a method for objectively quantifying parameters of active lymphatic clearance is also described. The results of the study suggest that applied pressure of 60 mmHg for a period of 40 minutes can lead to changes in both novel pro-inflammatory and lymphatic parameters, not previously described in the literature. During the loading period, induced expression or accumulation of IL-6 and IL-8 in the interstitium was observed (p < 0.01). For IL-6, this upregulation was sustained for over 40 minutes post loading (p < 0.01). The same loading protocol was associated, through categorical analysis, with impaired lymph formation in lymphatic capillaries and disrupted valve function in collecting vessels directly under the load. The velocity of active lymphatic drainage along the loaded pathway was also significantly reduced (p < 0.05).The findings from this thesis support the proposal that impaired lymphatic function, with a corresponding accumulation of harmful biomolecules, are feasible mechanisms which can contribute to the development of pressure ulcers. The present study strongly supports further exploration of these hypotheses using the techniques described.

Pressure ulcers represent a debilitating condition for patients and present a significant challenge for healthcare professionals. To determine the risk of pressure ulcer development, patients are typically assessed with pressure ulcer risk assessment scales. Bed-bound patients deemed at risk of pressure ulcers may receive a range of interventions, including regular repositioning by nursing staff. However, this is resource intensive and could be augmented by mechanical lateral rotation systems, although there is a paucity of research examining these systems. Several experimental studies were conducted, utilising physical output parameters and comfort assessments to examine the efficacy and acceptability of two lateral rotation systems, when compared to traditional repositioning, in cohorts of healthy participants. In addition, a study sought to determine the inter-practitioner variability of traditional repositioning. An integrative review of pressure ulcer risk assessments scales was further undertaken, to update and extend previous reviews. A number of differences were observed in the physical and comfort data, some of which were device dependent. A trend towards fewer instances of compromised tissue viability was observed during traditional repositioning, although some participants preferred turning by means of a lateral rotation system. Considerable variation was noted in the repositioning technique employed by practitioners, even after written guidance, and offloading of vulnerable areas was not always achieved. Ninety-four risk assessment scales were identified, but only 15% of these scales were assessed for inter-rater reliability. The methodological quality of such studies was often poor. Lateral rotation systems may provide an adjunct to repositioning by traditional methods, but the design is important, both in terms of efficacy and acceptability. Practitioners should be provided with practical training, focusing on the procedural aspects of repositioning. Further high-quality primary research is required to evaluate existing risk assessment scales.