Quantification of collagen organization in the peripheral human cornea at micron-scale resolution

The collagen microstructure of the peripheral cornea is important in stabilizing corneal curvature and refractive status. However, the manner in which the predominantly orthogonal collagen fibrils of the central cornea integrate with the circumferential limbal collagen is unknown. We used microfocus wide-angle x-ray scattering to quantify the relative proportion and orientation of collagen fibrils over the human corneolimbal interface at intervals of 50 μm. Orthogonal fibrils changed direction 1–1.5 mm before the limbus to integrate with the circumferential limbal fibrils. Outside the central 6 mm, additional preferentially aligned collagen was found to reinforce the cornea and limbus. The manner of integration and degree of reinforcement varied significantly depending on the direction along which the limbus was approached. We also employed small-angle x-ray scattering to measure the average collagen fibril diameter from central cornea to limbus at 0.5 mm intervals. Fibril diameter was constant across the central 6 mm. More peripherally, fibril diameter increased, indicative of a merging of corneal and scleral collagen. The point of increase varied with direction, consistent with a scheme in which the oblique corneal periphery is reinforced by chords of scleral collagen. The results have implications for the cornea's biomechanical response to ocular surgeries involving peripheral incision

Development of a mobile application-based system for recording pain and supporting pain management in patients with cancer

Pain is one of the most common symptoms experienced by patients with cancer at all stages of the disease. It is estimated that 32% of patients who experience pain do not receive effective treatment. Many cancer patients with increasing survival rates, most of them living in the community with inadequate support, continue to experience an accumulating symptoms burden and deterioration of function. Poor cancer pain management is a multifactorial issue attributed to numerous contributing factors including insufficient pain assessment and patient-related cognitive and communication barriers. The complex and dynamic nature of cancer pain adds unique challenges to pain classification and management, presenting a pressing need for high-quality descriptive research to define optimal management approaches. Collecting pain data, however, is challenging. The widespread use of mobile phones, along with people’s attachment to their phones, has made mobile health (mHealth) approaches an innovative and timely method for remotely delivering health interventions and collecting health data. Evidence shows that mHealth applications (apps) development is an emerging area of research. mHealth interventions have been increasingly explored in the context of various chronic health conditions, showing acceptability and encouraging results, but very little attention has been given to investigating these approaches in the field of pain management in cancer patients. As an attempt to fill this gap, this thesis presents the design, development, and early testing of a complex mHealth based intervention, the Pain Recording System, to support better pain management for UK-based adult cancer patients living in the community. The system sought to both support pain self-management and facilitate routine reporting of pain data to healthcare professionals (HCPs) and researchers. The thesis adopted the United Kingdom Medical Research Council (UK MRC) guidelines with the integration of the User-Centred Design (UCD) framework. The integrated approach enabled a systematic and iterative development and built the system to be underpinned by evidence and theory and informed by potential users, who are patients, HCPs, and researchers. Early testing showed that the developed system is feasible and acceptable and that potential users can see the benefits they may reap from it in relation to both practice of and research into pain management in patients with cancer. Importantly, the thesis concluded that there is a potential for mHealth interventions to be effective in optimising pain management for cancer patients. Further exploration, however, is necessary to provide conclusive evidence in relation to the system’s usability and acceptability, as well as to establish suitable approaches to implementation in the context of home-based palliative care

A microscopy study of the structural features of post-LASIK human corneas.

To study the structural features of human post-LASIK corneas.A pair of post-mortem donor corneas, from a 55-year old patient who underwent uncomplicated LASIK surgery five years previously, were bisected and fixed in 4% paraformaldehyde. The right cornea and one half of the left cornea were processed for light microscopy and scanning electron microscopy. One half of the right cornea was also examined by transmission electron microscopy.The flap-bed interface could be easily detected several years after LASIK and, although the flap appeared to be in close association with the stromal bed, there was a noticeable absence of reconnection between adjacent severed lamellae. Tissue gaps were evident at the flap margin, which once free of cellular components revealed the presence of a few bridging fibres.Examination of corneas five years after LASIK revealed evidence of primitive reparative scar development at the wound interface, but no reconnection of severed collagen lamellae. Such findings may explain the occurrence of flap dislocation following trauma in some patients months or years after surgery

Supporting Pain Self-Management in Patients With Cancer: App Development Based on a Theoretical and Evidence-Driven Approach

BackgroundTo inform the development of an intervention, it is essential to have a well-developed theoretical understanding of how an intervention causes change, as stated in the UK Medical Research Council guidelines for developing complex interventions. Theoretical foundations are often ignored in the development of mobile health apps intended to support pain self-management for patients with cancer. ObjectiveThis study aims to systematically set a theory- and evidence-driven design for a pain self-management app and specify the app’s active features. MethodsThe Behavior Change Wheel (BCW) framework, a step-by-step theoretical approach to the development of interventions, was adopted to achieve the aim of this study. This started by understanding and identifying sources of behavior that could be targeted to support better pain management. Ultimately, the application of the BCW framework guided the identification of the active contents of the app, which were characterized using the Behavior Change Technique Taxonomy version 1. ResultsThe theoretical analysis revealed that patients may have deficits in their capability, opportunity, and motivation that prevent them from performing pain self-management. The app needs to use education, persuasion, training, and enablement intervention functions because, based on the analysis, they were found the most likely to address the specified factors. Eighteen behavior change techniques were selected to describe precisely how the intervention functions can be presented to induce the desired change regarding the intervention context. In other words, they were selected to form the active contents of the app, potentially reducing barriers and serving to support patients in the self-management of pain while using the app. ConclusionsThis study fully reports the design and development of a pain self-management app underpinned by theory and evidence and intended for patients with cancer. It provides a model example of the BCW framework application for health app development. The work presented in this study is the first systematic theory- and evidence-driven design for a pain app for patients with cancer. This systematic approach can support clarity in evaluating the intervention’s underlying mechanisms and support future replication

Systematic review of intervention functions, theoretical constructs and cultural adaptations of school-based smoking prevention interventions in low-income and middle-income countries

Objective To identify the approaches and strategies used for ensuring cultural appropriateness, intervention functions and theoretical constructs of the effective and ineffective school-based smoking prevention interventions that were implemented in low-income and middle-income countries (LMICs). Data sources Included MEDLINE, EMBASE, Global Health, PsycINFO, Web of Science and grey literature which were searched through August 2022 with no date limitations. Eligibility criteria We included randomised controlled trials (RCTs) with ≥6 months follow-up assessing the effect of school-based interventions on keeping pupils never-smokers in LMICs; published in English or Arabic. Data extraction and synthesis Intervention data were coded according to the Theoretical Domains Framework, intervention functions of Behaviour Change Wheel and cultural appropriateness features. Using narrative synthesis we identified which cultural-adaptation features, theoretical constructs and intervention functions were associated with effectiveness. Findings were mapped against the capability-motivation and opportunity model to formulate the conclusion. Risk of bias was assessed using the Cochrane risk of bias tool. Results We identified 11 RCTs (n=7712 never-smokers aged 11–15); of which five arms were effective and eight (four of the effective) arms had a low risk of bias in all criteria. Methodological heterogeneity in defining, measuring, assessing and presenting outcomes prohibited quantitative data synthesis. We identified nine components that characterised interventions that were effective in preventing pupils from smoking uptake. These include deep cultural adaptation; raising awareness of various smoking consequences; improving refusal skills of smoking offers and using never-smokers as role models and peer educators. Conclusion Interventions that had used deep cultural adaptation which incorporated cultural, environmental, psychological and social factors, were more likely to be effective. Effective interventions considered improving pupils’ psychological capability to remain never-smokers and reducing their social and physical opportunities and reflective and automatic motivations to smoke. Future trials should use standardised measurements of smoking to allow meta-analysis in future reviews

Scanning electron microscopy images of a post-mortem LASIK cornea.

<p>The flap edge (yellow arrows in A) can be seen clearly. At higher magnifications, the flap edge appears separated from the adjacent corneal tissue (B). Towards the edge of the flap (at the flap/stromal bed interface), collagen lamellae appear to be in disarray and there is a notable absence of reconnection between adjacent severed lamellae (blue arrows in C). A vertical view of the flap edge shows a gap between the flap margin and the adjacent corneal tissue (white arrows in D). A few bridging fibres are seen to connect the flap to the stromal bed (green arrow in D). The black particles on epithelial and limbal surfaces appear to be adherent basal epithelial cells. Original magnifications for A, B, and C are ×40, ×400, ×1250 and ×3250 respectively.</p

Schematic cross-sectional (A) and overhead (B) view of the bisected right post-LASIK corneo-scleral button.

<p>Regions examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and light microscopy have been highlighted.</p