Computational studies on light‐tissue interactions in medical treatment and diagnosis have offered deeper insights in the processes underlying laser treatments and fluorescence measurements. I apply this approach in the study of fluorescence detection and of laser therapy. First, I investigate three methods of fluorescence detection and the reported contrast between healthy skin and malignant tissue. I varied the concentration of haemoglobin in the target, the concentration of melanin in the epidermis, the scattering of light in the skin, the depth at which the target is located in the skin, the width of the target, the thickness of the target, the concentration of photosensitizer in the target, and the concentration of photosensitizer in the skin. My findings confirm previous clinical studies in that the auto‐fluorescence corrected fluorescence detection method generally shows a higher contrast than the other methods. The results support earlier clinical studies and are in accordance with expert experience. Second, I study laser therapy for psoriasis. In a series of simulations, I analyse three types of pulsed dye laser systems and one IPL system. The investigated biological effects are heat shock proteins, hyperthermic tissue damage and vasoconstriction of the microvasculature. The changes in the skin concern blood volume, blood oxygenation and scattering in the epidermis. The calculations show that there are some notable differences in the effect changes in the composition of psoriatic tissue has on the efficacy of laser and IPL therapy. Still, Inter‐device variance was more prominent than intra‐geometry variance. My study adds to the understanding of fluorescence detection of keratinocyte skin cancers, as well as that of laser therapy for psoriasis. Additionally, it offers potential avenues for increasing the efficacy and efficiency of these therapies.

In order to understand the role of the formulation components in topical drug delivery it is necessary to separate the various contributing factors, these include thermodynamic activity effects, changes in the ionisation state of the permeant and alteration of the membrane properties. Three model permeants, ibuprofen, salicylic acid and acetaminophen were selected to represent a range of physicochemical properties. Solubility and distribution behaviour of ibuprofen and salicylic acid was determined and demonstrated how the addition of cosolvent could impact upon the permeation of the two weak acids by altering the ionisation state of the permeants. The cosolvents, (typical formulation excipients) were water, propylene glycol ethanol, mineral oil, miglyol and Transcutol . To begin with binary combinations were tested, moving on to ternary combinations more representative of an actual formulation. Silicone membranes were used to investigate the diffusional properties of the model permeants. Similarities in the behaviour of the permeants in the selected solvents were observed. Ibuprofen was found to have a higher permeation rate than salicylic acid possibly because of the hydrophobic nature of the Silicone membrane. Analysis of diffusion profiles using a nonlinear curve fitting procedure revealed that the selected vehicles enhanced the permeation of ibuprofen and salicylic acid by increasing partitioning into the membrane. Acetaminophen was found to oxidise in the presence of hydrogen bonding solvents, and for this reason was eliminated from the study. Diffusion experiments were conducted using an established ATR-FTIR approach but the data interpreted using sophisticated chemometric approaches which allowed the deconvolution of the IR signals of all permeating species and the membrane. Using this approach it was possible to examine the individual profiles from multi-component formulations. Using data from traditional diffusion experiments alongside information obtained from ATR-FTIR diffusion experiments using a new method of analysis allowed a deeper insight into the role of the solvent in the permeation process. Data from ATR-FTIR experiments revealed that ethanol permeated silicone membrane at a faster rate than the other solvents studied. This finding was in line with evidence from Franz-type diffusion experiments in which flux was consistently higher from formulations containing ethanol. Where possible, the effect of the same vehicles on the permeability properties of human skin was examined. The vehicles selected were predominantly influencing the partition of the drug into the skin rather than the diffusion coefficient.

To conduct a pilot survey to assess acceptance of mobile teledermoscopy (MTD) by primary care nurse practitioners (NPs) working in Arizona.

The geriatric population (65 years or older) represents a large portion of dermatology patients and is growing rapidly. This population is hypothesized to face several exacerbated barriers to dermatological healthcare, often resulting in the deferral of necessary dermatological healthcare. This avoidance behavior unnecessarily increases morbidity and mortality of this population due to dermatological diseases. The behaviors of this group towards their dermatological healthcare must be assessed for public policy to help fix the disparity seen in their dermatologic care. A cross-sectional online survey was carried out among a randomly selected sample of 609 registered SurveyMonkey® users aged 65 years or older across the continental United States. Multiple linear regression analysis of the data revealed a negative relationship between perceived barriers to care and self-reported usability of telemedicine (p=0.01). This analysis also revealed several gender differences; females were more likely to be concerned with “cosmetic/aging” (p<0.0001) and males reported both higher prevalence of skin cancer (p<0.005) and higher concern for developing skin cancer (p=0.05).

No description available.

A 22-year-old male college student presented to primary care with a pruritic rash on his mid abdomen for the past 2 weeks. He reported mild to moderate pruritus and had been scratching the area above his belt buckle.

Epidermolysis Bullosa (EB) is a rare genetic disorder that causes extreme skin fragility and blistering in patients, significantly impacting their quality of life. EB can be classified into various subtypes, each with a unique genetic profile and diverse physical symptoms. Due to the heterogeneous inheritance patterns of EB, a cure remains yet to be found. However, various symptomatic treatments have been developed and continue to be developed to relieve pain and itching for patients and improve their quality of life. These treatments can be divided into topical treatments, some of which have undergone clinical trials, and systemic treatments, which target the upregulation of inflammatory pathways. Potential curative treatments in development for EB include gene replacement therapy, gene editing therapy, RNA-based therapy, revertant mosaicism, cell-based therapy, protein therapy, and protein codon read-through. Recent advancements in gene therapy and stem cell therapy show promise for a cure for EB in the future. Stem cell therapies utilizing umbilical cord blood-derived mesenchymal stem cells or dermal mesenchymal stromal cells, among others, have shown potential in clinical trials, but further research is required before they can be implemented in a clinical setting. On the other hand, B-VEC, a topical gene therapy, and EB-101, an autologous ex-vivo gene therapy, have undergone more extensive research and are awaiting FDA approval. The ongoing research and development of these therapeutic modalities provide hope that a cure will soon be found for this devastating disease.

Consideration of broader outcomes of disease, especially those exclusively experienced and reported by the patient, such as HRQOL, is not only consistent with the ‘whole person’ view of health contained in the 1948 WHO definition, but is also a prerequisite to building health-care systems that are responsive to the needs of the patients. For chronic skin diseases, such as hyperhidrosis, these provide a useful indicator of how a patient feels and functions disease for both practical and methodological reasons. The aims of this study therefore were to investigate the impact of hyperhidrosis on patients’ HRQoL using a mix of qualitative and quantitative methods. In addition, a further aim was to develop and validate a disease-specific instrument for assessing HRQoL in hyperhidrosis. In pursuing the above aims, the feasibility of applying online social networking sites for outcomes research in dermatology was assessed. Patients were recruited through online social networking communities related to hyperhidrosis for all stages of the study. Interviews, focus groups and surveys were used for collecting qualitative data from patients (n = 71) to understand quality of life issues of patients, and to provide the content of the new instrument. Dermatologists (n= 5) and patients (n=7) took part in the content validation of the HidroQoL©. Item reduction and the development of the scale’s structure was carried out through several field-testing studies (n: USA, 559; UK, 115), using the item response theory (IRT) Rasch model and factor analyses. Further psychometric testing was performed in a separate study (n = 241). Distribution-based methods were applied in establishing minimum clinically important difference (MCID). A thematic analysis of the qualitative data collected produced 29 quality of life themes and 102 sub-themes, forming the content for the initial 49-item HidroQoL©. The two expert panels judged the instrument as content valid, with a few suggestions. The Rasch analysis modelling led to the collapsing of response categories (from five to three) and the reduction in number of items (from 49 to 18), to ensure a perfect model fit. Factor analyses supported both a single- and a two-factor structure. In subsequent construct validation study the HidroQoL correlated with the DLQI (rs = 0.572, p < 0.01) and the Skindex-17 (rs = 0.551, p < 0.01). Reliability was high (Cronbach alpha = 0.9; test-retest ICC = 0.93). The scores were sensitive to change in patients’ disease severity (standard response mean = 0.8, 95% C.I: 0.34-1.27). The scale banding proposed for the HidroQoL score is as follows: 0 – 1, no effect at all; 2 – 11, small effect; 12 – 22, moderate effect; 23 – 32, large effect; 33 – 36, very large effect. The MCID values were 1.94 – 3.07, for generalised v hyperhidrosis, 2.16 – 4.36, for axillary hyperhidrosis, 2.15 – 3.39, for palmo-plantar hyperhidrosis. An MCID of three is currently being proposed for all types of hyperhidrosis. This study has provided the initial evidence supporting the appropriateness of the content of the HidroQoL and validity of inferences from its scores for assessing HRQoL in hyperhidrosis. In addition, the availability of MCID estimates for the HidroQoL will facilitate its clinical interpretation in both research and routine clinical practice. This study has also demonstrated how CTT and IRT can be integrated in the development and validation of a new generation of HRQoL instruments, using social network for patient recruitment.

No description available.

Examining 20 human wound bed biopsies (pilonidal sinus and venous leg ulcers), significant differences were observed between the subpopulations of wound macrophages in acute healing and chronic non-healing wounds. The results exhibit that within the acute wound there is an accumulation of early stage macrophages (mean 20.8, SD 8.6) differentiating from monocytes which become activated and contribute to the wound healing process. There being few early stage macrophages within the chronic wound (mean 10.4, SD 6.7) (p≤0.01). Chronic wounds in comparison demonstrated a significant accumulation of tissue macrophages (mean 34.0, SD 10.5) when compared to acute wounds (mean 10.9, SD 4.4) with limited wound healing (p≤0.01). The dermagraft (DG) study comprising of 53 patients, showed that applying a biologically active dressing (1-12 dressings over 12 weeks) and compression to the wound bed, exhibited complete closure (76%) or reduction in the size of the wounds at 12 weeks, compared to compression alone. Changes in the extracellular components and an array of inflammatory cells and cytokines in fifty three paired wound bed biopsies (106) with and without DG were examined at week 0 and week 6 of treatment. On histological investigation, DG exhibited an increase in the amount of collagen present and angiogenesis in the wound at week 6 of treatment. Although there were no significant changes in the lymphocyte counts in response to the application of DG, it was possible to demonstrate a significant increase in the number of stage macrophages at week 6 of treatment (p≤0.05) and a significant reduction in the tissue macrophage counts, at week 6 of treatment (p≤0.05) in patients treated with 4 pieces of DG. The levels of different cytokine expression within the wound bed at week 6 exhibited some changes but this was not significant, in response to DG treatment. This could be to the possible presence of proteinases within the chronic wound bed hydrolysing the cytokines produced by DG. From the results attained, it was able to conclude, for clinical use 4 pieces of DG at regular dosing intervals were sufficient to achieve wound contraction or closure. This dose regimen has not been taken forward for further pivotal studies. This thesis thus represents some of the first evidence in human tissue that macrophages may play role in wound healing, and in chronic wounds, a subpopulation of macrophages can be modified to stimulate these wounds towards healing.