The use of illuminance as a guide to effective light delivery during daylight PDT in the UK

Background: Daylight PDT (dPDT) is an effective and nearly painless treatment for field-change actinic keratosis. Measuring the protoprophyrin-IX (PpIX)-weighted exposure dose can give an indication of when conditions are most viable for effective dPDT. It would be advantageous for practitioners if more detailed information of exposure dose and appropriate treatment conditions were available. Where sophisticated measurement equipment is unavailable, simpler and more cost-effective methods of dose measurement are desirable.Objectives: To devise a model whereby illuminance data can be converted into PpIX-weighted exposure dose, and to use this model to estimate appropriate times for dPDT across the UK and Ireland.Methods: Spectral irradiance data were analysed to obtain a conversion model for illuminance to PpIX-weighted dose. This model was applied to historic illuminance data from nine sites to obtain PpIX-weighted dose across the UK and Ireland. Temperature data and an analysis of conservatory-based dPDT were also considered.Results: A distribution of the expected PpIX-weighted dose across the nine locations is presented; however, the temperature data showed that it could be too cold for dPDT even when there is sufficient light exposure. Conservatory-based dPDT could extend the times in the year for possible treatment.Conclusions: This proposed conversion model provides a means of using an illuminance reading to calculate the PpIX-weighted exposure dose. Dosimetry of dPDT may be carried out simply and at low cost using the presented method, however the results presented may be used as a guide for those considering dPDT, without the need to conduct measurements themselves

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

Unsupervised White Matter Fiber Clustering and Tract Probability Map Generation: Applications of a Gaussian Process framework for White Matter Fibers

With the increasing importance of fiber tracking in diffusion tensor images for clinical needs, there has been a growing demand for an objective mathematical framework to perform quantitative analysis of white matter fiber bundles incorporating their underlying physical significance. This paper presents such a novel mathematical framework that facilitates mathematical operations between tracts using an inner product based on Gaussian processes, between fibers which span a metric space. This metric facilitates combination of fiber tracts, rendering operations like tract membership to a bundle or bundle similarity simple. Based on this framework, we have designed an automated unsupervised atlas-based clustering method that does not require manual initialization nor an a priori knowledge of the number of clusters. Quantitative analysis can now be performed on the clustered tract volumes across subjects thereby avoiding the need for point parametrization of these fibers, or the use of medial or envelope representations as in previous work. Experiments on synthetic data demonstrate the mathematical operations. Subsequently, the applicability of the unsupervised clustering framework has been demonstrated on a 21 subject dataset

The Adverse Effects of Topical Photodynamic Therapy:a consensus review and approach to management

Background: Topical photodynamic therapy (PDT) is widely used to treat superficial nonmelanoma skin cancer and dysplasia, and is generally well tolerated. However, as with all treatments, adverse effects may occur and awareness may facilitate approaches to prevention and management. Objectives: To review the available evidence relating to the adverse effects of topical PDT, to help inform recommendations in updated clinical guidelines produced by the British Association of Dermatologists and British Photodermatology Group, and the efficacy of preventative and therapeutic approaches.Methods: This review summarizes the published evidence related to the adverse effects of topical PDT and attempts to interpret this evidence in the context of patient risk and management.Results: Pain and discomfort during PDT are acute adverse effects, which can be minimized through the use of modified and low-irradiance PDT regimens and do not therefore usually limit successful treatment delivery. Other adverse effects include the risk of contact allergy to photosensitizer prodrugs, although this is rare but should be kept in mind, particularly for patients who have received multiple PDT treatments to larger areas. There are no other significant documented longer-term risks and, to date, no evidence of cumulative toxicity or photocarcinogenic risk.Conclusions: Topical PDT is usually well tolerated, reinforcing the utility of this important therapeutic option in dermatology practice. The main acute adverse effect of pain can typically be minimized through preventative approaches of modified PDT regimens. Other adverse effects are uncommon and generally do not limit treatment delivery.</p

Dyes, flies, and sunny skies: photodynamic therapy and neglected tropical diseases

Photodynamic therapy, in its various applications, represents the focused combination of electromagnetic radiation, a chemical (usually a dye) capable of its absorption and conversion, and oxygen to provide cytotoxicity (cell killing). The effect has been known for over a century, and there is considerable clinical use in terms of its application to various cancers. However, the antimicrobial properties of the technology, which are considerable, have received only a lukewarm reception by healthcare providers, and the possibilities for tropical disease therapy are mainly unexplored. This is particularly vexatious given both the inexpensive nature of the photosensitisers and light sources available and the lack of conventional forward progress in widespread diseases such as leishmaniasis, trypanosomiasis, and tuberculosis in the Developing World. The following review therefore covers the use, or potential use, of the photodynamic approach in this area, mainly with reference to tropical diseases having current ‘neglected’ status according to the World Health Organisation. © 2016 The Authors. Coloration Technology © 2016 Society of Dyers and Colourist

Pre-treatment with topical 5-fluorouracil increases the efficacy of daylight photodynamic therapy for actinic keratoses - A randomized controlled trial

BACKGROUND: Daylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance. This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses.METHODS: Sixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm2) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight.RESULTS: Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p&lt;0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p&lt;0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments.CONCLUSIONS: Sequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction.</p

Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I-III

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub-surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D-OCT) to characterize microvessels in AK I-III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I-III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D-OCT. On D-OCT, vessel shapes, -pattern and -direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D-OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty-seven patients with AK I-III (n = 207) and PD (n = 87) were included. Qualitative D-OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 μm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p &lt; 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non-specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p &lt; 0.001). Vessel direction changed in AK II-III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I-II than PD (p ≤ 0.025), whereas diameter remained constant. D-OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D-OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades.</p

A consensus on the use of daylight photodynamic therapy in the UK

Background: Actinic keratoses (AKs) are a consequence of chronic exposure to ultraviolet radiation. Treatment of chronically photo-damaged skin and AKs is driven by risk of progression to squamous cell carcinoma, as well as for symptomatic relief. Conventional photodynamic therapy (c-PDT) is indicated when AKs are multiple or confluent and if patients respond poorly or are unable to tolerate other therapies. c-PDT is limited by the field size that can be treated in single sessions and can cause significant discomfort.Objective: Recent studies investigated daylight illumination to activate protoporphyrin IX and daylight-PDT (d-PDT) is now licensed in the UK for face and scalp AKs. A group of experts met to discuss application of d-PDT with methyl aminolevulinate (MAL) and develop a UK consensus statement, specific to UK weather conditions.Methods: The UK consensus recommendations were reached among eight experts, who reviewed recent studies on d-PDT, assessed UK meteorological data and discussed personal experiences of d-PDT for AKs.Results: Recommendations from these discussions provide guidance on d-PDT use, specifically regarding patient selection, therapeutic indications, when to treat, skin preparation, MAL application and daylight exposure for patients with AKs.Conclusions: This UK expert consensus provides practical guidance for UK application of d-PDT

A chat about actinic keratosis:Examining capabilities and user experience of ChatGPT as a digital health technology in dermato-oncology

Background: The potential applications of artificial intelligence (AI) in dermatology are evolving rapidly. Chatbots are an emerging trend in healthcare that rely on large language models (LLMs) to generate answers to prompts from users. However, the factuality and user experience (UX) of such chatbots remain to be evaluated in the context of dermato-oncology. Objectives: To examine the potential of Chat Generative Pretrained Transformer (ChatGPT) as a reliable source of information in the context of actinic keratosis (AK) and to evaluate clinicians' attitudes and UX with regard to the chatbot. Methods: A set of 38 clinical questions were compiled and entered as natural language queries in separate, individual conversation threads in ChatGPT (OpenAI, default GPT 3.5). Questions pertain to patient education, diagnosis, and treatment. ChatGPT's responses were presented to a panel of 7 dermatologists for rating of factual accuracy, currency of information, and completeness of the response. Attitudes towards ChatGTP were explored qualitatively and quantitatively using a validated user experience questionnaire (UEQ). Results: ChatGPT answered 12 questions (31.6%) with an accurate, current, and complete response. ChatGPT performed best for questions on patient education, including pathogenesis of AK and potential risk factors, but struggled with diagnosis and treatment. Major deficits were seen in grading AK, providing up-to-date treatment guidance, and asserting incorrect information with unwarranted confidence. Further, responses were considered verbose with an average word count of 198 (SD 55) and overly alarming of the risk of malignant transformation. Based on UEQ responses, the expert panel considered ChatGPT an attractive and efficient tool, scoring highest for speed of information retrieval, but deemed the chatbot inaccurate and verbose, scoring lowest for clarity. Conclusions: While dermatologists rated ChatGPT high in UX, the underlying LLMs that enable such chatbots require further development to guarantee accuracy and concision required in a clinical setting.</p