No description available.

No description available.

Light-based therapies, including photodynamic therapy (PDT), for acne are gaining popularity in dermatology. Based largely upon in vitro data, their beneficial outcome in acne is thought to be related to their bactericidal effects on Propionibacterium acnes. This randomised controlled study sought to determine the efficacy and tolerability of 610-950 nm IPL (administered as IPL-Placebo) and IPL-assisted methyl aminolaevulinate PDT (IPL-MAL) vs. adapalene 0.1% gel in the treatment of acne and to identify their mode of action, looking specifically at the effect on surface density of P. acnes. Thirty seven patients (31% of target due to slow recruitment) with mild to moderate facial acne were randomly allocated to IPL-MAL treatment, IPL-Placebo or adapalene. Both IPL groups received four treatments to the whole face, 2 weeks apart, while the third group was given adapalene nightly for 12 weeks. Assessments performed at baseline and weeks 8, 11, and 16 included inflamed, noninflamed and total lesion counts, Leeds grading, follicular porphyrin fluorescence, the Family Dermatology Life Quality Index and Dermatology Life Quality Index scores, and patient’s perspective of clinical improvement by the visual analogue scale (VAS). Cutaneous microflora was collected from all patients at similar intervals. Of the 37 patients randomised, only 30 completed the trial (10 in each group) and were included in the final analyses. Adapalene was found to be significantly superior to IPL-MAL and IPL-Placebo in reducing the noninflamed (adapalene 37.6% vs. IPL-MAL 3.4% vs. IPL-Placebo −9.7%) and total lesion counts (adapalene 35.7% vs. IPL-MAL 4.3% vs. IPL-Placebo −8.4%) at week 16. This was accompanied by a significant decrease (52.9%) in the DLQI score in this group (p = 0.031). The maximum improvement in inflamed lesion counts from baseline was seen at week 11 in the IPL-MAL (20.7%) and IPL-Placebo (13.4%) groups but occurred at week 16 in the adapalene group (26.5%). Statistical significance, however, was not reached in any group. There was no significant difference within or between the groups in the VAS, Leeds, FDLQI and porphyrin fluorescence results pre- and post- treatment. A significant increase in the density of propionibacteria (p = 0.021) and xxi coagulase-negative staphylococci (p = 0.039) was seen in the IPL-Placebo and IPL- MAL groups at week 16 and week 8, respectively; however, there was no significant difference between the groups. All the treatments were well tolerated. Adapalene remains an effective first line treatment in mild to moderate facial acne. However, the present study has remained indecisive (due to being underpowered) in drawing any firm conclusions regarding the efficacy of IPL and IPL-MAL on inflamed acne lesions. Further research is therefore warranted before their use can be advocated for acne treatment. An alternative mode of action for IPL and IPL-assisted MAL-PDT other than photodynamic destruction of P. acnes is suggested from the results of this study.

Cutaneous squamous cell carcinoma (SCC) is a common cancer yet its treatment is under-researched. The objective of this thesis was to develop a proposal for a randomised controlled trial (RCT) to address uncertainties relating to the management of the condition, and to ultimately improve the management of affected patients. Two systematic reviews were initially conducted to appraise the current evidence base for SCC treatments. Only one RCT was eligible for inclusion in the Cochrane systematic review; a small study which found no significant difference in time to recurrence between patients treated with post-operative 13-cis retinoic acid and interferon, and those not receiving adjuvant treatment. Systematic review and meta-analysis of observational studies included 118 studies. Pooled estimates of recurrence were lowest after cryotherapy and curettage and electrodesiccation, although lesions treated by these modalities were mostly small and low-risk. Although pooled recurrence after Mohs surgery appeared lower than after conventional excision or radiotherapy, the differences were not significant with overlapping 95% confidence intervals. For photodynamic therapy, pooled recurrence after apparently successful initial treatment was particularly high (26%). Evidence relating to the effectiveness of topical and systemic treatments was very limited. Estimates of recurrence were used to inform the sample size calculation for the proposed RCT. A survey of healthcare professionals was conducted to establish research priorities and identify clinically important management uncertainties from which initial trial scenarios were formulated. High-risk SCCs were identified as a research priority, with optimal surgical management and the role of adjuvant radiotherapy being key areas of uncertainty. Through multi-disciplinary collaboration, a proposal for a two-stage RCT has been developed; in the first stage, locoregional recurrence after conventional surgery with a controlled excision margin will be compared with Mohs surgery, and in the second stage locoregional recurrence will be compared between patients treated with adjuvant radiotherapy versus those receiving no adjuvant treatment. Feasibility work conducted during the development of the trial has involved: a) A retrospective analysis of SCCs treated over twelve-months to determine the number of patients and types of SCCs potentially eligible for recruitment into the proposed trial and to further inform the sample size calculation. Within five years of treatment 6% of 357 patients experienced local recurrence, 3% had regional recurrence and 1.5% died of their SCC. Comparison of the most recent American Joint Cancer Council (AJCC7) and an alternative Brigham and Women’s Hospital (BWH) classification showed that approximately 50% of SCCs were T2 in both schemes and eligible for entry into the first stage of the proposed trial. However, an additional BHW T2b substage better stratified outcomes dependent on the number of risk features, and indicated that 19% of all SCCs would potentially be also eligible for the second stage of the trial. b) A questionnaire and focus group study to assess the acceptability of the RCT and to identify possible barriers to recruitment. Participants had a desire to be better informed about SCC, wanting information relating to the trial to be provided in a variety of formats. 71% of participants were hypothetically willing to be randomised into the surgical stage of the proposed trial but had more concerns about the second stage involving adjuvant radiotherapy. Lack of equipoise and confusion about the concept of randomisation will need to be carefully addressed when presenting the trial to participants. The proposed trial will be the first to directly compare treatments for the types of SCC seen commonly in clinical practice. For the trial to be adequately powered, an estimated 5400 participants will need to be recruited, so a multi-centre, multi-disciplinary approach will be necessary.

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This thesis discusses some aspects of the use of ultraviolet rays to treat skin disease. The early history of dermatological phototherapy in Scotland is summarised as an introduction to the more recent developments described in a chapter on the Scottish phototherapy and photochemotherapy audit of 1996/1997 (funded by the Clinical Resource and Audit Group, the Scottish Office). This audit revealed some aspects of the phototherapy service that could be improved, and identified areas of particular importance for future research. Firstly, what type of UVB phototherapy lamp is most effective: the narrow-band (311-313nm) TL-01 lamp, or the broad-band UVB lamp? A meta-analysis conducted as part of this thesis gave a clear answer. TL-01 UVB is much more effective than broad-band UVB. The second included study was a randomised, controlled study that has contributed to deciding the optimal treatment frequency for TL-01 UVB phototherapy of psoriasis. Although 5x weekly treatment cleared psoriasis slightly more quickly than 3x weekly treatment, the difference in speed of clearance was too small to warrant the significantly greater frequency of acute erythema during treatment, and the greater number of exposures and dose required. The final question, answered by a randomised, controlled trial, in conjunction with a systematic review of the previous literature, was: for chronic plaque psoriasis, is TL-01 UVB or psoralen-UVA photochemotherapy to be preferred? The study conducted for this thesis showed TL-01 UVB to be more effective. Heterogeneity in findings of the studies addressing this question highlighted the importance of the particular treatment regimens selected for comparison, but the overall conclusion was that TL-01 UVB is the first choice of these two therapies.

No description available.

No description available.

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