A Review of Atomic-Force Microscopy in Skin Barrier Function Assessment.

Skin barrier function (SBF) disorders are a class of pathologies that affect a significant portion of the world population. These disorders cause skin lesions with intense itch, impacting patients' physical and psychological well-being as well as their social functioning. It is in the interest of patients that their disorder be monitored closely while under treatment to evaluate the effectiveness of the ongoing therapy and any potential adverse reactions. Symptom-based assessment techniques are widely used by clinicians; however, they carry some limitations. Techniques to assess skin barrier impairment are critical for understanding the nature of the disease and for helping personalize treatment. This review recalls the anatomy of the skin barrier and describes an atomic-force microscopy approach to quantitatively monitor its disorders and their response to treatment. We review a panel of studies that show that this technique is highly relevant for SBF disorder research, and we aim to motivate its adoption into clinical settings.

Assessment of adverse events for a home-use intense pulsed light hair removal device using postmarketing surveillance.

BACKGROUND AND OBJECTIVES: Home-use intense pulsed light (IPL) hair removal devices are convenient for consumers. Consumer safety associated with home-use IPL devices, however, remains a subject of interest. In this descriptive analysis, we assessed the most commonly reported adverse events (AEs) for a home-use IPL device from postmarketing surveillance and qualitatively compared these with AEs from clinical studies and medical device reports of home-use IPL treatments. MATERIALS AND METHODS: For this analysis of voluntary reports, we queried a distributor's postmarketing database for IPL devices for the period beginning January 1, 2016, to December 31, 2021. All sources of comments, for example, phone, e-mail, company-sponsored web sites, were included in the analysis. AE data were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Also, we conducted a PubMed search to identify AE profiles from existing literature on home-use IPL devices and we searched the Manufacturer and User Facility Device Experience (MAUDE) database for reports on home-use IPL devices. These results were qualitatively compared to the data in the postmarketing surveillance database. RESULTS: A total of 1692 cases involving IPL were identified from voluntary reports of AEs between 2016 and 2021. The shipment-adjusted reporting rate for AE cases (number of AE cases/100,000 shipped IPL devices) was 67/100,000 during this 6-year period. The most commonly reported AEs were pain of skin 27.8% (470/1692), "thermal burn" 18.7% (316/1692), and erythema 16.0% (271/1692). Among the top 25 AEs reported, no unexpected health events were observed. The reported AEs were qualitatively similar to the pattern seen in clinical studies and the MAUDE database associated with such home-use IPL treatments. CONCLUSION: This is the first such report documenting AEs for home-use IPL hair removal from a postmarketing surveillance program. These data are supportive of the safety of such home-use low-fluence IPL technology.

Dermatologic Scar Assessment With Stereoscopic Imaging and Digital Three-Dimensional Models: A Validation Study.

BACKGROUND AND OBJECTIVE: We evaluated a new handheld stereoscopic imaging system capable of visualizing scars with digital three-dimensional (3D) models and providing automated morphometric estimates. The objective was to validate the repeatability and accuracy of intra- and inter-investigator scan results. STUDY DESIGN/MATERIALS AND METHODS: Engineered metal plates with depressed and elevated model scars (n = 72) were scanned six times by one investigator. In vivo hypertrophic and atrophic scars (n = 15) were scanned once by three investigators. The repeatability of morphometric estimates was assessed using coefficients of variation (CVs) to compare the variation among multiple scan results for both models and in vivo scars, with 0% reflecting a perfect match. Scar estimates from digital 3D reconstructions were compared with the known dimensions of physical model scars and with ruler measurements of in vivo scars. RESULTS: A total of 48 model scars and 12 in vivo scars were eligible for automated analyses with the imaging system's proprietary software. Intra-investigator scan results for the model scars were repeatable, with low variance for all parameters: volume, area, length, and depth/height (CV: 1.8-3.1%). By comparison, inter-investigator scans of real in vivo scars resulted in slightly higher median CVs (4.4-7.3%; P < 0.05). 3D model scar estimates correlated well with the known physical dimensions of model scars for all parameters (P < 0.001) and accurately reflected the measurements of in vivo scars (P < 0.001). The six in vivo scars situated on the chest and abdomen showed the highest inter-investigator variation, due to respiratory movement artifacts. CONCLUSION: Stereoscopic imaging of scars generates accurate and repeatable measurement estimates that show little intra- and inter-investigator-based assessment variation. The best results are achieved by minimizing subject movement. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Noninvasive Assessment of Mycotic Nail Tissue Using an Ultraviolet Fluorescence Excitation Imaging System.

BACKGROUND AND OBJECTIVES: Mycological diagnosis of onychomycosis is based on direct microscopy using external fluorophores to visualize fungal tissue in nail samples and agar culture. Ultraviolet fluorescence excitation imaging (u-FEI) has shown potential in monitoring biological processes by exploiting variations in autofluorescence. This study aimed at assessing the potential of a handheld u-FEI system as a practical screening tool for fungal nail infections. STUDY DESIGN/MATERIALS AND METHODS: Ninety samples from 29 patients with microscopy-confirmed fungal infection and 10 control samples from healthy participants were collected (n = 100). Using a prototype u-FEI system (single bandpass 25 mm filter with a central pass wavelength of 340 nm and a bandwidth of 12 nm, 295 nm excitation flash, resolution of 640 × 480), images of all samples were acquired under standardized conditions. Average and maximum fluorescence intensity image values in arbitrary units (AU) of manually delineated regions of interests were quantitated and statistically assessed for significant differences between healthy and mycotic samples. RESULTS: UV-images clearly depicted all 100 nail samples, with a visibly stronger signal in infected samples. Statistically significant differences (P < 0.05) in signal intensity between mycotic samples and healthy controls were observed for maximum and average fluorescence values. Mean fluorescence values of onychomycotic samples showed 23.9% higher maximum (mycotic: 34.9 AU [standard deviation [SD] 4.7]; healthy: 28.2 AU [SD 1.9]) and 10.2% higher average (mycotic: 27.6 AU [SD 2.0]; healthy: 25.0 AU [SD 0.7]) signal intensity values. Receiver operating characteristic curves demonstrated excellent discriminatory ability (area under the curve > 0.9). Analysis of fluorescence measurements of the reference standard demonstrated very low variation (coefficient of variation = 0.62%) CONCLUSION: Quantitation of u-FEI intensities enables differentiation between healthy and mycotic nail samples, constituting a potential point-of-care tool for cost-effective screening for onychomycosis at a primary care level. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Criteria for site selection in industry-sponsored clinical trials: a survey among decision-makers in biopharmaceutical companies and clinical research organizations.

BACKGROUND: Knowledge of what the pharmaceutical industry emphasizes when assessing trial sites during site selection is sparse. A better understanding of this issue can improve the collaboration on clinical trials and increase knowledge of how to attract and retain industry-sponsored trials. Accordingly, we investigated which site-related qualities multinational biopharmaceutical companies and clinical research organizations (CROs) find most important during site selection. METHODS: An online survey among decision-makers for trial site selection in the Nordic countries employed at multinational biopharmaceutical companies and CROs was conducted. The respondents' experiences with and perceptions of site selection were addressed to evaluate the relative importance of site-related qualities. We included up to four respondents per company, representing different geographic regions. Descriptive statistics were used to summarize findings. RESULTS: Of 49 eligible companies, 20 biopharmaceutical companies and 23 CROs participated. In total, 83 responses were analyzed (estimated response rate 78%). A relative importance of site-related qualities was identified: For example, 88% (binomial 95% confidence interval [CI] ±7%) preferred reaching enrollment goals at trial sites in their region 10% quicker rather than cutting the costs at all sites by 20%. Likewise, 42% (CI ±11%) of the respondents preferred that trial sites were best at having the first patients ready for inclusion right after site initiation visit compared to having good data entry, documentation, and reporting practice (25% [CI ±9%]), easily reachable site personnel and backup (23% [CI ±9%]), fast contractual procedure times (6% [CI ±5%]), a key opinion leader associated with the site (3% [CI ±4%]), and updated equipment and facilities (1% [CI ±2%]). In total, 75% [CI ±9%] agreed that their company would be interested in cooperating with an inexperienced trial site if the site had access to a large patient population and 52% [CI ±11%] had experienced that their company selected an inexperienced trial site in favor of an experienced site due to a higher level of interest and commitment. CONCLUSIONS: This study indicates that recruitment-related factors are pivotal to the pharmaceutical industry when assessing trial sites during site selection. Data quality-related factors seem highly valued especially in early phase trials whereas costs and investigator's publication track record are less important. Experience in conducting clinical trials is not imperative. However, this applies primarily to late phase trials.

New lasers and light sources - old and new risks?

Recent developments (new wavelengths, treatment concepts, and combinations) in the field of lasers, intense pulsed light (IPL), LED, as well as new energy and light sources have opened up new therapeutic options that extend beyond mere aesthetic indications. Thus, while fractional lasers used to be employed to merely treat wrinkles, the same devices - in the context of laser-assisted drug delivery - have now become important tools in the treatment of scars, field cancerization, and epithelial tumors. The requirements posed to physicians, both with respect to establishing the indication and conducting treatment, have been growing along with the increase in technological complexity as well as the rising number of comorbidities and comedications in a patient population that continues to age. At the same time, home-use devices have been introduced for a variety of indications. These devices are characterized by low power and special safety features aimed at preventing accidents, risks, and side effects. Despite the reduced efficacy of such self-treatment devices, there is an increased risk of misuse, given that the basic prerequisite for adequate treatment cannot be ensured, to wit, the exact diagnosis and therapeutic indication. Consequently, during hair removal or anti-wrinkle treatment, pigmented lesions and cutaneous neoplasms may be altered, thus giving rise to expected, unexpected and new side effects and complications. In the aforementioned setting, it is important that all potential users of these new technologies be properly trained in a manner that ensures those treated a maximum of safety and efficacy in accordance with the guiding principle "diagnosis certa - ullae therapiae fundamentum".

[Dermatologic laser surgery].

In this article we give an overview of which skin conditions that are currently treated with laser and explains the basic principles of treatment. In addition, we summarize recommendations of the Danish Dermatological Society for demarcation of medical treatments which can be provided free of charge from cosmetic self-payment treatments.

Fractional CO2 laser treatment of caesarean section scars-A randomized controlled split-scar trial with long term follow-up assessment.

BACKGROUND AND OBJECTIVES: Caesarean section (c-section) scars can be pose functional and cosmetic challenges and ablative fractional laser (AFXL) treatment may offer benefit to patients. We evaluated textural and color changes over time in AFXL-treated versus untreated control scars. MATERIALS AND METHODS: A randomized, controlled, intra-individual split-scar trial with three sessions of AFXL-treatments for mature c-section scars. Settings of AFXL were adjusted to each individual scar. End-points were blinded on-site clinical evaluations at 1, 3, and 6 months follow-up (Patient and Observer Scar Assessment Scale [POSAS] and Vancouver Scar Scale [VSS]), blinded photo-evaluations, reflectance measurements, tissue histology, and patients satisfaction. RESULTS: Eleven of 12 patients completed the study. At 1 month follow-up, AFXL-treated scars were significantly improved in pliability (POSAS P = 0.01 VSS P = 0.02) and smoother in surface relief (POSAS P = 0.03) compared to control scars. At 1-3 months, overall scar appearance was dominated by transient erythema and hyperpigmentation, confirmed by reflectance measurements (erythema% and pigmentation% peaked at 1 and 3 month follow-up, respectively). At 6 months follow-up, AFXL-treated scars improved on POSAS-total score though not significantly (P = 0.06). Correspondingly, blinded photo-evaluation found AFXL-treated scars significantly improved compared to controls (VAS P = 0.02). Histology indicated new dermal collagen and elastic fibers on AFXL-treated scars. At 6 months follow-up, a majority of patients (64%) favored subsequent AFXL-treatment of their untreated control scar tissue. CONCLUSIONS: Scar remodeling is initiated 1 month after AFXL treatment, but overall scar improvement is concealed until laser-induced color changes resolve. At 6 months follow-up, the benefit of AFXL treatment on c-section scars emerges. Lasers Surg. Med. 49:189-197, 2017. © 2016 Wiley Periodicals, Inc.

Non-ablative fractional laser provides long-term improvement of mature burn scars--a randomized controlled trial with histological assessment.

BACKGROUND AND OBJECTIVES: Non-ablative fractional laser-treatment is evolving for burn scars. The objective of this study was to evaluate clinical and histological long-term outcome of 1,540 nm fractional Erbium: Glass laser, targeting superficial, and deep components of mature burn scars. MATERIALS & METHODS: Side-by-side scar-areas were randomized to untreated control or three monthly non-ablative fractional laser-treatments using superficial and extra-deep handpieces. Patient follow-up were at 1, 3, and 6 months. Primary outcome was improvement in overall scar-appearance on a modified-Patient-and-Observer-Scar-Assessment-Scale (mPOSAS, 1 = "normal skin", 10 = "worst imaginable scar"). Secondary outcomes included histology, patient satisfaction (0-10), patient-assessed improvement, and safety. RESULTS: Study was completed by 17 of 20 randomized patients with normotrophic (n = 11), hypertrophic (n = 5) or atrophic (n = 1) scars. Scar-appearance improved from laser-treatments (P < 0.001 vs. untreated) and histology at 6 months supported collagen-remodeling. Improvement appeared continuously during the post-operative period (mPOSAS baseline: 7 [5-8], 6 months: 4 [3-5] P = < 0.001). At 6 months, patients were satisfied with treatment (6 [3-9]) and 82% reported improved scar-texture. Treatments caused mild to moderate pain (4 [2-7]). Adverse effects decreased during follow-up and at final assessment, discrete erythema, hyperpigmentation or imprints from laser-grid were present in 11 patients. No patients experienced worsening of scar-appearance. CONCLUSIONS: Combined superficial and deep non-ablative fractional laser-treatments induce long-term clinical and histological improvement of mature burn scars.

Itch severity and quality of life in patients with pruritus: preliminary validity of a Danish adaptation of the itch severity scale.

The aim of this study was to examine the validity of a Danish adaptation of the Itch Severity Scale (ISS) by exploring the associations between pruritus severity, psychological symptoms, and quality of life in a consecutively recruited sample of 20 patients with atopic dermatitis, 20 with psoriasis, 20 with urticaria, 12 with genital pruritus, 11 with nephrogenic pruritus, and 20 controls with vascular malformations. Convergent and discriminative validity was explored by analysing the associations of the ISS total score and the individual ISS component scores with age, sex, diagnosis, disease severity, sleep quality, depressive symptoms, anxiety, non-specific somatic symptoms, and pruritus-related quality of life impairment. Patients with urticaria reported significantly (p < 0.05) greater pruritus severity scores than the remaining patient groups, and pruritus severity was significantly associated with impaired sleep quality, more depressive symptoms, higher levels of anxiety, more non-specific somatic symptoms, and impaired quality of life. The results also confirmed the multidimensional nature of pruritus, with the affective dimension of pruritus being a better predictor of depressive symptoms, anxiety, and quality of life impairment than the sensory dimension. Finally, our results confirmed previous findings that the associations between pruritus severity and depressive symptoms and somatic symptoms were partly mediated by the effect of pruritus on sleep quality.

[Free versus non-free treatments with laser and intense pulsed light in dermatology: distinguishing medical laser treatments to be provided free of charge from cosmetic self-payment treatments]. / Dermatologisk behandling med laser og intenst pulserende lys: afgraensning af medicinske vederlagsfri versus kosmetiske ikkevederlagsfri behandlinger.

Lasers and light sources are increasingly used in dermatology. Due to the limited financial resources of the public health care system, the Danish Dermatological Society has developed recommendations for distinguishing medical laser treatments to be provided free of charge from cosmetic self-payment treatments. Several considerations underlie the recommendations: present legislation; the diagnosis, etiology, severity, and anatomical location of the disease; and the availability of evidence-based treatments. It is suggested that the recommendations constitute the basis for referring patients to dermatological treatment involving laser and intense pulsed light in Denmark.