Black ceiling tiles reduce occupational UV exposure for staff in clinical area containing phototherapy cabinets.

Phototherapy clinics administer UV light to patients via phototherapy cabinets. The UV radiation from these cabinets reflects on the white ceiling tiles of the clinic and is directed towards both staff and patients in the area. This is particularly problematic for clinical technologists who must undertake dosimetry in these areas and have a particular time (often as low as 30 minutes) before they reach their maximum exposure limit. By replacing the white tiles with black alternatives which absorb the stray radiation, we have been able to reduce these reflections by almost 90%, prolonging the time to maximum exposure by nearly 10 times. We therefore present these findings to encourage similar clinics to undertake the simple protocols outlined which will significantly improve staff and patient safety.

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.

Significance: Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim: To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach: We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT's impact on brain tissue temperature. Results: The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J/cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 µM. Increases in treatment time and light power (light fluence = 400 J/cm2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 µM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer. Conclusions: With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.

Potential harm to the skin from unfiltered krypton chloride 'far-ultraviolet-C' lamps, even below an occupational exposure limit.

Ultraviolet-C (UVC) radiation can effectively inactivate pathogens on surfaces and in the air. Due to the potential for harm to skin and eyes, human exposure to UVC should be limited within the guideline exposure limits produced by the International Commission on Non-Ionising Radiation Protection (ICNIRP) or the American Conference of Governmental Industrial Hygienists (ACGIHs). Both organisations state an effective spectrally weighted limit of 3 mJ cm-2, although the spectral weighting factors of the two organisations diverged following a revision of the ACGIH guidelines in 2022. Using existing published human exposure data, the effective spectrally weighted radiant exposure was calculated for both unfiltered and filtered (to reduce UV emissions above 230 nm) krypton chloride (KrCl*) excimer lamps. The effective radiant exposure of the filtered KrCl* lamp was greater than 3 mJ cm-2when applying ICNIRP or either of the revised ACGIH spectral weightings. This indicates that both guidelines are appropriately conservative for this specific lamp. However, the effective radiant exposure of the unfiltered KrCl* lamp was as low as 1 mJ cm-2with the revised ACGIH weighting function that can be applied to the skin if the eyes are protected. Erythema has therefore been directly observed in a clinical study at an exposure within the revised ACGIH guideline limits. Extrapolating this information means that a mild sunburn could be induced in Fitzpatrick skin types I and II if that particular ACGIH weighting function were applied and an individual received an effective exposure of 3 mJ cm-2. Whilst it is improbable that such an effect would be seen in current deployment of KrCl* lamp technology, it does highlight the need for further research into skin sensitivity and irradiance-time reciprocity for UVC wavelengths.

Far-UVC (222 nm) efficiently inactivates an airborne pathogen in a room-sized chamber.

Many infectious diseases, including COVID-19, are transmitted by airborne pathogens. There is a need for effective environmental control measures which, ideally, are not reliant on human behaviour. One potential solution is Krypton Chloride (KrCl) excimer lamps (often referred to as Far-UVC), which can efficiently inactivate pathogens, such as coronaviruses and influenza, in air. Research demonstrates that when KrCl lamps are filtered to remove longer-wavelength ultraviolet emissions they do not induce acute reactions in the skin or eyes, nor delayed effects such as skin cancer. While there is laboratory evidence for Far-UVC efficacy, there is limited evidence in full-sized rooms. For the first time, we show that Far-UVC deployed in a room-sized chamber effectively inactivates aerosolised Staphylococcus aureus. At a room ventilation rate of 3 air-changes-per-hour (ACH), with 5 filtered-sources the steady-state pathogen load was reduced by 98.4% providing an additional 184 equivalent air changes (eACH). This reduction was achieved using Far-UVC irradiances consistent with current American Conference of Governmental Industrial Hygienists threshold limit values for skin for a continuous 8-h exposure. Our data indicate that Far-UVC is likely to be more effective against common airborne viruses, including SARS-CoV-2, than bacteria and should thus be an effective and "hands-off" technology to reduce airborne disease transmission. The findings provide room-scale data to support the design and development of effective Far-UVC systems.

Turn Up the Lights, Leave them On and Shine them All Around-Numerical Simulations Point the Way to more Efficient Use of Far-UVC Lights for the Inactivation of Airborne Coronavirus.

It has been demonstrated in laboratory environments that ultraviolet-C (UVC) light is effective at inactivating airborne viruses. However, due to multiple parameters, it cannot be assumed that the air inside a room will be efficiently disinfected by commercial germicidal ultraviolet (GUV) systems. This research utilizes numerical simulations of airflow, viral spread, inactivation by UVC and removal by mechanical ventilation in a typical classroom. The viral load in the classroom is compared for conventional upper-room GUV and the emerging "Far-UVC." In our simulated environment, GUV is shown to be effective in both well and poorly ventilated rooms, with greatest benefit in the latter. At current exposure limits, 18 commercial Far-UVC systems were as effective at reducing viral load as a single upper-room GUV. Improvements in Far-UVC irradiation distribution and recently proposed increases to exposure limits would dramatically increase the efficacy of Far-UVC devices. Modifications to current Far-UVC devices, which would improve their real-world efficacy, could be implemented now without requiring legislative change. The prospect of increased safety limits coupled with our suggested technological modifications could usher in a new era of safe and rapid whole room air disinfection in occupied indoor spaces.

Global verification of a model for determining daylight photodynamic therapy dose.

Daylight photodynamic therapy is an effective treatment for actinic keratoses and relies on a minimum PpIX-effective light exposure dose being delivered during treatment. As such, daylight dosimetry is an important aspect of this treatment. Relatively simple measurements of illuminance may be converted to PpIX-effective irradiance, and subsequently exposure dose, via a conversion model (the O'Mahoney model). This model has been verified against spectral irradiance data from the UK, however the accuracy of the model has not been determined outside the UK. In this work, we test the O'Mahoney model against spectral irradiance measurements from several global locations to within bounds of a median deviation of ±10 %. The median percentage deviations are shown to be independent of location latitude and longitude. The model can be used confidently to determine PpIX-effective irradiance from illuminance measurements irrespective of location and can be widely implemented as an effective and low-cost means of accurately measuring effective light exposure for this important treatment.

Extreme Exposure to Filtered Far-UVC: A Case Study†.

Far-UVC devices are being commercially sold as "safe for humans" for the inactivation of SARS-CoV-2, without supporting human safety data. We felt there was a need for rapid proof-of-concept human self-exposure, to inform future controlled research and promote informed discussion. A Fitzpatrick Skin Type II individual exposed their inner forearms to large radiant exposures from a filtered Krypton-Chloride (KrCl) far-UVC system (SafeZoneUVC, Ushio Inc., Tokyo, Japan) with peak emission at 222 nm. No visible skin changes were observed at 1500 mJ cm-2 ; whereas, skin yellowing that appeared immediately and resolved within 24 h occurred with a 6000 mJ cm-2 exposure. No erythema was observed at any time point with exposures up to 18 000 mJ cm-2 . These results combined with Monte Carlo Radiative Transfer computer modeling suggest that filtering longer ultraviolet wavelengths is critical for the human skin safety of far-UVC devices. This work also contributes to growing arguments for the exploration of exposure limit expansion, which would subsequently enable faster inactivation of viruses.

Development of a Predictive Monte Carlo Radiative Transfer Model for Ablative Fractional Skin Lasers.

It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50-400 mJ/pixel) from a CO2 AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

SmartPDT®: Smartphone enabled real-time dosimetry via satellite observation for daylight photodynamic therapy.

BACKGROUND: Actinic keratosis (AK) affects one quarter of over 60  year olds in Europe with the risk of transforming into invasive squamous cell carcinoma. Daylight photodynamic therapy (dPDT) is an effective and patient preferred treatment that uses sunlight to clear AK. Currently, there is no standardised method for measuring the light received during treatment. METHODS: SmartPDT® is a smartphone-based application and web-portal, developed by siHealth Ltd, enabling remote delivery of dPDT. It uses satellite imagery and computational algorithms to provide real-time determination of exposure to PpIX-effective solar radiation ("light dose"). The application also provides forecast of expected radiant exposures for 24- and 48-hs prior to the treatment period. Validation of the real-time and forecasted radiant exposure algorithms was performed against direct ground-based measurement under all weather conditions in Chilton, UK. RESULTS: Agreement between direct ground measurements and satellite-determined radiant exposure for 2-h treatment was excellent at -0.1 % ± 5.1 % (mean ±â€¯standard deviation). There was also excellent agreement between weather forecasted radiant exposure and ground measurement, 1.8 % ± 17.7 % at 24-hs and 1.6 % ± 25.2 % at 48-hs. Relative Root Mean Square of the Error (RMSEr) demonstrated that agreement improved as time to treatment reduced (RMSEr = 22.5 % (48 -hs), 11.2 % (24-hs), 5.2 % (real-time)). CONCLUSION: Agreement between satellite-determined, weather-forecasted and ground-measured radiant exposure was better than any existing published literature for dPDT. The SmartPDT® application and web-portal has excellent potential to assist with remote delivery of dPDT, an important factor in reducing risk in an elderly patient population during the Covid-19 pandemic.

Bring the Sunshine Indoors: Easy Dosimetry for Indoor Daylight Photodynamic Therapy.

Daylight photodynamic therapy (DPDT) is an effective and patient preferred treatment for the management of field change actinic keratosis. An important factor in DPDT is light dosimetry, to ensure that patients receive sufficient daylight for effective treatment, and this is the focus of the contribution to this issue by (La Rochelle et al. [2019] Photochem. Photobiol., https://doi.org/10.1111/php.13170). In this work, the authors present an easy-to-use method for obtaining real-time information about patient received light dose during treatment and for determining indoor locations best suited to DPDT.

Measuring Daylight: A Review of Dosimetry in Daylight Photodynamic Therapy.

Successful daylight photodynamic therapy (DPDT) relies on the interaction of light, photosensitisers and oxygen. Therefore, the 'dose' of light that a patient receives during treatment is a clinically relevant quantity, with a minimum dose for effective treatment recommended in the literature. However, there are many different light measurement methods used in the published literature, which may lead to confusion surrounding reliable and traceable dose measurement in DPDT, and what the most appropriate method of light measurement in DPDT might be. Furthermore, for the majority of practitioners who do not carry out any formal dosimetry and for the patients receiving DPDT, building confidence in the evidence supporting this important treatment option is of key importance. This review seeks to clarify the methodology of DPDT and discusses the literature relating to DPDT dosimetry.

Ultraviolet radiation exposure during daylight Photodynamic Therapy.

BACKGROUND: Daylight photodynamic therapy (dPDT) is an effective treatment for field-change actinic keratoses (AK), with similar efficacy to conventional PDT but lower patient pain scores. Whilst AK occur consequent to chronic solar ultraviolet (UV) exposure, paradoxically solar visible radiation is used during PDT. OBJECTIVES: To investigate the nature and levels of UV exposure, both erythemal UV and UVA, occurring during dPDT. METHODS: Four years of solar erythemally effective UV (UVE) irradiance, UVA irradiance and illuminance data were obtained from Pubic Health England for 12 locations. For a standard 2 h treatment period, the data were converted into standard erythemal doses (SEDs), UVA dose and protoporphyrin-IX (PpIX)-weighted dose from UVE irradiance, UVA irradiance and illuminance respectively. These three parameters were compared ascertaining the UV exposure received during dPDT. RESULTS: Analysis of UV exposure during dPDT showed a UK maximum average UVE exposure of 8.2 SED at Camborne (PpIX dose 23.4 J cm-2). Treatment earlier in the day reduces average UV exposure (Camborne 5.2 SED, PpIX dose 18.2 J cm-2), whilst PpIX dose achieves threshold during winter months (Camborne, November, 0.8 SED, PpIX dose 7.1 J cm-2). Cyprus and Gibraltar (with high UV exposure during dPDT) experience a maximum of 14.3 SED and 12.9 SED, with respective PpIX doses of 36.1 J cm-2 and 35.1 J cm-2, in June. UVA exposure is also presented for comparison. CONCLUSION: Therapeutically effective dPDT doses can be achieved at times of the day and year when UV exposure is minimal.

An investigation of different types of eyewear and face shields in protecting patients and operators from the harmful effects of ultraviolet radiation.

BACKGROUND: Phototherapy and photochemotherapy are commonly used treatment modalities for a range of chronic skin conditions. Whilst undergoing ultraviolet radiation exposure, patients can wear personal protective equipment. Face shields in combination with other forms of skin cover may be worn to provide both skin and eye protection. There are a number of different types of eyewear and face shields available for purchase. Some of these have clear identifications that show the levels of protection provided whilst others may not have any. METHODS: A series of similar experiments has been undertaken independently at two phototherapy treatment centres-Chapel Allerton Hospital, Leeds and Ninewells Hospital, Dundee-to investigate the effectiveness of different face shields and eye protection that are available for purchase in the United Kingdom (UK). Two similar examples of one face shield were tested at both centres, and another was transferred between the units. RESULTS: Not all examples of the face shields and protective eyewear provided the wearer full protection between 300 nanometres and 400 nanometres (nm). Cost and conformance to different standards was not always a good indicator. Some inexpensive examples tested also met British Association of Dermatology protective sunglasses guidelines. CONCLUSIONS: It is incumbent on all centres to check the properties of protective face shields and eyewear provided to patients and operators to guard against the effects from ultraviolet radiation. There is no correlation between price of the protective equipment and level of protection offered, and there may be opportunity for cost savings.

A novel light source with tuneable uniformity of light distribution for artificial daylight photodynamic therapy.

OBJECTIVES: Implementation of daylight photodynamic therapy (dPDT) is somewhat limited by variable weather conditions. Light sources have been employed to provide artificial dPDT indoors, with low irradiances and comparable treatment times to dPDT. Uniform light distribution across the target area is desirable in effective treatment planning, particularly for large areas. A novel light source is developed with tuneable direction of light emission in order to meet this challenge. METHODS: Wavelength composition of the novel light source is controlled such that the protoporphyrin-IX (PpIX) weighted spectra of both the light source and daylight match. The uniformity of the light distribution is characterised on a flat surface, a model head and a model leg. For context, a typical conventional PDT light source is also characterised. Additionally, the wavelength uniformity across the treatment site is characterised. RESULTS: The PpIX-weighted spectrum of the novel light source matches the PpIX-weighted daylight spectrum, with irradiance values within the bounds for effective dPDT. By tuning the direction of light emission, improvements are seen in the uniformity across large anatomical surfaces. Wavelength uniformity is discussed. CONCLUSIONS: We have developed a light source that addresses the challenges in uniform, multiwavelength light distribution for large area artificial dPDT across curved anatomical surfaces.

Quantifying Direct DNA Damage in the Basal Layer of Skin Exposed to UV Radiation from Sunbeds.

Nonmelanoma and melanoma skin cancers are attributable to DNA damage caused by ultraviolet (UV) radiation exposure. One DNA photoproduct, the cyclobutane pyrimidine dimer (CPD), is believed to lead to DNA mutations caused by UV radiation. Using radiative transfer simulations, we compare the number of CPDs directly induced by UV irradiation from artificial and natural UV sources (a standard sunbed and the midday summer Mediterranean sun) for skin types I and II on the Fitzpatrick scale. We use Monte Carlo radiative transfer (MCRT) modeling to track the progression of UV photons through a multilayered three dimensional (3D) grid that simulates the upper layers of the skin. By recording the energy deposited in the DNA-containing cells of the basal layer, the number of CPDs formed can be quantified. The aim of this work was to compare the number of CPDs formed in the basal layer of the skin and by implication the risk of developing cancer, as a consequence of irradiation by artificial and natural sources. Our simulations show that the number of CPDs formed per second during sunbed irradiation is almost three times that formed during solar irradiation.

Daylight photodynamic therapy in Scotland.

Chronic sun-induced dysplastic skin changes (actinic keratoses) are extremely common in fair-skinned people in Scotland. These changes are a major cause of morbidity and may develop into skin cancer. Actinic keratoses are often extensive and pose a therapeutic challenge as field-directed treatment is required for chronic disease management. One such treatment approach is hospital-based photodynamic therapy, which is a well-established treatment in Scotland for actinic keratoses, using a photosensitiser pro-drug and red LED light irradiation. However, photodynamic therapy using daylight as the activating light source is increasingly and effectively used in continental Europe, but had not been explored in Scotland until we initiated this in 2013. We report our experience of daylight photodynamic therapy in 64 patient-treatment courses and demonstrate that this can be an effective, well-tolerated treatment, which is liked by patients. Our most recent data show that most patients (73%) achieved clearance or at least a good response to treatment and had high levels of satisfaction with daylight photodynamic therapy. Daylight exposure measurements indicated that treatment is feasible in Scotland between April to September. Daylight photodynamic therapy is an important advancement in treatment options for Scottish patients with extensive pre-cancerous field changes and provides opportunities for home-based treatment and increased efficiency of photodynamic therapy services.

Black Hole in the Breast.

We report an unusual artifact, which was seen on a routine preoperative chest radiograph performed in a patient with breast cancer, before an elective mastectomy. Subsequently, this was identified to be secondary to a preoperative sentinel node injection. The report discusses the diagnostic dilemma caused by this artifact and raises the awareness of this possibility in patients undergoing these commonly performed procedures and investigations.