Narrowband ultraviolet B treatment for psoriasis is highly economical and causes significant savings in cost for topical treatments

Background: Narrowband ultraviolet B (NB-UVB) treatment for psoriasis is considered expensive. However, existing data are based on estimates and do not consider indirect cost savings. Objectives: To define the actual costs of NB-UVB incurred by the service provider, as well as treatment-associated cost savings. Methods: We performed data linkage of (i) comprehensive treatment records and (ii) prescribing data for all NB-UVB treatment episodes spanning 6 years in a population of 420 000. We minimized data fluctuation by compiling data from four independent treatment sites, and using drug prescriptions unrelated to psoriasis as a negative control. Results: National Health Service Tayside spent an average of £257 per NB-UVB treatment course (mean 257 ± 63, range 150–286, across four independent treatment sites), contrasting sharply with the estimate of £1882 used by the U.K. National Institute for Health and Care Excellence. The cost of topical treatments averaged £128 per patient in the 12 months prior to NB-UVB, accounting for 42% of the overall drug costs incurred by these patients. This was reduced by 40% to £53 per patient over the 12-month period following NB-UVB treatment, while psoriasis-unrelated drug prescription remained unchanged, suggesting disease-specific effects of NB-UVB. The data were not due to site-specific factors, as confirmed by highly similar results observed between treatment sites operated by distinct staff. Finally, we detail all staff hours directly and indirectly involved in treatment, allowing direct translation of cost into other healthcare systems. Conclusions: NB-UVB is a low-cost treatment; cost figures currently used in health technology appraisals are an overestimate based on the data presented here. Creating or extending access to NB-UVB is likely to offer additional savings by delaying or avoiding costly third-line treatments for many patients.PostprintPeer reviewe

Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo

We have previously shown that peroxisome proliferator activating receptor ß/δ (PPAR β/δ is overexpressed in psoriasis. PPAR β/δ is not present in adult epidermis of mice. Targeted expression of PPAR β/δ and activation by a selective synthetic agonist is sufficient to induce an inflammatory skin disease resembling psoriasis. Several signalling pathways dysregulated in psoriasis are replicated in this model, suggesting that PPAR β/δ activation contributes to psoriasis pathogenesis. Thus, inhibition of PPAR β/δ might harbour therapeutical potential. Since PPAR β/δ has pleiotropic functions in metabolism, skin-targeted inhibition offer the potential of reducing systemic adverse effects. Here, we report that three selective PPAR β/δ antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for topical application to the skin and that their skin concentration can be accurately quantified using ultra-high performance liquid chromatography (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse model in reducing psoriasis-like changes triggered by activation of PPAR β/δ. PPAR β/δ antagonists GSK0660 and compound 3 do not exhibit systemic drug accumulation after prolonged application to the skin, nor do they induce inflammatory or irritant changes. Significantly, the irreversible PPAR β/δ antagonist (GSK3787) retains efficacy when applied topically only three times per week which could be of practical clinical usefulness. Our data suggest that topical inhibition of PPAR β/δ to treat psoriasis may warrant further exploration

Interrelations of vegetation growth and water scarcity in Iran revealed by satellite time series

Iran has experienced a drastic increase in water scarcity in the last decades. The main driver has been the substantial unsustainable water consumption of the agricultural sector. This study quantifies the spatiotemporal dynamics of Iran’s hydrometeorological water availability, land cover, and vegetation growth and evaluates their interrelations with a special focus on agricultural vegetation developments. It analyzes globally available reanalysis climate data and satellite time series data and products, allowing a country-wide investigation of recent 20+ years at detailed spatial and temporal scales. The results reveal a wide-spread agricultural expansion (27,000 km$^2$) and a significant cultivation intensification (48,000 km$^2$). At the same time, we observe a substantial decline in total water storage that is not represented by a decrease of meteorological water input, confirming an unsustainable use of groundwater mainly for agricultural irrigation. As consequence of water scarcity, we identify agricultural areas with a loss or reduction of vegetation growth (10,000 km$^2$), especially in irrigated agricultural areas under (hyper-)arid conditions. In Iran’s natural biomes, the results show declining trends in vegetation growth and land cover degradation from sparse vegetation to barren land in 40,000 km$^2$, mainly along the western plains and foothills of the Zagros Mountains, and at the same time wide-spread greening trends, particularly in regions of higher altitudes. Overall, the findings provide detailed insights in vegetation-related causes and consequences of Iran’s anthropogenic drought and can support sustainable management plans for Iran or other semi-arid regions worldwide, often facing similar conditions

Taking shortcuts: Cognitive conflict during motivated rule-breaking

Deliberate rule violations have typically been addressed from a motivational perspective that asked whether or not agents decide to violate rules based on contextual factors and moral considerations. Here we complement motivational approaches by providing a cognitive perspective on the processes that operate during the act of committing an unsolicited rule violation. Participants were tested in a task that allowed for violating traffic rules by exploiting forbidden shortcuts in a virtual city maze. Results yielded evidence for sustained cognitive conflict that affected performance from right before a violation throughout actually committing the violation. These findings open up a new theoretical perspective on violation behavior that focuses on processes occurring right at the moment a rule violation takes place

The influence of fractionated radiotherapy on the stability of spinal bone metastases: a retrospective analysis from 1047 cases

Background: The effect of radiotherapy, in particular the application of different multi-fraction schedules in the management of unstable spinal bone metastases (SBM), is incompletely understood. This study aims to compare the radiological response regarding various dose and fractionation schedules of radiotherapy in the palliative treatment of SBM. Methods: We retrospectively assessed 1047 patients with osteolytic SBM, treated with palliative radiotherapy at our department between 2000 and 2015. Lung cancer (40.2%), breast (16.7%) and renal cancer (15.2%) were the most common solid tumors in this study. Different common multi-fraction regimen (5x4Gy, 10x3Gy, 14 × 2.5Gy and 20x2Gy) were compared with regard to radiological response and recalcification at 3 and 6 months after radiotherapy. The Taneichi score was used for classification of osteolytic SBM. Results: Median follow up was 6.3 months. The median overall survival (OS) in the short-course radiotherapy (SCR) group using less than 10 treatment fractions was 5.5 months vs. 9.5 months in the long-course radiotherapy (LCR) group using in excess of 10 fractions (log rank p < .0001). Overall survival (OS) in the SCR group after 3 and 6 months was 66.8 and 49.1%, respectively vs 80.9 and 61.5%, respectively in the LCR group. 17.6% (n = 54/306) and 31.1% (n = 89/286) of unstable SBM were classified as stable in the SCR group at 3 and 6 months post radiotherapy, respectively (p < .001 for both). In the LCR group, 24.1% (n = 28/116) and 34.2% (n = 38/111) of unstable SBM were stabilized after 3 and 6 months, respectively (p < .001 for both). Conclusions: Our study shows no significant difference in stabilization achieving recalcification rates between multi-fraction schedules (SCR vs. LCR) in the palliative management of unstable SBM. Both groups with multi-fraction regimen demonstrate a stabilizing effect following 3 and 6 months after radiotherapy