[Regional variations in healthcare for patients with psoriasis and atopic dermatitis in Germany]. / Regionale Variationen in der Versorgung von Patienten mit Psoriasis und atopischer Dermatitis in Deutschland.

BACKGROUND: Psoriasis (Pso) and atopic dermatitis (AD) are chronic skin diseases that result in significant physical and psychological impairment, financial burden, and loss of quality of life. According to previous data, there are regional differences in healthcare. OBJECTIVES: The aim was to analyse the epidemiology as well as the treatment of insured people with Pso and AD in Germany in a regional comparison. METHODS: Data of the insurance company Techniker Krankenkasse for the year 2019 regarding treatment prevalences as well as drug prescriptions on the regional level for all physicians were examined. RESULTS: In 2019 the overall prevalence of Pso was 2.5% (about 2 million insured people in Germany) and AD was 4.2% (about 3.6 million insured people). In Pso, new guideline-compliant drugs were frequently utilised, yet systemic glucocorticosteroids (GCS) were still disproportionally prescribed. Regionally, there were pronounced disparities with higher prescription rates of the new drugs in the north and east. Insured people with AD most frequently received topical GCS (approx. 88%), of which most were class III (66%), and significantly less frequently calcineurin inhibitors (< 10%), which also conform to guidelines. Systemically, GCS were by far most commonly used (about 25% of all insured people with drug prescriptions). Dupilumab, the only long-term drug approved in 2019, was very rarely prescribed, accounting for less than 1%. Again, large regional differences similar to Pso were found. CONCLUSION: Pso and AD show relevant disparities and gaps in drug care in the regional comparison despite uniform national guidelines and patient needs. The barriers to appropriate modern pharmaceuticals need to be clarified and mitigated.

Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis.

Mitochondrial impairment induced by oxidative stress is a main characteristic of intrinsic cell death pathways in neurons underlying the pathology of neurodegenerative diseases. Therefore, protection of mitochondrial integrity and function is emerging as a promising strategy to prevent neuronal damage. Here, we show that pharmacological inhibition of hypoxia-inducible factor prolyl-4-hydroxylases (HIF-PHDs) by adaptaquin inhibits lipid peroxidation and fully maintains mitochondrial function as indicated by restored mitochondrial membrane potential and ATP production, reduced formation of mitochondrial reactive oxygen species (ROS) and preserved mitochondrial respiration, thereby protecting neuronal HT-22 cells in a model of glutamate-induced oxytosis. Selective reduction of PHD1 protein using CRISPR/Cas9 technology also reduced both lipid peroxidation and mitochondrial impairment, and attenuated glutamate toxicity in the HT-22 cells. Regulation of activating transcription factor 4 (ATF4) expression levels and related target genes may mediate these beneficial effects. Overall, these results expose HIF-PHDs as promising targets to protect mitochondria and, thereby, neurons from oxidative cell death.