On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Genetic Association Analysis of Anti-VEGF Treatment Response in Neovascular Age-Related Macular Degeneration.

Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been FDA-approved in 2004, and since then has helped tens of thousands of patients worldwide to preserve vision. Still, treatment responses vary widely, emphasizing the need for genetic biomarkers to robustly separate responders from non-responders. Here, we report the findings of an observational study compromising 179 treatment-naïve nAMD patients and their reaction to treatment after three monthly doses of anti-VEGF antibodies. We show that established criteria of treatment response such as visual acuity and central retinal thickness successfully divides our cohort into 128 responders and 51 non-responders. Nevertheless, retinal thickness around the fovea revealed significant reaction to treatment even in the formally categorized non-responders. To elucidate genetic effects underlying our criteria, we conducted an undirected genome-wide association study followed by a directed replication study of 30 previously reported genetic variants. Remarkably, both approaches failed to result in significant findings, suggesting study-specific effects were confounding the present and previous discovery studies. Of note, all studies so far are greatly underpowered, hampering interpretation of genetic findings. In consequence, we highlight the need for an extensive phenotyping study with sample sizes exceeding at least 15,000 to reliably assess anti-VEGF treatment responses in nAMD.

Price and income effects of hospital reimbursements.

Health insurance systems in many countries reimburse hospitals through fixed prices based on the diagnosis-related groups (DRGs) of patients. We quantify the effects of price and income changes for the full spectrum of hospital services as average and heterogeneous elasticities of quantities (number of admissions) and quality-related outcomes. For our empirical analysis, we use data on over 160 million hospital admissions, constituting the universe of hospital admissions in Germany between 2005 and 2016. Our identification strategy is based on instruments exploiting a two-year lag in regulatory price setting. The strategy lends itself to a placebo test demonstrating that our instruments do not have substantive anticipatory direct effects. We find that the compensated own-price elasticity of quantity is positive (0.2), while the income elasticity is negative (-0.15). On net, increasing all prices increases costs due to a behavioral response of larger quantities in addition to the mechanical increase.

Pattern formation on the edge of chaos: experiments with CO oxidation on a Pt(110) surface under global delayed feedback.

Experiments with catalytic oxidation of carbon monoxide on Pt(110) show that chemical turbulence in this system can be suppressed by application of appropriate global delayed feedback. Different spatiotemporal patterns, seen near the transition from turbulence to uniform oscillations, are investigated. Such patterns include intermittent turbulence, oscillatory standing waves, cellular structures, and phase clusters. Using a method based on the Hilbert transform, spatial distributions of local phase and amplitude in these patterns are reconstructed from the experimental data.

Pattern formation during the CO-oxidation involving subsurface oxygen.

This paper focuses on subsurface oxygen and its influence on pattern formation during CO-oxidation on platinum surfaces. For the observation of spatiotemporal pattern formation during catalytic reactions the photoelectron emission microscope (PEEM) has proven to be an excellent real-time imaging instrument, capable of tracking local work function changes. The existence of subsurface oxygen on platinumlike surfaces has been extensively discussed and for palladium its presence has been clearly established during rate oscillations. Subsurface oxygen is defined at this point as an atomic O species located directly underneath the uppermost metal crystal layer; its dipole moment therefore considerably lowers the work function of the surface. Here we review some of the investigations involving subsurface oxygen, focusing on the role subsurface oxygen might play in pattern formation during CO-oxidation on platinum. We will also present some new results, where this species clearly interacts with chemisorbed oxygen under restrictions by boundary conditions on the Pt(110) single crystal. These previously (through microlithography) constructed domain boundaries on the surface are made out of Rh or Pd, and they are acting as an additional source of CO molecules for the Pt surface. (c) 2002 American Institute of Physics.

Front initiation on microdesigned composite catalysts.

We first briefly review the subject of spatiotemporal pattern formation on microdesigned composite catalysts. One of the most significant interaction mechanisms between different reacting domains (consisting of different metal catalysts such as Pt and Rh, coupled through surface diffusion) is the initiation of reaction fronts at the interface between them. We then explore in some detail the effect of two-dimensional composite geometry on this basic building block of composite catalyst dynamics. (c) 2002 American Institute of Physics.