A Prospective Study to Evaluate the Impact of Golimumab Therapy on Work Productivity and Activity, and Quality of Life in Patients With Rheumatoid Arthritis, Psoriasis Arthritis and Axial Spondyloarthritis in a Real Life Setting in AUSTRIA. The GO-ACTIVE Study.

Objective: To analyze real-world evidence on work productivity and daily activity impairment (WPAI) and health-related quality of life (HRQoL) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients treated with golimumab in Austria. Methods: This was a prospective, non-interventional, multi-center study conducted in RA, PsA and axSpA patients initiating golimumab between April 2016 and May 2020 in 40 centers in Austria. WPAI, HRQoL (RAQoL, ankylosing spondylitis (AS)QoL and PsAQoL) questionnaires and disease activity (Clinical Disease Activity Index, CDAI, in RA and PsA; Bath Ankylosing Spondylitis Disease Activity Index, BASDAI, in axSpA) were assessed at baseline and months 3, 6, 12, 18, and 24. Association between WPAI and disease activity was tested using linear regression. Results: We enrolled 233 patients (RA, n = 95; axSpA, n = 69; PsA, n = 69), 110 patients were followed up to month 24. Mean age was 50.2 ± 14.2 years; 64% were female. Disease activity decreased from baseline to month 24 (RA: CDAI -24.3 ± 13.5; axSpA: BASDAI -4.4 ± 2.1, and PsA: CDAI -21.7 ± 8.5, p < 0.0001, each). Total work productivity impairment (TWPI), activity impairment and presenteeism subscores continuously decreased throughout month 24 in all indications: RA (-58.3 ± 23%, -62.6 ± 23.8% and -61.7 ± 23.3%, respectively as compared to baseline; p < 0.0001, each), axSpA (-34.4 ± 38.3%, p = 0.0117; -60.9 ± 25.9%, and -43.8 ± 26.6%, respectively, p ≤ 0.0001 both) and PsA (-35.8 ± 43.7%, p = 0.0186; -52.3 ± 25.4%, p < 0.0001; and -43.3 ± 33.5%, p = 0.0007, respectively). Absenteeism scores decreased only in RA patients (-9.2 ± 24.9%, p = 0.0234). HRQoL improved between baseline and month 24 (RAQoL: -12.6 ± 7.5; ASQoL: -8.0 ± 4.3; PsAQoL; -8.3 ± 6.4, p < 0.0001, each). TWPI, presenteeism and activity impairment strongly associated with disease activity throughout the study. Conclusions: This real-world study confirms the benefit of golimumab on work productivity/daily activity impairment in Austrian RA, PsA, and axSpA patients.

Efficiency benchmarks in the surgical management of primary rhegmatogenous retinal detachment: a monocentric register cohort study of operating room time metrics and influential factors.

OBJECTIVES: To investigate the effect of clinical, methodological and logistic factors on operating room (OR) efficiency in the surgical management of primary rhegmatogenous retinal detachment (RRD). DESIGN: Monocentric retrospective register cohort study. SETTING: Single tertiary centre in the western region of Austria. PARTICIPANTS: We audited patients diagnosed with primary RRD who were treated between January 2014 and August 2019. In total, 783 eyes of 776 consecutive patients were included in this study. Various risk factors affecting OR time efficiency and anatomical success after pars plana vitrectomy (PPV) procedures and scleral buckle (SB) surgery were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: OR efficiency was the primary outcome measure. Secondary outcome measures were the primary success rate after PPV procedures and SB surgery. RESULTS: PPV was performed in 641 (81.9%) eyes and SB surgery in 142 (18.1%) eyes. Mean surgical times in PPV and SB under retrobulbar anaesthesia (RA) were 74.0 (±32.6) min and 62.1 (±24.6) min (p<0.001), respectively, while under general anaesthesia (GA), these values were 112.0 (±52.0) min and 76.0 (±22.5) min (p<0.001), respectively. A regression analysis revealed the following main risk factors for prolonged OR time for the surgical management of RRD with PPV (all p<0.001): presence of a giant tear (ß=24.01; 32%), proliferative vitreoretinopathy (PVR)-C (ß=16.43; 22%), surgery postponed for 72 hours after diagnosis (ß=21.40; 29%), GA (ß=23.64; 32%) or surgery performed by a trainee (ß=17.35; 23%). PVR (p=0.022) in PPV cases, after-hours settings (p=0.006) and surgeon experience (p=0.030) in SB cases were independent risk factors for reduced success rates. CONCLUSIONS: OR coordinators should consider various independent clinical (giant tear, PVR-C, advanced detachment), methodological (PPV vs SB) and logistic (GA vs RA, after-hours setting and surgeon experience) factors to improve the success rate and surgical management planning of RRD accurately while optimising OR resources and staff efficiency.

Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism.

PURPOSE: To analyse the effect of intravitreal aflibercept injections on systemic angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration (nAMD). METHODS: In a prospective, randomized study, aflibercept (2.0 mg/50 µl) or ranibizumab (0.5 mg/50 µl) was administered intravitreally to 38 treatment-naive patients. Blood samples were taken before, 7 days after, and 28 days after the first intravitreal therapy. Cytokine levels were measured by enzyme-linked immunosorbent assay. Twenty-two age- and sex-matched individuals served as controls. RESULTS: At baseline, there were no significant differences of systemic Ang2 and VEGF-A levels among the treatment and control groups. After intravitreal aflibercept administration, median (interquartile range: IQR) systemic Ang2 was significantly upregulated from 1819 pg/ml (1262-3099) to 2123 pg/ml (1441-3769; p = 0.011) 7 days after the drug injection and remained non-significantly elevated at 1944 pg/ml (1431-2546 pg/ml; p = 0.653) 28 days after the drug injection. Median (IQR) systemic VEGF-A levels were significantly reduced from 43 pg/ml (30-57) to 8 pg/ml (8-8; p < 0.0001) 7 days and 16 pg/ml (8-26; p = 0.001) 28 days after the injection in the aflibercept group. There were no significant effects on systemic VEGF-A and Ang2 levels in the ranibizumab group at any time point following the first injection. CONCLUSION: In this study, we report significant systemic upregulation of Ang2 after intravitreal aflibercept administration. This counterregulatory response may represent a potential escape mechanism from antiangiogenic therapy.

[Diagnosis, treatment and monitoring of diabetic eye disease (Update 2019)]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung (Update 2019).

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow-up depending on stage of diabetic eye disease are summarized.

EFFECT OF PATIENTS' CLINICAL INFORMATION ON THE DIAGNOSIS OF AND DECISION TO TREAT RETINOPATHY OF PREMATURITY.

PURPOSE: To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS: Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS: A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION: These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.

[Diagnosis, treatment and monitoring of diabetic eye control]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung.

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow up depending on stage of diabetic eye disease are summarized.

Inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity.

PURPOSE: To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). DESIGN: Prospective intra- and inter-rater reliability analysis. METHODS: In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. RESULTS: Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0-5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). CONCLUSIONS: ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.

A randomised double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration.

AIM: The current accepted standard treatment for neovascular age-related macular degeneration (AMD) consists of antivascular endothelial growth factor agents including ranibizumab and bevacizumab. The aim of the study was to examine whether bevacizumab is inferior to ranibizumab with respect to maintaining/improving visual acuity. METHODS: In this prospective randomised parallel group multicentre trial patients aged more than 50 years with treatment naive nAMD were included at 10 Austrian centres. Patients were randomised to treatment either with 0.5 mg ranibizumab or 1.25 mg bevacizumab. Both groups received three initial monthly injections and thereafter monthly evaluation of visual acuity and the activity of the lesion. Re-treatment was scheduled as needed. Outcome measures were early treatment of diabetic retinopathy visual acuity, retinal thickness, lesion size and safety evaluation. RESULTS: A total of 321 patients were recruited of which four had to be excluded due to different reasons. Of the 317 remaining patients 154 were randomised into the bevacizumab group and 163 into the ranibizumab group. At month 12, there was a mean increase of early treatment of diabetic retinopathy visual acuity of 4.9 letters in the bevacizumab and 4.1 letters in the ranibizumab group (p=0.78). Furthermore, there were no significant differences in the decrease of retinal thickness, change of lesion size and number of adverse events between the groups. CONCLUSIONS: Bevacizumab was equivalent to ranibizumab for visual acuity at all time points over 1 year. There was no significant difference of decrease of retinal thickness or number of adverse events.

[Diagnosis, therapy and follow up of diabetic eye disease]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung.

Diabetes mellitus causes diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of the metabolic control. The recommendations of the Austrian Diabetes Association for the diagnosis, the therapeutic procedures and requirements for adequate follow up depending on the stages of the different forms of diabetic eye disease are summarized.

Mitochondrial haplogroups and control region polymorphisms in age-related macular degeneration: a case-control study.

BACKGROUND: Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA) are postulated to be susceptibility factors for this disease. Previous studies from Australia and the United States detected associations of mitochondrial haplogroups with AMD. The aim of the present study was to test these associations in Middle European Caucasians. METHODOLOGY/PRINCIPAL FINDINGS: Mitochondrial haplogroups (combinations of mtDNA polymorphisms) and mitochondrial CR polymorphisms were analyzed in 200 patients with wet AMD (choroidal neovascularization, CNV), in 66 patients with dry AMD, and in 385 controls from Austria by means of multiplex primer extension analysis and sequencing, respectively. In patients with CNV, haplogroup H was found to be significantly less frequent compared to controls, and haplogroup J showed a trend toward a higher frequency compared to controls. Five CR polymorphisms were found to differ significantly in the two study populations compared to controls, and all, except one (T152C), are linked to those haplogroups. CONCLUSIONS/SIGNIFICANCE: It can be concluded that haplogroup J is a risk factor for AMD, whereas haplogroup H seems to be protective for AMD.

Encapsulated inorganic nanostructures: a route to sizable modulated, noncovalent, on-tube potentials in carbon nanotubes.

The large variety of hybrid carbon nanotube systems synthesized to date (e.g., by encapsulation, wrapping, or stacking) has provided a body of interactions with which to modify the host nanotubes to produce new functionalities and control their behavior. Each, however, has limitations: hybridization can strongly degrade desirable nanotube properties; noncovalent interactions with molecular systems are generally weak; and interlayer interactions in layered nanotubes are strongly dependent upon the precise stacking sequence. Here we show that the electrostatic/polarization interaction provides a generic route to designing unprecedented, sizable and highly modulated (1 eV range), noncovalent on-tube potentials via encapsulation of inorganic partially ionic phases where charge anisotropy is maximized. Focusing on silver iodide (AgI) nanowires inside single-walled carbon nanotubes, we exploit the polymorphism of AgI, which creates a variety of different charge distributions and, consequently, interactions of varying strength and symmetry. Combined ab initio calculations, high-resolution transmission electron microscopy, and scanning tunneling microscopy and spectroscopy are used to demonstrate symmetry breaking of the nanotube wave functions and novel electronic superstructure formation, which we then correlate with the modulated, noncovalent electrostatic/polarization potentials from the AgI filling. These on-tube potentials are markedly stronger than those due to other noncovalent interactions known in carbon nanotube systems and lead to significant redistribution of the wave function around the nanotube, with implications for conceptually new single-nanotube electronic devices and molecular assembly. Principles derived can translate more broadly to relating graphene systems, for designing/controlling potentials and superstructures.

Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age-related macular degeneration.

PURPOSE: To determine whether different complement factor H (CFH) genotypes play a role in treatment of age-related macular degeneration (AMD) with intravitreal bevacizumab. METHODS: In this prospective study, we included 197 patients with exudative AMD and treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. In all patients, ophthalmological examinations, visual acuity, optical coherence tomography (OCT), fundus photography and fluorescein angiography were performed. Single nucleotide polymorphism (SNP) genotyping was performed using restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products. RESULTS: Age, gender and baseline mean visual acuity were similar among the three CFH genotypes. There was no significant difference in underlying lesion type of CNV, lesion size, number of injections or macula thickness. When examining the effect of genotype on post-treatment visual acuities, we observed a significant worse outcome for distance and reading visual acuity in the CFH 402HH genotype group. The number of patients who lost 3 or more lines in distance and reading visual acuity testing was significantly higher in the CFH 402HH (41%, 46%) genotype group than in patients with the CFH 402YY (28%, 26%) and CFH 402YH (26%, 24%) genotype. CONCLUSIONS: In addition to the higher risk for exudative AMD in patients with the CFH 402HH genotype that was found in previous studies, our results show that the CFH 402HH genotype also correlates with lower visual acuity outcome after treatment with bevacizumab, suggesting that pharmacogenetics of CFH plays a role in response to treatment of wet AMD.

Safety and feasibility of a novel intravitreal tamponade using a silicone oil/acetyl-salicylic acid suspension for proliferative vitreoretinopathy: first results of the Austrian Clinical Multicenter Study.

BACKGROUND: The safety and efficacy of a new surgical method of intravitreal tamponade using silicone oil suspended with aspirin (acetylsalicylic acid) was investigated for the treatment of proliferative vitreoretinopathy. METHODS: The study was designed as a prospective, randomized, controlled, double-blind multicenter study. A total of 29 patients were included; 15 patients were treated with the silicone oil suspended with aspirin, and 14 patients represented the control group receiving only silicone oil. A standard three-port pars plana vitrectomy was performed in 29 eyes of 29 patients. In cases in which the natural lens was present, simultaneous phacoemulsification was required. The control group received as standard therapy a vitreous tamponade with pure 5000 mPas silicone oil and the treatment group received silicone oil containing 0.2 mg/ml aspirin (AS SiO). At 6 months after surgery, the tamponade was removed from all eyes. The main outcome measure was the incidence of retinal redetachment requiring reoperation. Secondary outcome measures were visual acuity and ophthalmic examination results. RESULTS: The rate of redetachment, defined as the primary outcome parameter, was the same for both groups. The AS SiO was well tolerated and remained clear during the 6-month study period. Clinical examination revealed no signs of local or systemic adverse effects. The visual acuities were well matched before inclusion in the study and there were no significant differences during the follow-up period and in the final visual outcome between the two groups. CONCLUSIONS: Aspirin delivery by intravitreal silicone oil in the human eye is safe and also may provide a delivery vehicle for other antiproliferative agents to the posterior pole.

Self-assembled molecular nanowires of 6,13-Bis(methylthio)pentacene: growth, electrical properties, and applications.

We demonstrate a comprehensive study of self-assembled molecular nanowire, including molecular design, one-dimensional crystal growth, resistivity measurement of individual wire, and application to a field-effect transistor. Appropriate molecular design and control of interfacial interactions lead to single crystalline wire growth with an extensive pi-stacking motif. Resistivity measurements of an individual molecular wire indicate that these structural features are advantageous for electrical transport. Finally, field-effect transistors with single- and double-wire channels were fabricated to give some indication of the potential application of the molecular wires.

Integration of individual nanoscale structures into devices using dynamic nanostenciling.

We succeeded in integrating individual, pre-existing nanostructures into functional devices using ultrahigh vacuum dynamic nanostenciling and show working devices based on single-walled carbon nanotubes, a benchmark nanomaterial, and porphyrin J-aggregates, a "soft" supramolecular nanomaterial. Nanostructures are first located via atomic force microscopy, while device elements are added step by step, with an achieved positional accuracy of 20 nm, using a shadow mask assembly that moves while being exposed to evaporated material. Electronic transport, potentiometry, and scanning Kelvin probe were used for control at any fabrication stage and were available in situ. Such complex fabrication/characterization capabilities, applicable repeatedly, reliably, and nondestructively, pave the way for dynamic nanostenciling instrumentation to establish itself as a viable tool for easy integration and prototyping of fragile nanostructures synthesized through a wide range of processes.

[Requirements of a regional medical service for drug addicted patients]. / Anforderungen an ein regionalisiertes medizinisches Versorgungssystem für Drogenabhängige.

Modern services for persons with disorders resulting from psychoactive drug abuse must conform to the complexity of their needs. Low threshold access, standards for the prescription of opiates, out-patient, in-patient and day-hospital detoxification, rehabilitation and abstinence oriented strategies are fundamental prerequisites. The quality of services for drug dependent patients is defined by the percentage finding access to the service, the percentage of those continuing in the service, the easy and rapid transition between the different elements of the service, the degree of abstinence, decriminalization, physical comorbidity and mortality. Finally the cost of treated and untreated drug dependence should be considered.

Dynamic shadow mask technique: a universal tool for nanoscience.

A comprehensive instrument, designed for fabricating nanostructures by evaporation through a dynamic shadow mask in ultrahigh vacuum, is described. The versatility and performance of the instrument is demonstrated through a series of examples, allowing for applications that are impossible to achieve with traditional nanopatterning methods. Clean nanostructures or entire devices made of different materials and on various substrates can be fabricated. The technique is compatible with fundamental surface science and can be easily interfaced with other fabrication and characterization techniques.

[Diagnosis, therapy and follow-up of diabetic eye diseases]. / Diabetische Augenerkrankungen: Diagnose, Therapie und Verlaufskontrolle.

Diabetes mellitus causes diabetic retinopathy and maculopathy, optical nerve neuropathy, cataract and defects of the eye muscles. The incidence of these defects correlates with duration and quality of the metabolic control. The recommendations of the Austrian Diabetes Association for the diagnosis, the therapeutic measures and requirements for adequate follow-up depending on the stages of the different forms of diabetic eye diseases are summarized.