Treatment Complexity in Primary Open-Angle Glaucoma (POAG): Perspectives on Patient Selection in Micro-Invasive Glaucoma Surgery (MIGS) Using Stents. / Versorgungskomplexität beim primären Offenwinkelglaukom (POWG): Perspektiven zur Patientenauswahl in der mikroinvasiven Glaukomchirurgie (MIGS) mit Stents.

BACKGROUND: Primary open-angle glaucoma (POAG) is still one of the most common causes of impaired vision worldwide, despite the further development of therapy options, and can lead to blindness. Micro-invasive glaucoma surgery (MIGS) using stents aims at reducing intraocular pressure (IOP), as it is the main risk factor. With regard to adherence and adverse drug reactions it also aims at reducing the drug burden on patients. The study investigates under everyday conditions the criteria according to which ophthalmologists in Germany select patients for MIGS using stents. In addition, it will be investigated which patients (could) benefit most from the therapy. MATERIAL AND METHODS: In this qualitative study, 11 narrative interviews were conducted between May 2017 and July 2018 with ophthalmologists working in the hospital or in a private practice. They were interviewed on their experiences in the treatment of POAG with microstents. The interviews were analysed by an interdisciplinary team using the qualitative content analysis. RESULTS: The stages of therapy escalation form the frame of reference for patient selection in MIGS using stents. Only if the IOP cannot be sufficiently reduced by drop therapy or when this causes drug-related side effects that are intolerable for the patients, stents are apparently used as the next higher escalation stage. The intensive post-operative medication and the frequent check-up appointments are perceived as barriers by the interviewees, especially for people with or without disabilities, who are dependent on external help and/or those living in rural areas. The active cooperation of the patients in the demanding aftercare seems to be indispensable for the ophthalmologists. In addition, necessary revisions are sometimes stressful for patients (physical/psychological) and doctors (work organisation/therapy). Against the background of the organisational and economic challenges in the outpatient spectrum of tasks, especially physicians in private practice seem to weigh up carefully for which patients microstent therapy would be reasonable. CONCLUSION: In view of the therapeutic requirements, the current microstent therapy seems to be used in a selected, adherent patient group. Further qualitative and quantitative studies (in other health care regions and structures) are necessary to verify and extend the available results.

In-vivo-validation of a cardiovascular risk prediction tool: the arriba-pro study.

BACKGROUND: Calculation of individual risk is the cornerstone of effective cardiovascular prevention. arriba is a software to estimate the individual risk to suffer a cardiovascular event in 10 years. Prognosis and the absolute effects of pharmacological and lifestyle interventions help the patient make a well-informed decision. The risk calculation algorithm currently used in arriba is based on the Framingham risk algorithm calibrated to the German setting. The objective of this study is to evaluate and adapt the algorithm for the target population in primary care in Germany. METHODS/DESIGN: arriba-pro will be conducted within the primary care scheme provided by a large health care insurer in Baden-Württemberg, Germany. Patients who are counseled with arriba by their general practitioners (GPs) will be included in the arriba-pro cohort. Exposure data from the consultation with arriba such as demographic data and risk factors will be recorded automatically by the practice software and transferred to the study centre. Information on relevant prescription drugs (effect modifiers) and cardiovascular events (outcomes) will be derived from administrative sources. DISCUSSION: The study is unique in simulating a therapy naïve cohort, matching exactly research and application setting, using a robust administrative data base, and, finally, including patients with known cardiovascular disease who have been excluded from previous studies. TRIAL REGISTRATION: The study is registered with Deutsches Register Klinischer Studien (DRKS00004633).

Converting habits of antibiotic prescribing for respiratory tract infections in German primary care--the cluster-randomized controlled CHANGE-2 trial.

BACKGROUND: With an average prescription rate of 50%, in German primary care antibiotics are still too frequently prescribed for respiratory tract infections. The over-prescription of antibiotics is often explained by perceived patient pressure and fears of a complicated disease progression. The CHANGE-2 trial will test the effectiveness of two interventions to reduce the rate of inappropriate antibiotic prescriptions for adults and children suffering from respiratory tract infections in German primary care. METHODS/DESIGN: The study is a three-arm cluster-randomized controlled trial that measures antibiotic prescription rates over three successive winter periods and reverts to administrative data of the German statutory health insurance company AOK. More than 30,000 patients in two regions of Germany, who visit their general practitioner or pediatrician for respiratory tract infections will be included. Interventions are: A) communication training for general practitioners and pediatricians and B) intervention A plus point-of-care testing. Both interventions are tested against usual care. Outcome measure is the physicians' antibiotic prescription rate for respiratory tract infections derived from data of the health insurance company AOK. Secondary outcomes include reconsultation rate, complications, and hospital admissions. DISCUSSION: Major aim of the study is to improve the process of decision-making and to ensure that patients who are likely to benefit from antibiotics are treated accordingly. Our approach is simple to implement and might be used rapidly among general practitioners and pediatricians. We expect the results of this trial to have major impact on antibiotic prescription strategies and practices in Germany, both among general practitioners and pediatricians. TRIAL REGISTRATION: The study is registered at the Current Controlled Trials Ltd (ISRCTN01559032).

Patterns and Facilitators for the Promotion of Glaucoma Medication Adherence-A Qualitative Study.

Primary open-angle glaucoma (POAG) is a chronic optic neuropathy causing irreversible nerve fiber damage. Initially asymptomatic, it progresses slowly without any notable sign of vision loss, thus early detection and treatment is essential. The standard treatment being non-invasive topical administration of eye drops harbors the problem of patients not being adherent. This study aimed to explore the experiences and thoughts of glaucoma patients about their medication management to improve our knowledge on how adherence works for the individual patient. Narrative interviews were conducted with 21 glaucoma patients. Data were analyzed using inductive content analysis and the documentary method. Different patterns of adherence were identified which depended on personal biographies, living conditions, or the patient's knowledge about the disease. Interpreting eye drop medication as a ritual, a task, or routine was helpful for some patients, whereas other patients, who were aware of the consequences of not taking the drops, were motivated by intrinsic or extrinsic factors. The patterns identified here represent strategies for managing and adhering to daily glaucoma medication at an individual level. Linking daily drop application or medication intake to these patterns may help to promote correct medication management of patients with chronic diseases who lack a regular medication regimen.

Inhibitory effects of phthalimide derivatives on the activity of the hepatic cytochrome P450 monooxygenases CYP2C9 and CYP2C19.

Affecting hepatic cytochrome (CYP) activity is one of the major concerns in drug-drug interaction. Thus the testing of drug candidates on their impact on these enzymes is an essential step in early drug discovery. We tested a collection of 480 in-house phthalimide derivatives against different CYP450s using a high throughput inhibition assay. In initial tests with the isoform CYP2C19 about 57.5% of the tested phthalimide derivatives showed significantly enhanced inhibitory effects against this enzyme. In addition similar patterns of phthalimide inhibition for CYP2C9 and CYP2C19 were found, whereas the unrelated isoforms CYP2D6 and CYP3A4 were not specifically affected. Also less than 10% of randomly chosen substances inhibited CYP2C9. Analyses of structure-function relationships revealed that the substituent at the nitrogen atom in the isoindole ring is of crucial impact for the activity of CYP2C9/19.

Hospitalization for Acute Respiratory Tract Infection in a Low-Antibiotic-Prescribing Setting: Cross-Sectional Data from General Practice.

BACKGROUND: Acute respiratory tract infections (ARTI) are the main cause of inappropriate antibiotic prescribing. To date, there is limited evidence concerning whether low levels of antibiotic prescribing may impact patient safety. We investigate whether antibiotic prescribing for patients seeking primary care for ARTI correlates with the odds for hospitalization. METHODS: Analysis of patient baseline data (n = 3669) within a cluster-randomized controlled trial. Adult patients suffering from ARTI in German primary care are included. The main outcome measure is acute hospitalization for respiratory infection and for any acute disease from 0 to 42 days after initial consultation. RESULTS: Neither the antibiotic status of individual patients (OR 0.91; 95% CI: 0.49 to 1.69; p-value = 0.769) nor the physician-specific antibiotic prescription rates for ARTI (OR 1.22; 95% CI: 1.00 to 1.49; p-value = 0.054) had a significant effect on hospitalization. The following factors increased the odds for hospitalization: patient's age, the ARTI being defined as lower respiratory tract infections (such as bronchitis) by the physician, the physician's perception of disease severity, and being cared for within group practices (versus treated in single-handed practices). CONCLUSIONS: In a low-antibiotic-prescribing primary care setting such as Germany, lack of treatment with antibiotics for ARTI did not result in higher odds for hospitalization in an adult population.

Control of focal adhesion dynamics by material surface characteristics.

The mechanisms of cell adhesion to the extracellular matrix (ECM) which are of fundamental importance for function, survival, and growth of cells involve the formation of focal adhesions to facilitate integrin signaling. Recently, it became evident that focal adhesions are not stable but move to enable cell migration and ECM formation. We examined the number, size, and dynamic behavior of focal adhesions in living MG-63 osteoblastic cells, which were cultured on titanium surfaces with different roughnesses and on stainless steel (SS). As a marker for focal adhesions we used GFP-tagged vinculin, a cytoskeletal protein. Focal adhesions were smaller on titanium and on SS than on collagen-coated glass coverslips. The corundum-blasted rough surface of titanium induced the smallest adhesions. On all the surfaces that we have tested, we observed a mobility of focal adhesions. On collagen-coated coverslips focal adhesions moved with a speed of 60 nm/min. The speed was reduced on titanium and still more restricted on SS. The topography did not affect the mobility of focal adhesions. We conclude that on the material surfaces that we have studied a reduced mobility of focal adhesions may strengthen the linkages between cell and ECM but impair the ability to dynamically organize and remodel the ECM. The results may have a great impact in the functional evaluation of tailored biomaterial surfaces for the application in tissue engineering.

Calcium phosphate surfaces promote osteogenic differentiation of mesenchymal stem cells.

Although studies in vivo revealed promising results in bone regeneration after implantation of scaffolds together with osteogenic progenitor cells, basic questions remain how material surfaces control the biology of mesenchymal stem cells (MSC). We used human MSC derived from bone marrow and studied the osteogenic differentiation on calcium phosphate surfaces. In osteogenic differentiation medium MSC differentiated to osteoblasts on hydroxyapatite and BONITmatrix, a degradable xerogel composite, within 14 days. Cells revealed a higher alkaline phosphatase (ALP) activity and increased RNA expression of collagen I and osteocalcin using real-time RTPCR compared with cells on tissue culture plastic. To test whether material surface characteristics alone are able to stimulate osteogenic differentiation, MSC were cultured on the materials in expansion medium without soluble additives for osteogenic differentiation. Indeed, cells on calcium phosphate without osteogenic differentiation additives developed to osteoblasts as shown by increased ALP activity and expression of osteogenic genes, which was not the case on tissue culture plastic. Because we reasoned that the stimulating effect on osteogenesis by calcium phosphate surfaces depends on an altered cell-extracellular matrix interaction we studied the dynamic behaviour of focal adhesions using cells transfected with GFP labelled vinculin. On BONITmatrix, an increased mobility of focal adhesions was observed compared with cells on tissue culture plastic. In conclusion, calcium phosphate surfaces are able to drive MSC to osteoblasts in the absence of osteogenic differentiation supplements in the medium. An altered dynamic behaviour of focal adhesions on calcium phosphate surfaces might be involved in the molecular mechanisms which promote osteogenic differentiation.