Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients.

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.

Comparative study of 0.1% hyaluronic acid versus 0.5% carboxymethylcellulose in patients with dry eye associated with moderate keratitis or keratoconjunctivitis.

BACKGROUND: Eye drops containing 0.1% hyaluronic acid (HA) and 0.5% carboxymethylcellulose (CMC) applied one drop three times a day per affected eye were compared in patients with moderate keratitis or keratoconjunctivitis related to dry eye disease (DED). PATIENTS AND METHODS: This was a prospective, randomized, multicenter, Phase IIIB noninferiority study, with a single-masked phase in parallel mode with two groups over 84 days. The primary efficacy outcome was change in ocular surface (OS) staining between day 0 (D0) and day 35 (D35). The conjunctiva and cornea were stained with lissamine green and fluorescein. Secondary efficacy measures at day 84 (D84) were OS-staining score (SS), ocular comfort index, tear-film breakup time and how patients and investigators rated treatment efficacy and safety. RESULTS: At D35, 0.1% HA achieved a 46.6% reduction in OS-SS (-2.03±1.35 points, n=39 patients) and 0.5% CMC treatment, followed by a 34.9% reduction (-1.61±1.69 points, n=38 patients) compared to D0. At D84, the SS difference to D0 improved by -2.58±1.45 points (-59.2%) for 0.1% HA and -2.59±2.27 points (-54.4%) for 0.5% CMC. Ocular comfort-index scores improved, with significantly lower (better) values for stinging and itching on D84 for 0.1% HA. Patients assessed treatment with 0.1% HA as significantly better than 0.5% CMC (Likert scale, 4.82 vs 3.97; P=0.018). Four adverse events (AEs) occurred in four of 41 patients (9.8%) treated with 0.1% HA, and three AEs in two of 39 patients (5.1%) treated with 0.5% CMC. No serious AEs were noted. CONCLUSION: DED signs and symptoms of DED significantly improved with both eye drops. OS staining improved >54% at D84. Treatment was well tolerated, with only minor AEs <10%. 0.1% HA and 0.5% CMC were equally safe and effective. Significant and nonsignificant results were constantly in favor of 0.1% HA.

Comparison of 0.2% and 0.18% hyaluronate eye drops in patients with moderate to severe dry eye with keratitis or keratoconjunctivitis.

PURPOSE: Comparison of efficacy and safety of 0.2% and 0.18% hyaluronic acid (HA) eye drops three times a day (tid) in patients with moderate to severe dry eye disease, related to keratitis or keratoconjunctivitis. PATIENTS AND METHODS: Prospective, multicenter, randomized, single-masked, phase IIIb, noninferiority study (0.2% HA vs 0.18% HA) in two parallel groups over a period of 84 days. N=70 patients were evaluated. Primary efficacy outcome was ocular surface (OS) staining change on day 35 (D35), compared to baseline. Fluorescein and lissamine green were used for staining of cornea and conjunctiva. Secondary efficacy outcome included tear film breakup time, OS staining score on day 84 (D84), ocular comfort index, as well as patients' and doctors' evaluation. RESULTS: Compared to day 0 (D0), 0.2% HA achieved a 47.7% reduction in staining score (-3.00±2.81 [standard deviation] points, n=38 patients) at D35; 0.18% HA showed a 41.2% reduction (-2.59±2.20 [standard deviation] points, n=32 patients). Statistical analysis showed noninferiority in efficacy of 0.2% HA compared to 0.18% HA on D35. At D84, the reduction in staining score had further increased to 64.5% for 0.2% HA and to 56.4% for 0.18% HA. Both eye drops improved tear film breakup time and ocular comfort index values. Investigators and patients assessed both treatments with 5 of 7 points (Likert Scale, medians). The rate of adverse events (AE) was 2.3% for 0.2% HA and 7.1% for 0.18% HA with no serious AE. CONCLUSION: 0.2% and 0.18% HA eye drops significantly improved signs and symptoms of dry eye disease and were well tolerated with few AEs. Noninferiority of 0.2% HA compared to 0.18% HA was demonstrated for reduction of OS lesions. In some parameters, there was a nonsignificant trend in favor of 0.2% HA concentration.

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

BACKGROUND: The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects. RESULTS: Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated. CONCLUSION: Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15464650.

Successful treatment of blepharitis with bibrocathol (Posiformin® 2 %).

BACKGROUND: Bibrocathol is a well-established antiseptic drug for the treatment of acute eyelid diseases like blepharitis. Despite its frequent use in clinical practice, no controlled clinical trial on the efficacy of bibrocathol 2% eye ointment has been performed until now. The aim of the study was to investigate efficacy, safety and tolerability of bibrocathol (Posiformin® 2 %) eye ointment in patients diagnosed with blepharitis. METHODS: In this multi-center, randomized, double-masked, placebo-controlled parallel-group comparison, the change of signs and symptoms (sum score) of blepharitis in 197 patients (ITT (intention-to-treat-group); mean age 56 ± 18 years, 56 % female, active drug:vehicle = 97:100) over 2 weeks treatment with bibrocathol 2 % eye ointment was evaluated. RESULTS: Patients receiving bibrocathol 2 % showed greater improvement in the sum score than the placebo patients (p < 0.0001, Cohen's effect size d = 0.73). Also, the results from further efficacy assessments improvement of single symptoms and ocular discomfort measured by a VAS (visual analogue scale) supported treatment with bibrocathol. Patients and investigators provided favorable tolerability ratings preferring bibrocathol over placebo. No safety issues were observed with regard to intraocular pressure, visual acuity, or occurrence of adverse events. CONCLUSIONS: Blepharitis therapy with the antiseptic bibrocathol 2 % in this trial was highly efficacious and safe.

A comparative evaluation of corneal epithelial cell cultures for assessing ocular permeability.

The purpose of this study was to evaluate the potential value of different epithelial cell culture systems as in vitro models for studying corneal permeability. Transformed human corneal epithelial (HCE-T) cells and Statens Serum Institut rabbit corneal (SIRC) cells were cultured on permeable filters. SkinEthic human corneal epithelium (S-HCE) and Clonetics human corneal epithelium (C-HCE) were received as ready-to-use systems. Excised rabbit corneas (ERCs) and human corneas (EHCs) were mounted in Ussing chambers, and used as references. Barrier properties were assessed by measuring transepithelial electrical resistance, and by determining the apparent permeability of markers with different physico-chemical properties, namely, fluorescein, sodium salt; propranolol hydrochloride; moxaverine hydrochloride; timolol hydrogenmaleate; and rhodamine 123. SIRC cells and the S-HCE failed to develop epithelial barrier properties, and hence were unable to distinguish between the permeation markers. Barrier function and the power to differentiate compound permeabilities were evident with HCE-T cells, and were even more pronounced in the case of C-HCE, corresponding very well with data from ERCs and EHCs. A net secretion of rhodamine 123 was not observed with any of the models, suggesting that P-glycoprotein or similar efflux systems have no significant effects on corneal permeability. Currently available corneal epithelial cell culture systems show differences in epithelial barrier function. Systems lacking functional cell-cell contacts are of limited value for assessing corneal permeability, and should be critically evaluated for other purposes.

[Comparative clinical study of two dexamethasone phosphate-containing ophthalmics]. / Klinische Studie zum Nachweis der Vergleichbarkeit von zwei Dexamethasonphosphat-haltigen Ophthalmika.

For the drug application of the already known active ingredient dexamethasone dihydrogen phosphate disodium salt (CAS 2392-39-4) for ocular use clinical data on the efficacy and safety were required by the drug regulatory agency. The comparison of the pharmaceutical properties had already shown that no differences in clinical use had to be expected. The results of a double-blind, randomised, comparative clinical study on 210 patients prove that no differences between test and comparator product could be observed. This case shows that the demand for clinical trials to proof therapeutic equivalence should be done with a sense of proportion related to the specific situation.

[Evidence-based nursing--a comprehensive term]. / Evidence Based Nursing--der umfassende Begriff.

The connotation of Evidence Based Nursing, patient centred care, decisions in health care, intuition and evidence based on international published research is presented. A distinction between Evidence Based Medicine and Evidence Based Nursing in terms of evidence and the hierarchy of evidence is necessary. The concept of Evidence Based Nursing for the last few years has been including practical expertise and patient choice. In nursing the selection of research articles for implementation rely not solely on the evidence hierarchy but also on the model of Rycroft-Malone et al. (2002). The term Evidence Based Patient Choice was the answer to the declaration of patient rights. These rights about accurate and detailed information are essential, so that patients can actively be involved in the decision making process about the management of their disease. Nurses, therefore, must reflect and verbalize the intuition behind the decisions in a systematic and institutionalised way to include in their future decisions for similar cases the full range of evidence.