Impact of a comprehensive prevention programme aimed at reducing incivility and verbal violence against healthcare workers in a French ophthalmic emergency department: an interrupted time-series study.

Primary prevention, comprising patient-oriented and environmental interventions, is considered to be one of the best ways to reduce violence in the emergency department (ED). We assessed the impact of a comprehensive prevention programme aimed at preventing incivility and verbal violence against healthcare professionals working in the ophthalmology ED (OED) of a university hospital. The programme was designed to address long waiting times and lack of information. It combined a computerised triage algorithm linked to a waiting room patient call system, signage to assist patients to navigate in the OED, educational messages broadcast in the waiting room, presence of a mediator and video surveillance. All patients admitted to the OED and those accompanying them. Single-centre prospective interrupted time-series study conducted over 18 months. Violent acts self-reported by healthcare workers committed by patients or those accompanying them against healthcare workers. Waiting time and length of stay. There were a total of 22 107 admissions, including 272 (1.4%) with at least one act of violence reported by the healthcare workers. Almost all acts of violence were incivility or verbal harassment. The rate of violence significantly decreased from the pre-intervention to the intervention period (24.8, 95% CI 20.0 to 29.5, to 9.5, 95% CI 8.0 to 10.9, acts per 1000 admissions, p<0.001). An immediate 53% decrease in the violence rate (incidence rate ratio=0.47, 95% CI 0.27 to 0.82, p=0.0121) was observed in the first month of the intervention period, after implementation of the triage algorithm. A comprehensive prevention programme targeting patients and environment can reduce self-reported incivility and verbal violence against healthcare workers in an OED. NCT02015884

Efficacy and safety of glycyrrhizin 2.5% eye drops in the treatment of moderate dry eye disease: results from a prospective, open-label pilot study

Carole Burillon,1 Frederic Chiambaretta,2 Pierre-Jean Pisella3 1Ophthalmology Department, University Hospital HCL, GH Edouard Herriot, Lyon, France; 2Ophthalmology Department, Clermont-Ferrand University Hospital, Hôpital Gabriel Montpied, Clermont Ferrand, France; 3Ophthalmology Department, Paris Nord Val-de-Seine University Hospitals, Hôpital Bretonneau, Tours, France Background: Dry eye disease (DED) is characterized by a loss of homeostasis of the tear film. It goes along with ocular symptoms, in which ocular surface inflammation and damage play etiological roles. High-mobility group box 1 protein (HMGB1) is a pro-inflammatory protein found in the tear fluid during conjunctivitis, blepharitis and DED. Glycyrrhizin binds to HMGB1, inhibiting cytokine activities, thus potentially improving DED.Aim: To assess the efficacy and tolerance of glycyrrhizin in moderate DED.Methods: Multicenter, open-label, prospective, nonrandomized clinical pilot study of glycyrrhizin 2.5% eye drops twice daily over 28 days in adult patients with moderate DED using standard evaluation parameters.Results: The overall mean age of the 37 patients included was 59.6±19.0 years, 70.3% of the patients were female and 77.0% of the patients had an Oxford score of II. After 28 days, 60.8% of the patients had an Oxford score of 0 or I; a significant mean improvement in the score of 0.97±0.86 (P<0.001) from 2.20±0.44 at day 1 to 1.23±0.88 at day 28 was observed. Tear break-up time and Schirmer scores had significantly improved while the number of patient-reported symptoms had significantly decreased (all P≤0.010). A large majority of patients still had a few spots on their naso-bulbar conjunctiva (86.1%), temporal-bulbar conjunctiva (81.4%) and cornea (84.7%). The investigators considered that DED had improved in 71.6% of the patients. Patients appreciated the eye drops for their efficacy and good tolerance profile, leading to a decreased use of artificial tears. No changes in intraocular pressure and visual acuity were observed; glycyrrhizin 2.5% eye drops were safe, with only one patient reporting a moderate, transient treatment-related contact allergy leading to the withdrawal of the patient. Overall, two patients reported three adverse events, two (moderate contact allergy in both eyes) were related to the eye drops and experienced by the same patient; treatment was stopped; the third event was not treatment-related.Conclusion: In this pilot study, glycyrrhizin 2.5% eye drops were well tolerated and provide a good clinical benefit to patients with moderate DED after 28 days of continued daily use. Keywords: dry eye disease, hyaluronic sodium, glycyrrhizin, inflammation, ocular lesion

Human corneal fibrillogenesis. Collagen V structural analysis and fibrillar assembly by stromal fibroblasts in culture.

International audiencePURPOSE. The stroma of the developing cornea is a highly organized extracellular matrix formed essentially by uniform, small-diameter collagen fibrils with constant interfibrillar spacing. Unlike the fibrillogenesis of chicken cornea, the assembly and maturation of human corneal fibrils have been poorly investigated. In the current study, the authors aimed to ascertain the heterotypic organization (collagens I and V) of the human corneal fibrils at the supramolecular level. To gain more insight into the molecular structure of collagen V, its cellular source, and its role in fibrillogenesis, the authors used cultured human corneal fibroblasts. METHODS. The structure of human corneal stroma after brief homogenization of the tissue was analyzed by immunogold labeling using specific polyclonal antibodies and rotary shadowing. Biochemical, electron microscopic, and immunolabeling approaches were used to investigate the collagen fibril formation and the extracellular matrix synthesis using human corneal fibroblasts grown in culture as a model system. RESULTS. The authors showed that in human corneal stroma, collagen I is distributed uniformly along the striated fibrils, in contrast to collagen V, which could be identified only at sites at which the fibrils partially were disrupted. Rotary shadowing observations of the homogenate revealed that collagen VI, a major component of the human cornea, was associated closely with the collagen fibril surface. Corneal fibroblasts synthesize and deposit a collagenous matrix with fibrils resembling those of the human cornea in appearance and collagen composition. Biochemical data indicate that a high concentration (20% to 30%) of collagen V is synthesized by stromal fibroblasts and that collagen V molecules are processed similarly to matrix forms in which the extension peptides are retained on the molecules. CONCLUSIONS. The heterotypic nature (collagens I and V) of human corneal fibrils was determined. Results indicate that human corneal fibroblasts synthesize the major collagen types in human cornea (collagens I, V, and VI) and express all the posttranslational equipment for correct collagen molecular assembly and processing in a manner that closely resembles the situation in situ, offering the opportunity for more detailed study of this process, which is essential for optical transparency.PURPOSE. The stroma of the developing cornea is a highly organized extracellular matrix formed essentially by uniform, small-diameter collagen fibrils with constant interfibrillar spacing. Unlike the fibrillogenesis of chicken cornea, the assembly and maturation of human corneal fibrils have been poorly investigated. In the current study, the authors aimed to ascertain the heterotypic organization (collagens I and V) of the human corneal fibrils at the supramolecular level. To gain more insight into the molecular structure of collagen V, its cellular source, and its role in fibrillogenesis, the authors used cultured human corneal fibroblasts. METHODS. The structure of human corneal stroma after brief homogenization of the tissue was analyzed by immunogold labeling using specific polyclonal antibodies and rotary shadowing. Biochemical, electron microscopic, and immunolabeling approaches were used to investigate the collagen fibril formation and the extracellular matrix synthesis using human corneal fibroblasts grown in culture as a model system. RESULTS. The authors showed that in human corneal stroma, collagen I is distributed uniformly along the striated fibrils, in contrast to collagen V, which could be identified only at sites at which the fibrils partially were disrupted. Rotary shadowing observations of the homogenate revealed that collagen VI, a major component of the human cornea, was associated closely with the collagen fibril surface. Corneal fibroblasts synthesize and deposit a collagenous matrix with fibrils resembling those of the human cornea in appearance and collagen composition. Biochemical data indicate that a high concentration (20% to 30%) of collagen V is synthesized by stromal fibroblasts and that collagen V molecules are processed similarly to matrix forms in which the extension peptides are retained on the molecules. CONCLUSIONS. The heterotypic nature (collagens I and V) of human corneal fibrils was determined. Results indicate that human corneal fibroblasts synthesize the major collagen types in human cornea (collagens I, V, and VI) and express all the posttranslational equipment for correct collagen molecular assembly and processing in a manner that closely resembles the situation in situ, offering the opportunity for more detailed study of this process, which is essential for optical transparency

ULTRASTRUCTURAL CHARACTERISTICS OF HUMAN STROMA COLLAGEN-FIBERS AND THE ROLES OF THE VARIOUS COLLAGEN ISOTYPES FOUND

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RECONSTRUCTION OF A FULL-THICKNESS COLLAGEN-BASED HUMAN ORAL MUCOSAL EQUIVALENT

Tissue engineered human oral mucosa has the potential to be applied to the closure of surgical wounds after tissue deficits due to facial trauma, malignant lesion surgery or preposthetic procedure. It can also be used to elucidate the biology and pathology of oral mucosa and as a model alternative to animals for safety testing of oral care products. Using the technology previously developed in our laboratory for the production of a skin equivalent, we were able to reconstruct a nonkeratinized full-thickness human oral mucosal equivalent closely mimicking human native oral mucosa. The successive coculture of human lamina propria fibroblasts and human oral epithelial cells isolated from the nonkeratinized region of oral cavity in a porous collagen–glycosaminoglycan (GAG)–chitosan scaffold gave rise to a lamina propria equivalent (LPE) and then to an oral mucosa equivalent (OME). The results of the histology, immunohistology and transmission electron microscopy of this OME demonstrated the presence of a nonkeratinized pluristratified and differentiated epithelium as in native nonkeratinized human oral mucosa expressing both K13 and K3/76. This epithelium was firmly anchored to the LPE by a continuous and ultrastructurally well-organized basement membrane. In the LPE, fibroblasts synthesized new extracellular matrix where the average collagen fibre diameter was 28.4 nm, close to that of native oral mucosa. The proliferative capacity of the basal cells was demonstrated by the expression of Ki6