Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

The Decrease in Mitochondrial DNA Mutation Load Parallels Visual Recovery in a Leber Hereditary Optic Neuropathy Patient.

The onset of Leber hereditary optic neuropathy is relatively rare in childhood and, interestingly, the rate of spontaneous visual recovery is very high in this group of patients. Here, we report a child harboring a rare pathological mitochondrial DNA mutation, present in heteroplasmy, associated with the disease. A patient follow-up showed a rapid recovery of the vision accompanied by a decrease of the percentage of mutated mtDNA. A retrospective study on the age of recovery of all childhood-onset Leber hereditary optic neuropathy patients reported in the literature suggested that this process was probably related with pubertal changes.

[Health and safety professional roles and competencies to promote company-level integration of preventive actions. A Delphy study]. / Roles y competencias de los profesionales de la salud laboral para promover la integración de la prevención en la empresa. Un estudio Delphi.

OBJECTIVE: To describe the view of faculty who train health and safety professionals on the roles and competencies needed to promote the integration of preventive actions at the company level. METHODS: We used a Delphi method, in three rounds, on an intentional sample of experts, and asked them to rate the appropriateness, relevance and acceptability of 8 professional roles, on a scale of 1 to 9 points. We also asked them to formulate and rank order the corresponding competencies, in order of importance. RESULTS: Participant responses (n=76, 58% of the initially identified faculty) show a broad consensus when assessing professional roles (over 85% of participants rated two of these roles highly, with scores between 7 and 9) and general agreement on the three most important competencies in terms of knowledge, skills and attitudes to promote the integration of preventive actions. CONCLUSIONS: The experts participating in this study agreed that the main roles to be performed by health and safety professionals to promote prevention integration are as advisors and trainers. The competencies considered most important are knowledge about the company activity, its risks and the problems linked to the activity (to know), ability to work in multidisciplinary teams (to know how), and to perform professional duties ethically, with independence and impartiality (to know how to be).

OBJETIVO: Conocer el punto de vista de docentes que forman prevencionistas acerca de cuáles son los roles y competencias necesarios en los profesionales de la salud laboral para promover la integración de la prevención en la empresa. MÉTODO: Se utiliza la técnica Delphi en triple vuelta sobre una muestra intencional de expertos a los que se pidió que puntuaran en una escala de 1 a 9 la pertinencia, relevancia y aceptabilidad de un listado de ocho roles, y que enunciaran y ordenaran según su importancia las correspondientes competencias. RESULTADOS: Las respuestas obtenidas de los participantes (n=76, 58% de los docentes en el listado inicial) muestran amplio consenso en la valoración de los roles (más del 85% de los participantes coinciden en otorgar puntuaciones altas ­entre 7 y 9­ para dos de los ocho roles listados) así como un acuerdo generalizado sobre las tres competencias más importantes en relación con los conocimientos, habilidades y actitudes adecuadas para promover la integración de la prevención en la empresa. CONCLUSIONES: En opinión de los expertos participantes los principales roles que debe ejercer el profesional de salud laboral para promover la integración de la prevención son el de asesor y el de formador. Las competencias consideradas como más importantes son el conocimiento de la actividad de la empresa así como los riesgos y los problemas derivados de dicha actividad (saber), la capacidad de trabajar en equipos multidisciplinares (saber hacer), y el poseer ética profesional, independencia e imparcialidad (saber ser, estar).

Agenesis of internal carotid artery in a child with ipsilateral Horner's syndrome.

Horner's syndrome is characterized by a classic triad of ipsilateral pupillary miosis, partial eyelid ptosis, and facial anhydrosis. This case study reports a 7-year-old boy with right miosis, mild blepharoptosis, and iris hypopigmentation detected in a routine pediatric follow-up without ipsilateral facial anhydrosis, flushing, or pain. There was no history of birth trauma and test with cocaine provoked no response of the right pupil, suggesting right Horner's syndrome. Mediastinal tumor was ruled out and brain magnetic resonance imaging incidentally showed absence of flow in the right internal carotid artery. Subsequent magnetic resonance angiography demonstrated agenesis of the right internal carotid artery without other vascular-associated malformations. The final diagnosis was right, congenital Horner's syndrome due to ipsilateral internal carotid agenesis. We describe in detail the radiological findings and pathophysiological mechanisms of this unusual association.