Measurement proprieties of the CROM instrument for assessing head posture, neck retraction and protraction.

BACKGROUND: The CROM instrument is widely used clinically and in research to measure neck range of motion. However, its measurement proprieties during the assessment of protraction and retraction movements were not examined so far. OBJECTIVE: To analyse the intra- and inter-rater reliability, the concurrent validity of the CROM for measuring head posture, retraction and protraction in healthy subjects. METHODS: Thirty-three asymptomatic subjects were recruited and assigned in a random order to one of two raters. After a 10-min break, they were examined by a second rater (Assessment 1). After a 30-min break, both raters repeated the examination (Assessment 2). The examination consisted of measuring the head posture, maximum head protraction and maximum retraction. Each movement was repeated 3 times and measured simultaneously with the CROM and with a 3D capture system laboratory. RESULTS: The intra-rater reliability of the CROM was excellent for both raters for head posture and all head movements (ICC>0.9, 95% CI: 0.82-0.99, p < 0.01). The inter-rater reliability was excellent for head posture (ICC>0.95, 95% CI: 0.92-0.98, p < 0.01) and good-to-excellent for all movements at both time-points (ICC = 0.73-0.98, 95%CI: 0.45-0.99, p < 0.01). The validity analysis showed moderate-to-strong correlation between instruments for the head posture and head movements [(r) = -0.47 to -0.78), 95% CI: 0.99 to -0.24, p < 0.01]. CONCLUSION: The CROM instrument has good-to-excellent reliability and adequate validity for measuring cervical position and displacement in the sagittal plane.

Multidisciplinary Consensus on the Management of Non-Invasive Respiratory Support in the COVID-19 Patient.

Acute respiratory failure due to COVID-19 pneumonia often requires a comprehensive approach that includes non-pharmacological strategies such as non-invasive support (including positive pressure modes, high flow therapy or awake proning) in addition to oxygen therapy, with the primary goal of avoiding endotracheal intubation. Clinical issues such as determining the optimal time to initiate non-invasive support, choosing the most appropriate modality (based not only on the acute clinical picture but also on comorbidities), establishing criteria for recognition of treatment failure and strategies to follow in this setting (including palliative care), or implementing de-escalation procedures when improvement occurs are of paramount importance in the ongoing management of severe COVID-19 cases. Organizational issues, such as the most appropriate setting for management and monitoring of the severe COVID-19 patient or protective measures to prevent virus spread to healthcare workers in the presence of aerosol-generating procedures, should also be considered. While many early clinical guidelines during the pandemic were based on previous experience with acute respiratory distress syndrome, the landscape has evolved since then. Today, we have a wealth of high-quality studies that support evidence-based recommendations to address these complex issues. This document, the result of a collaborative effort between four leading scientific societies (SEDAR, SEMES, SEMICYUC, SEPAR), draws on the experience of 25 experts in the field to synthesize knowledge to address pertinent clinical questions and refine the approach to patient care in the face of the challenges posed by severe COVID-19 infection.

A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle.

The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe an in silico model, which we call the 'Hernandez-Hernandez model', of electrical and Ca2+ signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca2+ signaling during the development of myogenic tone in arterial blood vessels. Although experimental data suggest that KV1.5 channel currents have similar amplitudes, kinetics, and voltage dependencies in male and female myocytes, simulations suggest that the KV1.5 current is the dominant current regulating membrane potential in male myocytes. In female cells, which have larger KV2.1 channel expression and longer time constants for activation than male myocytes, predictions from simulated female myocytes suggest that KV2.1 plays a primary role in the control of membrane potential. Over the physiological range of membrane potentials, the gating of a small number of voltage-gated K+ channels and L-type Ca2+ channels are predicted to drive sex-specific differences in intracellular Ca2+ and excitability. We also show that in an idealized computational model of a vessel, female arterial smooth muscle exhibits heightened sensitivity to commonly used Ca2+ channel blockers compared to male. In summary, we present a new model framework to investigate the potential sex-specific impact of antihypertensive drugs.

High blood pressure is a major risk factor for heart disease, which is one of the leading causes of death worldwide. While drugs are available to control blood pressure, male and female patients can respond differently to treatment. However, the biological mechanisms behind this sex difference are not fully understood. Blood pressure is controlled by cells lining the artery walls called smooth muscle cells which alter the width of blood vessels. On the surface of smooth muscle cells are potassium and calcium channels which control the cell's electrical activity. When calcium ions enter the cell via calcium channels, this generates an electrical signal that causes the smooth muscle to contract and narrow the blood vessel. Potassium ions then flood out of the cell via potassium channels to dampen the rise in electrical activity, causing the muscle to relax and widen the artery. There are various sub-types of potassium and calcium channels in smooth muscle cells. Here, Hernandez-Hernandez et al. set out to find how these channels differ between male and female mice, and whether these sex differences could alter the response to blood pressure medication. The team developed a computational model of a smooth muscle cell, incorporating data from laboratory experiments measuring differences in cells isolated from the arteries of male and female mice. The model predicted that the sub-types of potassium and calcium channels in smooth muscle cells varied between males and females, and how the channels impacted electrical activity also differed. For instance, the potassium channel Kv2.1 was found to have a greater role in controlling electrical activity in female mice, and this sex difference impacted blood vessel contraction. The model also predicted that female mice were more sensitive than males to calcium channel blockers, a drug commonly prescribed to treat high blood pressure. The findings by Hernandez-Hernandez et al. provide new insights into the biological mechanisms underlying sex differences in response to blood pressure medication. They also demonstrate how computational models can be used to predict the effects of drugs on different individuals. In the future, these predictions may help researchers to identify better, more personalized treatments for blood pressure.

COVID-19 pandemic and its impact on medical interns' mental health of public and private hospitals in Guadalajara.

INTRODUCTION: Burnout syndrome is a global burden characterized by exhaustion, work detachment, and a sense of ineffectiveness. It affects millions of individuals worldwide, with a particularly high prevalence among medical students. Factors such as demanding education, exposure to suffering, and the COVID-19 pandemic have contributed to elevated stress levels. Addressing this issue is crucial due to its impact on well-being and health-care quality. MATERIALS AND METHODS: This cross-sectional survey study assessed fear of COVID-19 and burnout levels among medical student interns in hospitals in Guadalajara, Jalisco. The study used validated scales and collected data from September 2021 to September 2022. A snowball sampling method was employed and a minimum sample size of 198 participants was calculated. RESULTS: This study included 311 medical students (62.1% female and 37.9% male with a mean age of 23.51 ± 2.21 years). The majority were in their second semester of internship (60.5%) and from public hospitals (89.1%). Most students believed that the COVID-19 pandemic affected the quality of their internship (82.6%). Female students had higher personal burnout scores, while male students had higher work-related burnout scores. The mean score for fear of COVID-19 was 13.71 ± 6.28, with higher scores among women (p = 0.004) and those from public hospitals (p = 0.009). A positive weak correlation was found between COVID-19 scores and burnout subscales. CONCLUSION: Our study emphasizes the significant impact of various factors on burnout levels among medical students and health-care professionals during the COVID-19 pandemic. Prolonged exposure to COVID-19 patients, reduced staffing, and increased workload contributed to burnout, affecting well-being and quality of care. Targeted interventions and resilience-building strategies are needed to mitigate burnout and promote well-being in health-care settings.

Gingival hypersensitivity reactions to toothpastes: A case series and scoping review.

BACKGROUND: Hypersensitivity reactions to toothpastes are rare. The objective of this study was to present the authors' clinical cases in the past 10 years and perform a scoping review of gingival hypersensitivity responses to toothpastes. TYPES OF STUDIES REVIEWED: The authors reviewed records of documented gingival hypersensitivity reactions to dentifrices at the Postgraduate Clinic of Oral Medicine, Complutense University, Madrid, Spain, from January 2013 through December 2022. Furthermore, the authors conducted a search in PubMed with no date limit for articles reporting these hypersensitivity responses up through October 18, 2023. RESULTS: Eleven cases were collected from the clinic. Eight gingival hypersensitivity reactions occurred in women, and 6 were associated with cinnamon. The most frequent lesions diagnosed were red gingiva. The discontinuation of the toothpaste led to the disappearance of the lesions. The search yielded 643 references. Thirteen articles were included in the scoping review, all of them case series and case reports, reporting 32 cases. Lesions affected middle-aged women most frequently, the most common hypersensitivity reaction was gingival redness, and the cases implicated toothpastes containing cinnamon and herbal composition. PRACTICAL IMPLICATIONS: This study provides clues for diagnosing and treating hypersensitivity reactions to toothpastes, which may improve the identification, management, and reporting of these cases.

A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle.

The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe an in-silico model, which we call the "Hernandez-Hernandez model", of electrical and Ca2+ signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca2+ signaling during the development of myogenic tone in arterial blood vessels. Although experimental data suggest that KV1.5 channel currents have similar amplitudes, kinetics, and voltage dependencies in male and female myocytes, simulations suggest that the KV1.5 current is the dominant current regulating membrane potential in male myocytes. In female cells, which have larger KV2.1 channel expression and longer time constants for activation than male myocytes, predictions from simulated female myocytes suggest that KV2.1 plays a primary role in the control of membrane potential. Over the physiological range of membrane potentials, the gating of a small number of voltage-gated K+ channels and L-type Ca2+ channels are predicted to drive sex-specific differences in intracellular Ca2+ and excitability. We also show that in an idealized computational model of a vessel, female arterial smooth muscle exhibits heightened sensitivity to commonly used Ca2+ channel blockers compared to male. In summary, we present a new model framework to investigate the potential sex-specific impact of anti-hypertensive drugs.

The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial.

PURPOSE: Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). MATERIALS AND METHODS: Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90). RESULTS: Eighty-three patients were randomized and received infusions (Cx611: n = 42]; placebo: n = 41]. The mean age was similar (Cx611: 61.1 [11.2] years; placebo: 63.4 [10.4] years). The number of AEs and treatment-emergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611: n = 9; placebo: n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611: 86.7%; placebo: 93.8%), mean number of ventilator-free days (Cx611: 12.2 [10.29] days; placebo: 15.4 [10.75] days), and overall survival (Cx611: 71.5%; placebo: 77.0%) did not differ between study arms. CONCLUSION: Cx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation. TRIAL REGISTRATION: NCT03158727 (retrospectively registered: May 09, 2017). Full study protocol: https://clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf.

Factors influencing xerostomia and oral health-related quality of life in polymedicated patients.

OBJECTIVES: To evaluate whether the severity of xerostomia in older polymedicated patients impacts oral health-related quality of life (OHRQoL). BACKGROUND: Medication-associated xerostomia is common in older people. Xerostomia may impair OHRQoL. MATERIALS AND METHODS: This cross-sectional study included older hypertensive patients from two health centres. We assessed the severity of xerostomia and OHRQoL using the Xerostomia Inventory (XI) tool, and the Oral Health Impact Profile-14 (OHIP-14) instrument, respectively. We measured unstimulated (UWS) and stimulated (SWS) salivary flows. Univariate and multiple linear regression analyses evaluated the associations of XI and OHIP-14 and different explanatory variables. RESULTS: Of the 218 patients enrolled, 51.8% had xerostomia, and 38.1% and 27.5% suffered from UWS and SWS hyposalivation, respectively. Patients with xerostomia, UWS, and SWS hyposalivation scored significantly higher on the XI. However, only those with xerostomia or UWS hyposalivation had significantly higher OHIP-14 scores. A moderate correlation was observed between XI and OHIP-14 scores. The multiple regression model showed that factors with the greatest impact on XI were the patient's complaint of xerostomia, UWS flow rate, age and sex. However, only the XI score was significantly associated with the OHIP-14 score. CONCLUSION: Xerostomia has a negative impact on OHRQoL in older polymedicated patients, but this impact is less than in other types of xerostomia. Longitudinal studies are needed to determine whether changes in the detected explanatory variables influence XI and OHIP scores in these patients.

The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes.

In arterial myocytes, the canonical function of voltage-gated CaV1.2 and KV2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, KV2.1 also plays a sex-specific role by promoting the clustering and activity of CaV1.2 channels. However, the impact of KV2.1 protein organization on CaV1.2 function remains poorly understood. We discovered that KV2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of KV2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the KV2.1 clustering site (KV2.1S590A) eliminated KV2.1 macro-clustering and sex-specific differences in CaV1.2 cluster size and activity. We propose that the degree of KV2.1 clustering tunes CaV1.2 channel function in a sex-specific manner in arterial myocytes.

Ayahuasca, Personality and Acute Psychological Effects in Neo-Shamanic and Religious Settings in Uruguay.

This study is an interdisciplinary research into Uruguayan ayahuasca users belonging to one neo-shamanic and one Santo Daime group. The study involved the chemical analysis of ayahuasca samples, an ethnographic description of the two traditions and rituals, and the application of psychometric scales to measure personality differences, and the acute psychological effects during an ayahuasca ritual. Personality measurements showed lower scores for Santo Daime in Neuroticism-Anxiety, Dependence, Low Self-Esteem, Anger and Restlessness. These differences may be related to the presence of participants under treatment in the neo-shamanic group and/or to the protective effects of a church religion such as Santo Daime. Regarding acute effects, the neo-shamanic group showed higher scores in Somesthesia and Perception, which can be related to the high-arousal ritual setting. Chemical analysis for the ayahuasca samples showed a typical composition of alkaloids. No adulterants were found. The sample from the neo-shamanic group displayed a higher ß-carbolines:DMT ratio compared to the Santo Daime sample, which could be related to the higher effects observed for Somesthesia for the neo-shamanic group. Significant positive correlations between some personality traits and acute effects were found only in the neo-shamanic group, which may be related to the more individualistic approach of this tradition.

Diagnostic Efficacy of Chest Computed Tomography with a Dual-Reviewer Approach in Patients Diagnosed with Pneumonia Secondary to Severe Acute Respiratory Syndrome Coronavirus 2.

To compare the diagnostic effectiveness of chest computed tomography (CT) utilizing a single- versus a dual-reviewer approach in patients with pneumonia secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted a retrospective observational study of data from a cross-section of 4809 patients with probable SARS-CoV-2 from March to November 2020. All patients had a CT radiological report and reverse-transcription polymerase chain reaction (PCR) results. A dual-reviewer approach was applied to two groups while conducting a comparative examination of the data. Reviewer 1 reported 108 patients negative and 374 patients positive for coronavirus disease 2019 (COVID-19) in group A, and 266 negative and 142 positive in group B. Reviewer 2 reported 150 patients negative and 332 patients positive for COVID-19 in group A, and 277 negative and 131 positive in group B. The consensus result reported 87 patients negative and 395 positive for COVID-19 in group A and 274 negative and 134 positive in group B. These findings suggest that a dual-reviewer approach improves chest CT diagnosis compared to a conventional single-reviewer approach.

The formation of K V 2.1 macro-clusters is required for sex-specific differences in L-type Ca V 1.2 clustering and function in arterial myocytes.

In arterial myocytes, the canonical function of voltage-gated Ca V 1.2 and K V 2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, K V 2.1 also plays a sex-specific role by promoting the clustering and activity of Ca V 1.2 channels. However, the impact of K V 2.1 protein organization on Ca V 1.2 function remains poorly understood. We discovered that K V 2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of K V 2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the K V 2.1 clustering site (K V 2.1 S590A ) eliminated K V 2.1 macro-clustering and sex-specific differences in Ca V 1.2 cluster size and activity. We propose that the degree of K V 2.1 clustering tunes Ca V 1.2 channel function in a sex-specific manner in arterial myocytes.

The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes.

In arterial myocytes, the canonical function of voltage-gated CaV1.2 and KV2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, KV2.1 also plays a sex-specific role by promoting the clustering and activity of CaV1.2 channels. However, the impact of KV2.1 protein organization on CaV1.2 function remains poorly understood. We discovered that KV2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of KV2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the KV2.1 clustering site (KV2.1S590A) eliminated KV2.1 macro-clustering and sex-specific differences in CaV1.2 cluster size and activity. We propose that the degree of KV2.1 clustering tunes CaV1.2 channel function in a sex-specific manner in arterial myocytes.

New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II.

Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.

Consideraciones didácticas acerca de la modalidad no presencial en las universidades / Didactic Considerations about the Non-Face-to-Face Modality in Universities

Introducción: La modalidad no presencial del proceso de enseñanza-aprendizaje se incrementó como respuesta a las condiciones creadas por la COVID-19, sin la necesaria preparación y experiencia de los docentes para implementarla. Objetivo: Proponer algunas consideraciones didácticas que tributan al adecuado manejo del docente de los componentes del proceso de enseñanza-aprendizaje en la implementación de la modalidad no presencial. Posicionamiento de los autores: La exitosa implementación de cualquier variante de modalidad no presencial dependerá de la preparación del docente, particularmente en Didáctica, al asumir las tecnologías de la información y las comunicaciones como medios de enseñanza en la misión de hacer que sus estudiantes aprendan. Conclusiones: La no presencialidad en el proceso de enseñanza-aprendizaje se considera una alternativa viable en circunstancias de pandemia u otras equivalentes, y debe ser una modalidad complementaria en la etapa posCOVID-19. Así que los profesores tendrán que replantear el proceso en todos sus componentes, en un contexto digital que ya no tiene vuelta atrás(AU)

Introduction: Within the teaching-learning process, the non-face-to-face modality was increased as a response to the conditions created by COVID-19, but without the necessary preparation and experience for professors to implement it. Objective: To propose some didactic considerations that contribute to the professor's adequate management of the components of the teaching-learning process in the implementation of the non-face-to-face modality. Authors' position: The successful implementation of any variant of the non-face-to-face modality will depend on the professor's preparation, particularly in didactics, when assuming information and communication technologies as teaching means in the mission of making their students learn. Conclusions: Within the teaching-learning process, the non-face-to-face condition is considered a viable alternative in pandemic, or other equivalent, circumstances; it should be a complementary modality in the post-COVID-19 stage. Thus, professors will have to rethink the process focusing on all its components, within a digital context that has no turning back(AU)

Reactivity of the Iboga Skeleton: Oxidation Study of Ibogaine and Voacangine.

The iboga alkaloids scaffold shows great potential as a pharmacophore in drug candidates for the treatment of neuropsychiatric disorders. Thus, the study of the reactivity of this type of motif is particularly useful for the generation of new analogs suitable for medicinal chemistry goals. In this article, we analyzed the oxidation pattern of ibogaine and voacangine using dioxygen, peroxo compounds, and iodine as oxidizing agents. Special focus was placed on the study of the regio- and stereochemistry of the oxidation processes according to the oxidative agent and starting material. We found that the C16-carboxymethyl ester present in voacangine stabilizes the whole molecule toward oxidation in comparison to ibogaine, especially in the indole ring, where 7-hydroxy- or 7-peroxy-indolenines can be obtained as oxidation products. Nevertheless, the ester moiety enhances the reactivity of the isoquinuclidinic nitrogen to afford C3-oxidized products through a regioselective iminium formation. This differential reactivity between ibogaine and voacangine was rationalized using computational DFT calculations. In addition, using qualitative and quantitative NMR experiments combined with theoretical calculations, the absolute stereochemistry at C7 in the 7-hydroxyindolenine of voacangine was revised to be S, which corrects previous reports proposing an R configuration.

Safety and Tolerability of Bilastine 0.6% Ophthalmic Solution: An 8-Weeks Phase III Study.

Purpose: The objective of this study was to assess the safety and tolerability of preservative-free bilastine 0.6% ophthalmic solution after 8 weeks of once-daily administration in patients with allergic conjunctivitis (AC). Patients and Methods: Multi-center, international, randomized, double blind, placebo-controlled, parallel-group, phase III study of adult patients with seasonal or perennial AC. The study was conducted in 26 centers of 5 European countries. Duration of daily treatment with bilastine 0.6% ophthalmic solution or placebo was 8 weeks. Safety was evaluated by analyzing incidence of ocular treatment-emergent adverse events (TEAEs); additionally, and as secondary parameters, ocular tolerability was assessed, in addition efficacy was also assessed by the average daily total eye symptoms score (TESS). Results: A total of 333 randomized patients with AC were included (bilastine, N=218; placebo, N=115). Mean (SD) age of the patients was 39.9 (13.7) and were 63.7% female. Overall, the percentage of ocular related TEAEs was low, and the percentage of patients with ocular related TEAEs was lower in the bilastine ophthalmic solution group (2.8%) than in the placebo group (4.3%). No severe TEAEs were reported. The ocular symptoms and TESS improved during the trial in both treatment groups. Statistically significant treatment differences were observed at Week 8 for the TESS and all individual ocular symptoms, being significantly better in the bilastine ophthalmic solution group than in placebo group. Conclusion: Bilastine 0.6% ophthalmic solution revealed no safety concerns in patients with AC after 8 weeks of once-daily administration. Bilastine was effective in reducing ocular symptoms associated with AC in response to both seasonal and perennial allergens.