Most biopharmaceutical therapeutics elicit some level of antibody response against the product. This antibody response can, in some cases, lead to potentially serious side effects and/or loss of ...efficacy. Therefore, the immunogenicity of therapeutic proteins is a concern for clinicians, manufacturers and regulatory agencies. In order to assess immunogenicity of these molecules, appropriate detection, quantitation and characterization of antibody responses are necessary. Inadequately designed antibody assays have led to the hampering of product development or, during licensure, post-marketing commitments. This document provides scientific recommendations based on the experience of the authors for the development of anti-product antibody immunoassays intended for preclinical or clinical studies. While the main focus of this document is assay design considerations, we provide scientific focus and background to the various assay performance parameters necessary for developing a valid assay. Sections on assay performance parameters, including those that appear in regulatory guidances, are contained in this manuscript.
The COVID-19 pandemic has had a heavy impact on daily life, leading to physical and psychosocial consequences. Nowadays, clinicians and health researchers are particularly interested in describing ...and facing the long-term effects of COVID-19, also known as "long-COVID syndrome". Pandemic fatigue has been defined as a cluster of demotivation, tiredness, and psychological effects that emerge gradually over time after the infection or through the adoption of the recommended measures to combat it. In this study, we report the findings of a large survey conducted in South America involving 1448 participants (mean age: 33.9 ± 11.2 years old) from Argentina, Bolivia, Uruguay, Peru, and Paraguay. An online survey was launched through the common social media based on a specific assessment aimed to detect the prevalence of pandemic fatigue and associated factors. Socio-demographic characteristics, medical, and personal information were collected; the Pandemic Fatigue Scale (PFS) and the Coronavirus Anxiety Scale (CAS) were also administered. We found mid-levels of pandemic fatigue among respondents (21.7 ± 7.95 score at PFS) as well as significant anxiety related to the COVID-19 pandemic (1.56 ± 2.76 score at CAS). In addition, pandemic fatigue was significantly associated with the experience of the loss of a relative/friend due to COVID-19, anxiety related to the infection, and reliance on social media as a primary source of information on the pandemic. Vaccination significantly reduced the levels of fatigue among respondents. Our findings may add to the international debate regarding the long-term health consequences of the COVID-19 pandemic and strategies to manage them in the general population of South America.
To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME).
A population approach of ...nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration.
Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration.
A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check.
Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients.
The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis.
The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
The main drawback for the use of heavy silicone oil (HSO) Oxane HD is the difficulties it presents during removal. It differs from conventional silicone oil removal because it progressively ...concentrates in the posterior pole during the removal because of its heavier than water density. We describe a technique to facilitate proper HSO Oxane HD removal and minimize residual posterior bubbles and intraoperative complications. We describe our pearls for removing HSO to obtain the optimal results. A concern associated with HSO is the difficulty it presents when it is removed. However, this can be overcome by appropriate modification of surgical techniques during removal to limit intraoperative complications.
To measure the retinal/choroidal thicknesses in the macular area of asymptomatic pediatric patients with sickle cell disease (SCD).
This cross-sectional cohort study included 40 children (79 eyes) ...with SCD and 19 control patients (36 eyes). All subjects underwent spectral-domain optical coherence tomography (SD-OCT) with enhanced-depth imaging OCT. Generalized Estimating Equations (GEE) were applied to compare the outcomes between groups. P ≤ 0.05 was considered significant.
The choroidal thickness in the macular area in the study subfields was significantly thinner in the SCD eyes compared with control eyes (subfoveal subfield and temporal parafoveal subfield, p < 0.0001; nasal parafoveal subfield, p < 0.0001 temporal perifoveal subfield, p < 0.0001; and nasal perifoveal subfield, p < 0.0001). The variations in the retinal thickness were not significant.
EDI-OCT showed that the macular choroidal thickness is thinner in asymptomatic pediatric patients with SCD.
Neovascular age-related macular degeneration (AMD) is the leading cause of blindness in older adults in the Western world. Ranibizumab (Lucentis
®), a humanized antibody fragment directed against ...vascular endothelial growth factor (VEGF-A), was recently approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. The objective of this study was to characterize the binding affinity and pharmacological activity of ranibizumab for 3 biologically active forms of VEGF-A: VEGF
165, VEGF
121, and VEGF
110. The apparent equilibrium binding affinity of ranibizumab for VEGF-A molecules was determined by Biacore
® analysis; the biological activity of VEGF-A was demonstrated in a human umbilical vein endothelial cell (HUVEC) proliferation–inhibition assay. Inhibition of VEGF-A-induced vascular permeability by ranibizumab was assessed in vivo using hairless guinea pigs and a modified Miles assay. Ranibizumab was capable of binding to recombinant human VEGF
165, VEGF
121, and VEGF
110 (
K
D
≤
192
pM), inhibiting VEGF-A-induced HUVEC proliferation in a concentration-dependent manner. Ranibizumab also exerted potent dose-dependent inhibition (IC
50 of 0.4–1.2
nM) of the vascular permeability-enhancing activity of VEGF
165, VEGF
121, and VEGF
110 in the Miles assay. In conclusion, these results show that ranibizumab is capable of binding to and specifically inhibiting the activities of 3 biologically active forms of VEGF-A. As VEGF-A plays a pivotal role in the pathogenesis of neovascular AMD, ranibizumab activity, as demonstrated in this study, supports its clinical utility in the treatment of this disease.
Describe complications and clinical outcomes of heavy silicone oil (HSO) Oxane HD® use as an alternative to overcome the challenges of performing vitrectomy to treat tractional and rhegmatogenous ...retinal detachments with proliferative vitreoretinopathy (PVR).
A retrospective, observational study was performed on patients from one center from August 2014 to Aug 2023. It was included patients who underwent surgery using HSO Oxane HD® to treat rhegmatogenous retinal detachment with PVR or mixed tractional and rhegmatogenous diabetic retinal detachment. Severely ill patients who could not attend to follow up were excluded. The primary outcome was successful retinal attachment at first postoperative month. A descriptive analysis was performed.
Among the 31 patients, 29 (93.5%) underwent surgeries due to rhegmatogenous retinal detachment and two (6.5%) for diabetic retinal detachment. The primary anatomic success was achieved in 27 (87.1%) patients. At the final visit, 17 (56.6%) had vision better than 20/400 (range, 20/30 to light perception). The vision was stable or improved in 22 (76.8%) patients at the end of follow-up. Nineteen (61.3%) patients required hypotensive eye drops after HSO use and twelve (38.7%) still required hypotensive eye drops at the final follow-up; three (9.7%) patients required additional glaucoma surgeries.
HSO is safe and useful for complex retinal detachments cases specially with inferior tears and PVR. Ocular hypertension is frequent and usually clinically controlled with hypotensive eyedrops. Close postoperatively follow-up is advised due to the ocular complications, particularly elevated intraocular pressure and emulsification.
Mental health symptoms and disorders amongst elite athletes have attracted a great deal of discussion recently. Current epidemiological evidence illustrates that mental health symptoms and disorders ...in elite athletes are prevalent and a concern for athletes, coaches, and sport organizations. Recently, seven consensus, expert, or position statements have been written on the topic of mental health in elite sport. A strategy suggested by each of the seven statements - aimed at preventing and treating mental health symptoms and disorders in elite athletes, both individually and systemically - is to employ education interventions, specifically those based on increasing mental health literacy. Mental health literacy has come to include concepts related to knowledge of effective self-management strategies, challenging mental disorder stigma, awareness and use of mental health first-aid to assist others, and the facilitation of help seeking behaviors. In elite sport, questions remain about how mental health literacy can address the unique needs of the individual athlete, but also factor in their culture and their environment to identify how to prevent and treat mental health symptoms and disorders. The purpose of this commentary is twofold: 1) to explore the evolving concept of mental health literacy within elite sport which addresses individuals, their culture, and their environment, and 2) to propose strategies for best practice and research in mental health literacy within elite sport relying on collaboration between sports psychiatry, sport psychology, and clinical psychology.
Lay summary: Expert statements on mental health in elite sport have suggested the use of educational strategies to address poor mental health in elite athletes. This commentary explores the concept of mental health literacy within elite sport which addresses individuals, their culture, and their environment, and proposes strategies for best practice.
Implications for Practice
Mental health literacy interventions should be based on detailed knowledge of developmental, cultural, and social issues related to sport participation and systemic issues within sport settings and organizations.
Mental health literacy interventions should be designed in a manner which takes due account of cultural issues and contexts, where sport organizational goals are considered while helping organizations recognize and address mental health symptoms and disorders and also create sport environments where individuals can thrive.
Mental health literacy interventions should have measurable impact on both organizations and individuals.
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