59 research outputs found

    Intravitreal Dexamethasone in Patients with Wet Age-Related Macular Degeneration Resistant to Anti-VEGF: A Prospective Pilot Study

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    Purpose. To evaluate the efficacy and safety of a single intravitreal dexamethasone implant (DXI) combined with intravitreal antivascular endothelial growth factor (anti-VEGF) therapy, in patients with neovascular age-related macular degeneration (wet-AMD) resistant to conventional treatment. Methods. In this randomized, controlled pilot study, 16 eyes of 15 patients, unresponsive to anti-VEGF therapy, were enrolled and randomly assigned to two groups: DXI + anti-VEGF (treatment group: 11 eyes) and monthly anti-VEGF alone (control group: 5 eyes). Patients were treated at baseline and followed for 6 months. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) parameters, and fluorescein angiography (FA) were evaluated. Results. Eight eyes (72.7%) in the treatment group and 2 eyes in the control group (40%) showed complete retinal fluid resorption (p=0.049). BCVA showed no significant change from baseline in both the treatment group and the control group (p=0.40 and p=0.29, respectively). Both median central foveal thickness (CFT) and median macular volume showed a greater reduction from baseline in the treatment group. Conclusion. In patients showing an incomplete response to anti-VEGF therapy, DXI combined with intravitreal anti-VEGF seems to improve retinal fluid resorption without functional advantage. This trial is registered with ACTRN12618001102268

    In vivo validation of the adequacy calculator for continuous renal replacement therapies

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    INTRODUCTION: The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting. METHODS: The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (K(CALC)). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (K(DEL)) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data. RESULTS: We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT

    Ocular intracameral pharmacokinetics for a cocktail of timolol, betaxolol and atenolol in rabbits

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    The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three β-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC–MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 μL/min, 687 μL, and 73.87 min), timolol (19.30 μL/min, 937 μL, and 33.64 min), and betaxolol (32.20 μL/min, 1421 μL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow)

    Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail : Tissue exposures in the rabbit eye

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    Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.Peer reviewe

    Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy

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    Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA). Methods: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age. Results: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B). Conclusions: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution

    Trattamento topico della oftalmomiasi esterna da Oestrus ovis: progettazione e sviluppo di un nuovo preparato galenico

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    Introduction Ophthalmomyiasis is an infection of the eye caused by the larvae of Oestrus ovis, Diptera. Currently, there are no available drugs to treat this condition in humans and mechanical removal of the larvae is the only effective therapy. Methods The study was divided into 3 Phases. The first was designed to identify and test “in vitro” new galenic formulation against O. ovis L1 larvae. The second addressed the cytotoxicity of the compounds tested in phase 1 on corneal and conjunctival cells. We assessed the toxicity of different dilutions of Propylene Glycol and then analyzed the combination of Ivermectin with DMSO, Glycol and Glycol + PVP-I. We also tested the 40, 60, 80X dilution of the stock solution. Finally, we tested the compounds in a rat model, in order to assess the in vivo toxicity of the galenic formulations. Results Ivermectin 1% solution and the combination of Ivermectin 1% + PVP-I 0.6% were found to be significantly better than propylene glycol alone, in terms of time needed to kill Larvae (p=0.0422). MTT assay confirmed low tissue toxicity. In the mouse model, no toxicity was found. Conclusion Our results suggest that Ivermectin 1% and Propylene glycol are both effective against L1 larvae and could be potential candidates for the treatment of ophthalmomyiasis caused by Oestrus ovis

    Bromfenac eyedrops in the treatment of diabetic macular edema: a pilot study

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    PurposeTo evaluate the efficacy and safety of topical bromfenac in patients with newly diagnosed diabetic macular edema (DME).MethodsIn this pilot study including 17 patients with monocular, newly ..

    Management of macular oedema in diabetic patients undergoing cataract surgery

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    PURPOSE OF REVIEW: The aim of this study was to describe all the treatment modalities used to prevent and manage macular oedema in diabetic patients undergoing cataract surgery. RECENT FINDINGS: Topical NSAIDs have been proposed to be an effective strategy to prevent postsurgical macular oedema (PME) in diabetic patients. The prophylactic use of intravitreal antivascular endothelial growth factors (anti-VEGF) drugs and steroids in these patients, even if effective, brings some concerns with regard to possible side effects. By contrast, in patients with a diagnosis of diabetic macular oedema (DME) at the time of cataract surgery, intravitreal therapy, both with anti-VEGF drugs and steroids, appears to be the best approach in order to control PME and achieve a good visual outcome. CONCLUSION: All diabetic patients undergoing cataract surgery should be treated with topical NSAIDs to prevent PME. Intravitreal anti-VEGF drugs and steroids, combined with cataract surgery, should be reserved for patients with preexisting DME
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