Safety and efficacy of travoprost solution for the treatment of elevated intraocular pressure

Travoprost is a prostaglandin analogue widely used for reducing intraocular pressure (IOP) in patients affected with glaucoma and ocular hypertension. It exerts its ocular hypotensive effect through the prostaglandin FP receptors, located in the ciliary muscle and the trabecular meshwork. Several studies have shown that topical administration of travoprost induces a mean IOP reduction ranging from 25% to 32%, and sustained throughout the 24-hour cycle. When compared with timolol, travoprost is more effective at reducing IOP, while generally no difference has been found in the head-to-head comparison with other prostaglandin analogues. The fixed combination of travoprost and timolol has demonstrated a hypotensive efficacy comparable to the concomitant administration of the two drugs. Recently, a new preservative-free formulation of travoprost 0.004% has been marketed for reducing tolerability-related problems in subjects affected with ocular surface disease. Low rates of topical and systemic adverse reactions, strong ocular hypotensive efficacy, and once-a-day dosing make travoprost a first-line treatment for patients affected with elevated IOP

Evaluating the effect of pupil dilation on spectral-domain optical coherence tomography measurements and their quality score

BACKGROUND: Spectral-domain optical coherence tomography (SD-OCT) provides fast scan speed and high scan resolution improving its diagnostic accuracy. The purpose of this study was to evaluate if SD-OCT measurements and their quality score are influenced by pupil dilation. METHODS: Retinal nerve fiber layer thickness (RNFL), ganglion cell complex (GCC) and optic nerve head (ONH) were measured in one eye of 57 glaucoma patients and 36 healthy subjects using spectral domain optical coherence tomography (SD-OCT) before and after pupil dilation. Comparisons were made between measurements and their quality score pre- and post dilation (Signal Strength Index, SSI). Overall RNFL, average GCC and ONH rim volume were considered in the analysis. RESULTS: No statistically significant differences were found between pre- and post-dilation measurements in both groups (glaucoma: RNFL 80 ± 15 μm vs 80 ± 16 μm, p = 0.87; GCC 81.35 ± 13.4 μm vs 81.10 ± 13.14 μm, p = 0.92; ONH 0.05 ± 0.11 mm(3) vs 0.04 ± 0.07 mm(3), p = 0.74; controls RNFL 99 ± 12 μm vs 98 ± 14 μm, p = 0.70; GCC 92.12 ± 6.7 μm vs 91.54 ± 7.05 μm, p = 0.72; ONH 0.11 ± 0.1 mm(3) vs 0.04 ± 0.07 mm(3), p = 0.36) nor between pre- and post-dilation quality score (glaucoma SSI RNFL 54.3 ± 10.3 vs 51.7 ± 18.1, p = 0.12; SSI GCC 58 ± 9.5 vs 57 ± 8.09, p = 0.55; SSI ONH 48.5 ± 7.6 vs 46.6 ± 7.2, p = 0.16; controls SSI RNFL 57 ± 10.3 vs 54 ± 9.31, p = 0.2; SSI GCC 60.9 ± 8.1 vs 58.8 ± 7.3, p = 0.3; SSI ONH 51.5 ± 8.9 vs 50.4 ± 8.3, p = 0.59). CONCLUSION: Pupil dilation doesn’t affect SD-OCT measurements and their quality score

Levels of plasma homocysteine in pseudoexfoliation glaucoma.

BACKGROUND: To examine levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with pseudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and healthy control subjects. METHODS: This study included 36 patients with PEXG, 40 with POAG, and 40 age-matched healthy subjects. Fasting plasma Hcy concentrations and levels of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay; values exceeding 14 μm/l were considered elevated. RESULTS: Mean plasma Hcy was significantly higher in PEXG (16.55 ± 7.23 μm/l) compared with POAG (13.91 ± 3.61 μm/l) and controls (13.12 ± 5.13 μm/l) (p = 0.03 and p = 0.0007 respectively). There were no statistical differences in serum vitamin B12 and folic acid levels among PEXG, POAG and control subjects (p > 0.05). A moderate, although statistically significant, relationship between Hcy and folic acid levels was found in the PEXG group (R(2) = 0.23, p = 0.003). Hcy levels were found not to be related with folic acid or vitamin B12 in either POAG or control subjects. CONCLUSIONS: In this study, plasma Hcy is significantly higher in PEXG group than the POAG and control groups. Hyper-Hcy might play a role in the pathogenesis of PEXG. Hyper-Hcy may be an independent factor stressing vasculopathy in addition to pseudoexfoliation, so might be a modifiable risk factor for PEXG

Systemic perfusion at peak incremental exercise in left ventricular assist device recipients: Partitioning pump and native left ventricle relative contribution

AbstractBackgroundIn continuous-flow left ventricular assist device (LVAD) recipients, little is known about the relative pump- and left ventricle-generated blood flow (PBF and LVBF, respectively) contribution to peak systemic perfusion during incremental exercise and about how PBF/LVBF interplay and exercise capacity may be affected by pump speed increase.MethodsTwenty-two LVAD recipients underwent ramp cardiopulmonary exercise tests at fixed and increasing pump speed (+ 1.5% of baseline speed/10 W workload increase), echocardiography and NT-proBNP dosage. Peak systemic perfusion was peak VO2/estimated peak arterio-venous O2 difference, and LVBF was systemic perfusion minus PBF provided by LVAD controller. A change of peak percentage of predicted VO2max (Δpeak%VO2) ≥ 3 in increasing- vs. fixed-speed test was considered significant.ResultsTricuspid annular plane systolic excursion (TAPSE) and NT-proBNP were significantly lower and higher, respectively, in Δpeak%VO2 13 mm as a predictor of Δpeak%VO2 ≥ 3.ConclusionsA significant LVBF contribution to peak systemic perfusion and pump speed increase-induced peak VO2 improvement was detectable only in patients with a more preserved right ventricular systolic function and stable hemodynamic picture. These findings should be taken into consideration when designing LVAD controllers aiming to increase pump speed according to increasing exercise demands

An immunohistochemical study of the human periodontal ligament during sperimental orthodontic movement

Orthodontic tooth movement is characterized by remodeling changes in dental and paradental tissues, including dental pulp, periodontal ligament (PDL), alveolar bone, and gingiva. These tissues, when exposed to varying degrees of magnitude, frequency, and duration of mechanical loading, express macroscopic and microscopic changes. The different modification of periodontal ligament during load deformation can be monitored by analysis of the expression of different collagen types, fibronectin and vascular endothelial growth factor. The aim of this study was to evalue PDL collagen types I and IV, fibronectin and vascular endothelial growth factor (VEGF) modification induced by application of a precalibrated and constant orthodontic strength at different stages of treatment. For the study we utilized a coilspring NiTi 50 gr. and in vivo samples of 20 maxillaries and mandibular premolars of patients aged from 13 to 18 years subject to orthodontic treatment. These teeth was extracted at 1, 7, 14, 21 and 28 days from application of force respectively. The extraction of the PDL was effectuated scarifying the radicular surface on the pressure and tension side. The results were compared with periodontal ligament samples of the normal homologous teeth (control). The periodontal ligament samples were fixed in 3% paraformaldehyde in a 0,2M phosphate buffer at pH 7,4. The following primary antibodies were used: anti collagen I, anti collagen IV, anti fibronectin and mouse monoclonal anti-VEGF. Section were then observed and photographed using Zeiss LSM 510 confocal microscope. Were analyzed fluorescence intensity and compared with the control side. The signal of type I collagen is negative in tension and pressure side after 1 day, showed an increased respect to control, in the tension and pressure side, until 7, 14 and 21 days. After this stage in both sides maintained the same values of the control. The immunofluorescence of type IV collagen is negative, in both sides, after 1 and 7 days. At 14, 21 and 28 days from treatment, increased gradually in pressure side and manteined the same values of the control in tension side. The observation of fibronectin showed strongly immunofluorescence at all stages of treatment. After 1, 7 and 14 days the immunofluorescence of VEGF is negative in pressure side, and positive in tension side. In the last observation periods at 21 and 28 days, VEGF signal showing, in both sides, significant increase when compared with the control group. These findings suggest that: the increase of collagen type I and fibronectin could indicate that the solicitation by orthodontic force could determinate an increase of metabolic activity in the periodontal ligament. The rapid modification after the start of tooth movement, suggest that VEGF may be involved in the early stages of periodontal remodeling during orthodontic tooth movement, when occur rapid changes in local blood circulation. The initial decrease of collagen type IV, indicate a loss of vascular component in the early stages of movement infact this protein is localized in perivessel zones

Aggregate Farming in the Cloud: The AFarCloud ECSEL project

Farming is facing many economic challenges in terms of productivity and cost-effectiveness. Labor shortage partly due to depopulation of rural areas, especially in Europe, is another challenge. Domain specific problems such as accurate monitoring of soil and crop properties and animal health are key factors for minimizing economical risks, and not risking human health. The ECSEL AFarCloud (Aggregate Farming in the Cloud) project will provide a distributed platform for autonomous farming that will allow the integration and cooperation of agriculture Cyber Physical Systems in real-time in order to increase efficiency, productivity, animal health, food quality and reduce farm labor costs. Moreover, such a platform can be integrated with farm management software to support monitoring and decision-making solutions based on big data and real-time data mining techniques.publishedVersio

Blindness and glaucoma: A multicenter data review from 7 academic eye clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (''controls''). Blindness was defined as visual acuity-0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6%at the beginning, and 15.5%and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years)//conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14%in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved//it could be predicted by high initial MD, high initial IOP, and old age

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707