A Study of the Safety and Efficacy of Travoprost 0.004%/Timolol 0.5% Ophthalmic Solution Compared to Latanoprost 0.005% and Timolol 0.5% Dosed Concomitantly in Patients with Open-Angle Glaucoma or Ocular Hypertension

Background/Aims: To compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% in fixed combination with the unfixed combination of latanoprost 0.005% and timolol 0.5% in open-angle glaucoma or ocular hypertension patients with IOP levels below 18 mmHg on the unfixed combination of latanoprost 0.005% and timolol 0.5%. Methods: Following a 30-day open-label run-in with latanoprost QD PM and timolol QD AM, subjects with intraocular pressure below 18 mmHg were randomized to continue concomitant latanoprost QD PM and timolol QD AM or switch to travoprost 0.004%/timolol 0.5% QD AM and vehicle QD PM in masked fashion and were followed for 3 months. The primary efficacy endpoint was mean IOP reduction from baseline. Results: There were no clinically relevant or statistically significant differences in mean IOP, mean IOP change from baseline, or percentage IOP change from baseline between the two treatment groups. Between-group differences in mean IOP were within ±0.3 mmHg at all time points (p ≥ 0.384), and between-group differences in mean IOP change from baseline were within ±0.4 mmHg at all time points. Overall, 88% of patients whose IOP was less than 18 mmHg on the unfixed combination of latanoprost and timolol remained well controlled on the same regimen in the masked portion of the study, compared with 92% who remained well controlled after switching to travoprost/timolol. Conclusion: Travoprost 0.004%/timolol 0.5% administered once daily and concomitant administration of timolol 0.5% and latanoprost 0.005% produce similar maintenance of IOP-lowering effect in patients who were previously well controlled on concomitant administration of latanoprost and timolol. Patients who are well controlled on latanoprost and timolol concomitant therapy can be switched to once-daily therapy with travoprost 0.004%/timolol 0.5% with no expected compromise in the safety and efficacy of their treatment

A study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to latanoprost 0.005% and timolol 0.5% dosed concomitantly in patients with open-angle glaucoma or ocular hypertension

Douglas J Rhee1, James H Peace2, Sushanta Mallick3, Theresa A Landry3, Michael VW Bergamini3, and the Study Group*1Massachusetts Eye and Ear Infirmary, Harvard University, Boston, MA, USA; 2Diabetic Eye Medical Clinic, Inglewood, CA, USA; 3Alcon Laboratories, Inc., Ft. Worth, TX, USA; *Study Group members listed in AppendixBackground/Aims: To compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% in fixed combination with the unfixed combination of latanoprost 0.005% and timolol 0.5% in open-angle glaucoma or ocular hypertension patients with IOP levels below 18 mmHg on the unfixed combination of latanoprost 0.005% and timolol 0.5%.Methods: Following a 30-day open-label run-in with latanoprost QD PM and timolol QD AM, subjects with intraocular pressure below 18 mmHg were randomized to continue concomitant latanoprost QD PM and timolol QD AM or switch to travoprost 0.004%/timolol 0.5% QD AM and vehicle QD PM in masked fashion and were followed for 3 months. The primary efficacy endpoint was mean IOP reduction from baseline.Results: There were no clinically relevant or statistically significant differences in mean IOP, mean IOP change from baseline, or percentage IOP change from baseline between the two treatment groups. Between-group differences in mean IOP were within ±0.3 mmHg at all time points (p ≥ 0.384), and between-group differences in mean IOP change from baseline were within ±0.4 mmHg at all time points. Overall, 88% of patients whose IOP was less than 18 mmHg on the unfixed combination of latanoprost and timolol remained well controlled on the same regimen in the masked portion of the study, compared with 92% who remained well controlled after switching to travoprost/timolol.Conclusion: Travoprost 0.004%/timolol 0.5% administered once daily and concomitant administration of timolol 0.5% and latanoprost 0.005% produce similar maintenance of IOP-lowering effect in patients who were previously well controlled on concomitant administration of latanoprost and timolol. Patients who are well controlled on latanoprost and timolol concomitant therapy can be switched to once-daily therapy with travoprost 0.004%/timolol 0.5% with no expected compromise in the safety and efficacy of their treatment.Keywords: travoprost, timolol, glaucoma, intraocular pressure, fixed combinatio

An improved synthesis, crystal structures, and metallochromism of salts of [Ru(tolyl-terpy)(CN)(3)](-)

The previously reported complex [Ru(ttpy)(CN)(3)] [ttpy = 4'(p-tolyl)-2,2':6',2"-terpyridine] is conveniently synthesised by reaction of ttpy with Ru(dmso)(4)Cl-2 to give [Ru(ttpy)(dmso)Cl-2], which reacts in turn with KCN in aqueous ethanol to afford [Ru(ttpy)(CN)(3)] which was isolated and crystallographically characterised as both its (PPN)(+) and K+ salts. The K+ salt contains clusters containing three complex anions and three K+ cations connected by end-on and side-on cyanide ligation to the K+ ions. The solution speciation behaviour of [Ru(ttpy)(CN)(3)] was investigated with both Zn2+ and K+ salts in MeCN, a solvent sufficiently non-competitive to allow the added metal cations to associate with the complex anion via the externally-directed cyanide lone pairs. UV-Vis spectroscopic titration of (PPN)[Ru(ttpy)(CN)(3)] with Zn(ClO4)(2) showed a blue shift of 2900 cm (1) in the (MLCT)-M-1 absorption manifold due to the ` metallochromism' effect; a series of distinct binding events could be discerned corresponding to formation of 4:1, 1:1 and then 1:3 anion: cation adducts, all with high formation constants, as the titration proceeded. In contrast titration of (PPN)[Ru(ttpy)(CN)(3)] with the more weakly Lewis-acidic KPF6 resulted in a much smaller blue-shift of the 1MLCT absorptions, and the titration data corresponded to formation of 1:1 and then 2: 1 cation: anion adducts with weaker stepwise association constants of the order of 10(4) and then 10(3) M (1). Although association of [Ru(ttpy)(CN)(3)] resulted in a blue-shift of the (MLCT)-M-1 absorptions, the luminescence was steadily quenched, as raising the (MLCT)-M-3 level makes radiationless decay via a lowlying (MC)-M-3 state possible. (C) 2010 Elsevier B. V. All rights reserved

Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial.

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy. METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration. CONCLUSIONS: AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP

Bryophytes of Europe Traits (BET) dataset: a fundamental tool for ecological studies

Bryophytes are a diverse group of organisms with unique properties, yet they are severely underrepresented in plant trait databases. Building on the recently published European Red List of bryophytes and previous trait compilations, we present the Bryophytes of Europe Traits (BET) data set, including biological traits such as those related to life history, growth habit, sexual and vegetative reproduction; ecological traits such as indicator values, substrate and habitat; and bioclimatic variables based on the species' European range. The data set includes values for 65 traits and 25 bio-climatic variables, containing more than 135,000 trait values with a completeness of 82.7% on average. The data set will enable future studies in bryophyte biology, ecology and conservation, and may help to answer fundamental questions in bryology.info:eu-repo/semantics/publishedVersio

QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting.

To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania. Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting

European multidisciplinary tumor boards support cross-border networking and increase treatment options for patients with rare gynecological tumors.

peer reviewed[en] OBJECTIVE: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies. METHODS: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials. All G2 healthcare providers were invited to participate in monthly multidisciplinary meetings. Patient data were collected using a standardized form and case summaries were distributed before each meeting. After each tumor board, a meeting summary with treatment recommendations was sent to all participants and the project manager at the coordinating center. The multidisciplinary tumor board format and outcomes were regularly discussed at G2 domain meetings. Anonymized clinical data and treatment recommendations were registered in a prospective database. For this report, clinical data were collected between November 2017 and December 2020 and follow-up data retrieved until May 2021. RESULTS: During the 3-year period, 31 multidisciplinary tumor boards were held with participants from 10 countries and 20 centers. 91 individual patients were discussed between one and six times for a total of 109 case discussions. Follow-up data were retrieved from 64 patients and 80 case discussions. Adherence to treatment recommendations was 99%. Multidisciplinary tumor board recommendations resulted in 11 patients getting access to off-label treatment and one patient being enrolled in a clinical trial in another European country. 14/91 patients were recommended for surveillance only when additional treatment had been considered locally. CONCLUSION: Cross-border multidisciplinary tumor boards enable networking and clinical collaboration between healthcare professionals in different countries. Surveillance strategies, off-label drug use, and increased participation in clinical trials are possible benefits to patients with rare gynecological tumors

A novel neuroprotective therapy for Parkinson's disease using a viral noncoding RNA that protects mitochondrial complex I activity.

Parkinson's disease (PD) is a neurodegenerative disorder that results in the loss of nigrostriatal dopamine neurons. The etiology of this cell loss is unknown, but it involves abnormalities in mitochondrial function. In this study, we have demonstrated that the administration of a novel noncoding p137 RNA, derived from the human cytomegaloviral β2.7 transcript, can prevent and rescue dopaminergic cell death in vitro and in animal models of PD by protecting mitochondrial Complex I activity. Furthermore, as this p137 RNA is fused to a rabies virus glycoprotein peptide that facilitates delivery of RNA across the blood-brain barrier, such protection can be achieved through a peripheral intravenous administration of this agent after the initiation of a dopaminergic lesion. This approach has major implications for the potential treatment of PD, especially given that this novel agent could have the same protective effect on all diseased neurons affected as part of this disease process, not just the dopaminergic nigrostriatal pathway

Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization

Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected macaques, whereas natural reservoir hosts exhibit limited disease and pathology. It is, however, unclear how natural hosts can sustain high viral loads, comparable to those observed in the pathogenic model, without developing severe disease. We performed transcriptional profiling on lymph node, blood, and colon samples from African green monkeys (natural host model) and Asian pigtailed macaques (pathogenic model) to directly compare gene expression patterns during acute pathogenic versus non-pathogenic SIV infection. The majority of gene expression changes that were unique to either model were detected in the lymph nodes at the time of peak viral load. Results suggest a shift toward cellular stress pathways and Th1 profiles during pathogenic infection, with strong and sustained type I and II interferon responses. In contrast, a strong type I interferon response was initially induced during non-pathogenic infection but resolved after peak viral load. The natural host also exhibited controlled Th1 profiles and better preservation of overall cell homeostasis. This study identified gene expression patterns that are specific to disease susceptibility, tissue compartmentalization, and infection duration. These patterns provide a unique view of how host responses differ depending upon lentiviral infection outcome