Comparison of allergy rates in glaucoma patients receiving brimonidine 0.2% monotherapy versus fixed-combination brimonidine 0.2%–timolol 0.5% therapy

ABSTRACT

Objective: To evaluate the incidence of ocular allergy in glaucoma patients prospectively treated with 0.2% brimonidine–0.5% timolol fixed combination (Combigan) compared with the incidence of ocular allergy in patients treated with 0.2% brimonidine (Alphagan?) monotherapy.

Study design and methods: This was a comparative, non-randomized, single-site, interventional study involving patients with primary open-angle glaucoma or exfoliation syndrome who had not previously used brimonidine in any formulation and had no history of ocular allergy. In one study arm, 102 patients were prospectively treated with twice-daily 0.2% brimonidine–0.5% timolol fixed combination. In the other study arm, medical charts at the same center were reviewed to identify a control group of 102 patients who had been treated with twice-daily 0.2% brimonidine monotherapy. Follow-up was at 1, 3, 6, 9, 12, 15, and 18 months of treatment.

Main outcome measure: Ocular allergy defined as the presence of follicles and redness severe enough to warrant discontinuation of the medication.

Results: The incidence of ocular allergy over 18 months of treatment was 8.8% (9/102) in the fixed-combination group compared with 17.6% (18/102) in the brimonidine group (?p?=?0.097). Kaplan–Meier survival analysis suggested that ocular allergy may be reduced or delayed in patients treated with the brimonidine–timolol fixed combination (?p?=?0.066).

Conclusions: The brimonidine–timolol fixed combination was associated with a 50% lower incidence in ocular allergy compared with 0.2% brimonidine monotherapy. This difference between treatments was not statistically significant (?p?=?0.097) but is likely to be clinically important. Additional studies are needed to evaluate the incidence of ocular allergy associated with brimonidine–timolol fixed combination treatment.     

Fixed-combination brimonidine–timolol versus latanoprost in glaucoma and ocular hypertension: a 12-week,randomized, comparison study

Abstract

Objective:

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%–timolol 0.5% compared with latanoprost 0.005% in patients with glaucoma or ocular hypertension.     

Experience with Cosopt,the fixed combination of timolol and dorzolamide,after switch from free combination of timolol and dorzolamide,in Swiss ophthalmologists’ offices

SUMMARY

Purpose: To analyse a response to the therapy switch from the concomitant application of β-blocker and topical carbonic anhydrase inhibitor to the fixed combination of timolol and dorzolamide (Cosopt^*) in glaucoma/ocular hypertensive patients under everyday, office-practice conditions.

Patients and methods: The data source was a survey among practising ophthalmologists in Switzerland assessing their experience with glaucoma patients/ocular hypertensives put for the first time on the fixed combination of timolol and dorzolamide. A total of 98 patients underwent the therapy switch in at least one eye. The intraocular pressure (IOP) change between the baseline visit before switch to the timolol-dorzolamide fixed combination occurred, and the first follow-up control after the switch, served as an indicator of compliance.

Results: The IOP decreased on average from 19.43?±?5.64?mmHg to 17.97?±?3.58?mmHg (p?<?0.01). The time to the follow-up visit ranged from 4 to 354 days, and the magnitude of IOP change demonstrated a significant dependence on the time to the follow-up visit, also when corrected for baseline IOP level. A total of 87 (85.3%) continued on the timolol-dorzolamide fixed combination therapy after the first control visit. In 68 of these 98 patients the contralateral eyes underwent the same therapy switch, and their IOP followed an identical pattern of behaviour.

Conclusion: The average I OP decrease of 1.5?mmHg upon therapy switch to the timolol-dorzolamide fixed combination suggests a better efficacy due to improved compliance. Short-term compliance benefit seems to be more pronounced. The high timolol-dorzolamide fixed combination therapy continuation rate reflects an improvement in compliance and subjectively-perceived convenience.     

Chick chorioallantoic membrane model for in ovo evaluation of timolol maleate–brimonidine tartrate ocular inserts

Abstract

The main aspire of this study was to develop ocular drug delivery system for dual drug glaucoma therapy by timolol maleate–brimonidine tartrate and endeavor the possibility of biocompatibility studies by in ova studies. Matrix type, both hydrophilic and lipophilic polymers, and reservoir-type ocular inserts of timolol maleate were prepared using hydrophilic polymers like polyvinyl alcohol, hydroxyl propyl methyl cellulose K4M and lipophilic polymers like ethylcellulose and eudragit S100 and were optimized. Based on the optimized formulation, triple-layered ocular inserts (reservoir type) of dual drug were prepared by solvent casting technique with an objective of reducing the frequency of administration, obtaining controlled release and greater therapeutic efficacy, preservative free dosage form for the treatment of glaucoma. FTIR spectral studies revealed no pharmaceutical incompatibility and no drug polymer interactions. Maximum drug release (99.18?±?1.7) was achieved when PVP and HPMC K4M in 1:1 ratio with PEG 400 (0.3?ml) drug reservoir layer was sandwiched between ethyl cellulose as rate control membrane up to 32?h in a controlled fashion. Drug release was by non-Fickian diffusion mechanism for single drug formulation. But in dual drug insert, timolol maleate best fit into zero order and for brimonidine tartrate to Higuchi model and diffusion of drugs from this by non-Fickian diffusion mechanism. In ovo studies suggested that the optimized formulation was found to be sterile, biocompatible and physicochemically stable and support us to claim that the developed formulation was biocompatible.     

Adverse events of statin–fenofibric acid versus statin monotherapy: a meta-analysis of randomized controlled trials

Abstract

Background:

Patients with mixed dyslipidemia can benefit from the combination of fenofibric acid (FA) with statins, but concerns about adverse events make physicians reluctant to prescribe the combination therapy.     

Efficacy and safety of ceftazidime–avibactam versus imipenem–cilastatin in the treatment of complicated urinary tract infections,including acute pyelonephritis,in hospitalized adults: results of a prospective,investigator-blinded,randomized study

Abstract

Objectives:

The aim of this prospective phase II, randomized, investigator-blinded study (NCT00690378) was to compare the efficacy and safety of ceftazidime–avibactam and imipenem–cilastatin in hospitalized adults with serious complicated urinary tract infection (cUTI) due to Gram-negative pathogens.     

Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year

Rationale

Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment.

Objectives

The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year.

Method

From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N?=?78), ziprasidone (N?=?62), or quetiapine (N?=?62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.

Results

The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole?=?43.6 %, ziprasidone?=?66.1 % and quetiapine?=?82.3 %) (χ ²?=?22.545; p?<?0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ ²?=?19.436; p?<?0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank?=?30.732 p?<?0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants.

Conclusions

First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.     

Cost comparison of AUC:MIC– versus trough-based vancomycin monitoring for MRSA bacteremia

ObjectivesIt is anticipated that the updated vancomycin monitoring guidelines will reconsider area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC)–based monitoring instead of trough-based monitoring for methicillin-resistant Staphylococcus aureus (MRSA) infections. The AUC:MIC can be estimated using 2 steady-state serum concentrations and first-order pharmacokinetic equations or Bayesian modeling. The cost of AUC:MIC–based monitoring compared with trough-based monitoring is unknown and has been cited as a potential barrier to implementing this monitoring method. The objective of this study was to compare the total vancomycin drug and monitoring cost for patients with MRSA bacteremia who received AUC:MIC– or trough-based monitoring.DesignThis was a single-center, retrospective cohort study.Setting and participantsThis study included patients who were treated for MRSA bacteremia between May 1, 2013 and December 31, 2018, with an 8-month washout period between trough and AUC:MIC–based monitoring at our institution.Outcome measuresThe primary outcome was the aggregate cost of vancomycin therapy, which included the cost associated with sample collection (i.e., supply cost and nursing time), sample analysis (i.e., assay cost and laboratory technician time), result interpretation (i.e., pharmacist time), and drug cost (i.e., cost of total administered vancomycin dose) during the hospital stay.ResultsA total of 52 patients met inclusion criteria with 26 patients in each group. The median (interquartile range) total vancomycin drug and monitoring cost was $338.14 ($235.07–$601.05) for the AUC:MIC–based group compared with $316.79 ($253.36–$520.96) for the trough-based group (P = 0.687).ConclusionVancomycin monitoring using 2 steady-state serum concentrations and first-order pharmacokinetic equations to calculate AUC:MIC was no more costly than a trough-based approach in patients with MRSA bacteremia at our institution.     

Meta-analysis of α2-adrenergic agonists versus carbonic anhydrase inhibitors as adjunctive therapy

Abstract

Objective:

To evaluate the efficacy of α2-adrenergic agonist (AA) brimonidine and topical carbonic anhydrase inhibitors (CAIs) dorzolamide and brinzolamide in reducing intraocular pressure (IOP) when used as adjunctive therapy to β-blockers (BBs) or prostaglandin analogs (PGAs).     

A randomized,cross-over comparison of preference between two reusable insulin pen devices in pen-naïve adults with diabetes

Abstract

Objective:

To evaluate final preference and ease-of-use attributes of two reusable pen injectors, HPS (HumaPen Savvio) and HPL (HumaPen Luxura), in adults with type 1 or type 2 diabetes.     

Esomeprazole and rabeprazole did not reduce antiplatelet effects of aspirin/clopidogrel dual therapy in patients undergoing percutaneous coronary intervention: a prospective,randomized, case–control study

Objectives: Controversy has been prompted based on drug interaction between proton pump inhibitors (PPIs) and aspirin/clopidogrel leading to weakened effects. However, whether such interaction was drug-specific or class effect remains controversial. This study predicted the impact of esomeprazole and rabeprazole on efficacy of dual antiplatelet therapy (DAPT).

Methods: This study, involving 150 patients, evaluated the efficacy of DAPT upon concomitant use of esomeprazole (40 mg/d) or rabeprazole (20 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at day 1, day 3 and day 30 end points after initiation of DAPT.

Results: No significance were observed by post-hoc analysis of treatment-by-period interaction in LTA value and VASP-PRI value when compared with non-PPI users, which suggests no carryover effect in both PPIs over the 30-day treatment period. Moreover, no statistical differences was in LTA or VASP-PRI value in esomeprazole group while rabeprazole group showed decreased in antiplatelet function of DAPT at the day 3 and day 30 end points.

Conclusion: Although antiplatelet effect of DAPT were not affected upon concomitant use of both PPIs over the 30-day treatment period, esomeprazole exerts much more stable impact on antiplatelet effect than rabeprazole among respective end points.     

Exclusive versus dual use of tobacco and electronic cigarettes among adolescents in Poland, 2010–2016

Globally, electronic cigarette (e-cigarette) use among adolescents has increased, along with concerns about potential health implications from exclusive and concurrent tobacco and e-cigarette use (i.e., “dual use”). This study used data from a cross-sectional survey administered to 5708 students aged 15–19 in secondary and technical schools throughout two regions of Poland. Data from 2010–2011 (n = 1760); 2013–2014 (n = 1970) and 2015–2016 (n = 1978) were analyzed to assess changes in use of cigarettes and e-cigarettes from 2010–2016, and correlates of exclusive and dual use, daily use, and intensity of product use from 2013–2016. In this sample, e-cigarette trial and past 30-day exclusive e-cigarette use significantly increased over time (2010–2011: 2%; 2013–2014: 8%; 2015–2016: 11% (p < .05)). Dual use increased from 2010–2011 (4%) to 2013–2014 only (23%, p < .05); and remained stable from 2013–2014 to 2015–2016 (24%, p = .60). Most dual users reported using cigarettes before trying e-cigarettes (82% in 2013–2014, 76% in 2015–2016). Analyses comparing dual users to exclusive users showed significant differences in frequency and intensity of product use, similar findings were observed within dual users. Following the introduction of e-cigarettes, both total tobacco use and total cigarette use increased. Among youth in Poland, e-cigarettes do not seem to replace conventional cigarettes, but instead contribute to a more diverse array of available products from which youth can experiment.     

A randomized,multicentric, comparative evaluation of aceclofenac–paracetamol combination with aceclofenac alone in Indian patients with osteoarthritis flare-up

Objective: To evaluate efficacy and safety of aceclofenac–paracetamol combination against aceclofenac alone in patients with osteoarthritis (OA) flare-up. Methods: This open, randomized, comparative, multicentric, 10-day study enrolled 199 patients (aceclofenac 100 mg + paracetamol 500 mg bid: 101; aceclofenac 100 mg, bid: 98) with painful OA flare-up. Primary efficacy parameters were pain intensity difference (PID), sum of PID (SPID), and peak PID over 4 h (0.5, 1, 2, 4 h) after first dose of study medication. Secondary efficacy measurements were mean pain intensity scores from day 1 to day 10, WOMAC scores, changes in baseline signs and symptoms, and patient's and investigator's overall efficacy assessment. Results: Both treatments showed significant improvement in their baseline values in all efficacy parameters. The combination was superior over monotherapy in terms of PID ( -0.54 vs -0.23, -1.23 vs -0.72, -1.73 vs -1.23 and -1.94 vs -1.43 at 0.5, 1, 2 and 4 h respectively), SPID ( -5.46 vs -3.63) and peak PID ( -2.08 vs -1.56; p < 0.05). At the end of therapy, both treatments were comparable (p > 0.05) with respect to average pain intensity from day 1 to day 10, changes in WOMAC scores and resolution of baseline signs and symptoms. The combination was significantly superior to monotherapy with respect to the patients' and investigators' overall efficacy assessments (p = 0.035 and p = 0.009 respectively). Conclusion: The findings of this open-label, comparative study in Indian patients demonstrates that aceclofenac–paracetamol combination is effective and well tolerated in relieving OA flare-up pain. The combination showed rapid pain relief compared with monotherapy which is desirable by such patients and, hence, this combination can play an important role in the management of acute painful OA flare-up.