ABSTRACT
PRCIS: Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed. PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). DESIGN: Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. METHODS: Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. RESULTS: The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 and -9.47±3.06 mm Hg, respectively, at 8 am , -9.41±3.03 and -9.19±3.12 mm Hg at 10 am , and -8.99±3.36 and -8.54±3.44 mm Hg at 4 pm . Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5 mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively). CONCLUSIONS: PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.
Subject(s)
Antihypertensive Agents , Bimatoprost , Gels , Glaucoma, Open-Angle , Intraocular Pressure , Ocular Hypertension , Ophthalmic Solutions , Preservatives, Pharmaceutical , Tonometry, Ocular , Humans , Bimatoprost/administration & dosage , Intraocular Pressure/drug effects , Intraocular Pressure/physiology , Female , Male , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Middle Aged , Aged , Preservatives, Pharmaceutical/administration & dosage , Glaucoma, Open-Angle/drug therapy , Glaucoma, Open-Angle/physiopathology , Ocular Hypertension/drug therapy , Ocular Hypertension/physiopathology , Ophthalmic Solutions/administration & dosage , Treatment Outcome , Adult , Double-Blind Method , Aged, 80 and over , Hyperemia/chemically inducedABSTRACT
BACKGROUND: Post-occlusive reactive hyperemia (PORH) typically requires caffeine abstinence. For habitual users, it is unknown if abstinence affects PORH. OBJECTIVE: Compare PORH after habitual users consume or abstain from caffeine. METHODS: On separate visits (within-subject), PORH was measured in 30 participants without abstinence from typical caffeine doses (CAFF) and with abstinence (ABS). Measurements included baseline and peak hyperemic velocity, tissue saturation index slopes during ischemia (Slope 1) and following cuff deflation (Slope 2), resting arterial occlusion pressure (AOP), heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure. All variables were compared using Bayesian paired t-tests. BF10â=âlikelihood of alternative vs null. Results are mean±SD. RESULTS: Comparing baseline velocity (cm/s) between CAFF (9.3±4.8) and ABS (7.5±4.9) yielded anecdotal evidence (BF10â=â1.0). Peak hyperemic velocity (cm/s) was similar (CAFFâ=â77.3±16.7; ABSâ=â77.6±19.0, BF10â=â0.20). For slopes (TSI% /s), CAFF Slope 1â=â-0.11±0.04 and Slope 2â=â1.9±0.46 were similar (both BF10≤0.20) to ABS Slope 1â=â-0.12±0.03 and Slope 2â=â1.8±0.42. SBP and DBP (mmHg) were both similar (CAFF SBPâ=â116.0±9.8, DBPâ=â69.6±5.8; ABS SBPâ=â115.5±10.7, DBPâ=â69.5±5.4; both BF10≤0.22). Comparing AOP (mmHg) (CAFFâ=â146.6±15.0; ABSâ=â143.0±16.4) yielded anecdotal evidence (BF10â=â0.46). HR (bpm) was similar (CAFFâ=â66.5±12.3; ABSâ=â66.9±13.0; BF10â=â0.20). CONCLUSIONS: In habitual users, consuming or abstaining from typical caffeine doses does not appear to affect post-occlusive reactive hyperemia.
Subject(s)
Caffeine , Hyperemia , Humans , Hyperemia/chemically induced , Caffeine/administration & dosage , Caffeine/adverse effects , Male , Female , Adult , Blood Flow Velocity/drug effects , Blood Pressure/drug effectsABSTRACT
PURPOSE: The aim of this study was to demonstrate the efficacy of cyclosporine A 0.1% cationic emulsion (CsA CE) eye drops 4 times a day in pediatric patients affected by a moderate form of vernal keratoconjunctivitis (VKC). METHODS: This was a prospective study of pediatric patients, aged 5-16 years, with an active moderate form of VKC who were poor responders to topical antihistamines treatment and were treated 4 times a day with CsA CE. The clinical signs were graded for analysis as follows: hyperemia, tarsal papillae, and limbal papillae. RESULTS: Twenty-eight patients (22 males and 6 females) with a minimum follow-up period of 3 months were included in the analysis. Statistical analysis excluded tarsal papillae because of the very low baseline value. The clinical score of hyperemia and limbal papillae improved from the first evaluation and was maintained over the follow-up. No side effects were noted. CONCLUSION: CsA CE has been proposed as a treatment for severe forms of VKC. This study has shown that administration 4 times a day is also effective in the treatment of moderate forms of VKC in children.
Subject(s)
Conjunctivitis, Allergic , Hyperemia , Male , Female , Humans , Child , Cyclosporine , Conjunctivitis, Allergic/drug therapy , Conjunctivitis, Allergic/diagnosis , Immunosuppressive Agents , Prospective Studies , Emulsions/therapeutic use , Hyperemia/chemically induced , Hyperemia/drug therapy , Ophthalmic SolutionsABSTRACT
OBJECTIVE: To compare objective ocular redness measured using OCULUS Keratograph 5â M before and after 0.2% brimonidine instillation in glaucoma patients under topical hypotensive treatment. METHODS: 60 eyes from 60 subjects diagnosed with glaucoma or ocular hypertension under hypotensive ocular topical treatment were analyzed. Basal Ophthalmological examination was performed.Outcome variables were OCULUS Keratograph 5â M redness scores (RS) before and after 0.2% brimonidine instillation; overall, bulbar temporal (BT), bulbar nasal (BN), limbar temporal (LT), and limbar nasal (LN); non-invasive average tear film breakup time (Nia-BUT), non-invasive first tear film breakup time (Nif-BUT) and meibography. In addition, the following clinical data were collected: intraocular pressure, type, duration, amount, and preservatives/or not of hypotensive treatment, fluorescein corneal staining score and lower tear meniscus height. RESULTS: All eyes were under topical medication. All redness scores were reduced after brimonidine instillation, mean RS differences were BT 0.82 ± 0.62, BN hyperemia 1.03 ± 0.55, LN hyperemia 0.84 ± 0.49, LT hyperemia 0.71 ± 0.50 and total hyperemia 0.91 ± 0.52 (all p < 0.001). 30â min after brimonidine instillation mean overall RS reduction was 47.97 ± 12.39% (p < 0.001) and after 1â h there was a persistent reduction of overall RS of 45.92 ± 14.27% (p < 0.001). Hyperemia reduction was significant and comparable between preservative and preservative-free group 0.12 ± 0.14 (p > 0.392) and between patient with combination therapy and monotherapy 0.16 ± 0.14 (p > 0.258). CONCLUSION: A significant reduction of conjunctival hyperemia was objectively found in glaucoma patients under topical hypotensive treatment before and after brimonidine instillation. Its fast and long-lasting effect may be useful preoperatively in glaucoma patients to reduce intraoperative bleeding and associated complications.
Subject(s)
Glaucoma , Hyperemia , Ocular Hypertension , Humans , Brimonidine Tartrate/therapeutic use , Hyperemia/chemically induced , Hyperemia/diagnosis , Hyperemia/drug therapy , Ophthalmic Solutions/therapeutic use , Glaucoma/drug therapy , Ocular Hypertension/drug therapy , Intraocular Pressure , Preservatives, Pharmaceutical/adverse effects , Antihypertensive Agents/therapeutic useABSTRACT
INTRODUCTION: Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α2-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine. METHODS: This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC â ripasudil â brimonidine (group A), ripasudil â brimonidine â RBFC (group B), or brimonidine â RBFC â ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics. RESULTS: Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC. CONCLUSION: RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC. TRIAL REGISTRATION: Japan Registry of Clinical Trials; Registration No. jRCT2080225220.
Subject(s)
Glaucoma, Open-Angle , Hyperemia , Ocular Hypertension , Male , Adult , Humans , Brimonidine Tartrate/pharmacology , Brimonidine Tartrate/therapeutic use , Glaucoma, Open-Angle/drug therapy , Ocular Hypertension/drug therapy , Prospective Studies , Hyperemia/chemically induced , Hyperemia/drug therapy , Endothelial Cells , Intraocular Pressure , Ophthalmic Solutions/therapeutic use , Antihypertensive Agents/therapeutic use , Quinoxalines/adverse effectsABSTRACT
AIMS: Systemic venous congestion is associated with an increased risk of acute kidney injury (AKI) in critically ill patients. Venous Excess Ultrasound Score (VExUS) has been proposed as a non-invasive score to assess systemic venous congestion. We aimed to evaluate the association between VExUS and AKI in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: This is a prospective study including patients with the diagnosis of ACS (both ST elevation and non-ST elevation ACS). VExUS was performed during the first 24 h of hospital stay. Patients were classified according to the presence of systemic congestion (VExUS 0/≥1). The primary objective of the study was to determine the occurrence of AKI, defined by KDIGO criteria. A total of 77 patients were included. After ultrasound assessment, 31 (40.2%) patients were categorized as VExUS ≥1. VExUS ≥1 was more frequently found in inferior vs. anterior myocardial infarction/non-ST-segment elevation acute myocardial infarction (48.3 vs. 25.8 and 22.5%, P = 0.031). At each increasing degree of VExUS, a higher proportion of patients developed AKI: VExUS = 0 (10.8%), VExUS = 1 (23.8%), VExUS = 2 (75.0%), and VExUS = 3 (100%; P < 0.001). A significant association between VExUS ≥1 and AKI was found [odds ratio (OR): 6.75, 95% confidence interval (CI): 2.21-23.7, P = 0.001]. After multivariable analysis, only VExUS ≥1 (OR: 6.15; 95% CI: 1.26-29.94, P = 0.02) remained significantly associated with AKI. CONCLUSION: In patients hospitalized with ACS, VExUS is associated with the occurrence of AKI. Further studies are needed to clarify the role of VExUS assessment in patients with ACS.
Subject(s)
Acute Coronary Syndrome , Acute Kidney Injury , Hyperemia , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/diagnostic imaging , Risk Factors , Prospective Studies , Hyperemia/chemically induced , Hyperemia/complications , Treatment Outcome , ST Elevation Myocardial Infarction/complications , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Myocardial Infarction/complications , Percutaneous Coronary Intervention/adverse effects , Contrast Media/adverse effectsABSTRACT
Sore throat is one of the most frequent complaints with which patients seek medical help from an otorhinolaryngologist, therapist and pediatrician. OBJECTIVE: To evaluate the efficacy and safety of a combined topical drug with flurbiprofen and cetylpyridinium chloride compared with a monocomponent drug in patients with sore throat associated with manifestations of acute pharyngitis, tonsillitis or with exacerbation of chronic forms of pharyngitis or tonsillitis. MATERIAL AND METHODS: A prospective, multicenter, open, randomized, comparative study in parallel groups included 266 adult patients aged 18 to 60 years with an established diagnosis of acute pharyngitis or acute tonsillitis with the main complaint of sore throat caused by viral infections of the upper respiratory tract. The patients included in the study were randomized into two groups of 133 participants each: the 1st group included patients who received the combined agent flurbiprofen 8.75 mg and cetylpyridinium chloride 1.0 mg in the form of tablets for resorption; the 2nd group included patients who received cetylpyridinium chloride 1.2 mg in the form of medicinal lozenges. The effectiveness was evaluated on three scales - STPIS, TPA, STPR, reflecting indicators of the dynamics of the disease. RESULTS: The studied combination turned out to be more effective than the monocomponent remedy and was characterized by a more pronounced decrease in the intensity of sore throat within 2 hours after taking the drug and a decrease in pharyngeal hyperemia. CONCLUSION: According to results of the study, the use of a drug based on the combination of flurbiprofen and cetylpyridinium chloride was accompanied by a rapid and pronounced decrease in the intensity of sore throat and pharyngeal hyperemia in patients with upper respiratory tract infections.
Subject(s)
Flurbiprofen , Hyperemia , Pharyngitis , Tonsillitis , Humans , Adult , Flurbiprofen/adverse effects , Cetylpyridinium , Prospective Studies , Hyperemia/chemically induced , Hyperemia/complications , Pain Measurement , Double-Blind Method , Treatment Outcome , Pharyngitis/diagnosis , Pharyngitis/drug therapy , Pharyngitis/etiology , Pain , Tonsillitis/diagnosis , Tonsillitis/drug therapy , Tonsillitis/etiologyABSTRACT
INTRODUCTION: Allergic conjunctivitis is an immune-mediated inflammatory disease of the conjunctiva that is induced by antigens. Allergic conjunctivitis can cause various symptoms such as ocular itching, hyperemia and edema. Developing experimental animal models that show clinical symptoms and methods for quantitative and objective evaluation is important for understanding allergic conjunctivitis. Therefore, this study aimed to develop an ovalbumin (OVA)-induced mouse model of allergic conjunctivitis and a useful method for evaluating symptoms of allergic conjunctivitis. METHODS: ICR mice were sensitized by an intraperitoneal injection of OVA in PBS containing alum on days 0 and 5. Subsequently, local sensitization was then performed once daily from days 14 to 28, by instilling OVA in PBS into the both eyes. Drug treatment was administered once daily from days 14 to 28. Mice were randomly assigned topical treatment groups: Group 1, 0.1% betamethasone; Group 2, 0.025% levocabastine; Group 3 PBS (control). RESULTS: Mice showed marked eye scratching behavior, hyperemia, edema, infiltration of eosinophils into tears and increased antigen-specific immunoglobulin E antibody levels in tears and the serum. These symptoms were inhibited by instillation of levocabastine and betamethasone, which are used clinically for the treatment of allergic conjunctivitis. DISCUSSION: This method may be useful for evaluation of the symptoms of allergic conjunctivitis in experimental and clinical settings. In particular, the developed method, which measures the number of eosinophils in tears collected with phenol red threads, may enable the quantitative, objective, and noninvasive evaluation of the severity of allergic conjunctivitis.
Subject(s)
Conjunctivitis, Allergic , Hyperemia , Mice , Animals , Conjunctivitis, Allergic/chemically induced , Conjunctivitis, Allergic/drug therapy , Eosinophils , Hyperemia/chemically induced , Mice, Inbred ICR , Disease Models, Animal , Ovalbumin , Immunoglobulin E , Edema , Betamethasone/adverse effectsABSTRACT
INTRODUCTION: Ocular redness, or conjunctival hyperemia, is a common ophthalmic sign associated with reduced quality of life. For redness without apparent underlying pathology, topical ophthalmic decongestants have been widely used. AREAS COVERED: Brimonidine tartrate was approved in 2017 as a topical vasoconstrictor at a 0.025% concentration for relief of ocular redness. Since then, investigators have reported on efficacy and safety findings from studies evaluating low-dose brimonidine for reducing ocular redness. EXPERT OPINION: Brimonidine is highly selective for α2-adrenergic receptors. Clinical trials have so far shown that the drug in low doses significantly reduces ocular redness in comparison to vehicle for up to 8 hours. Brimonidine-treated eyes did not present side effects of other vasoconstrictors, such as hypotension, cardiac arrhythmia, or drowsiness. Ocular adverse events, such as allergic reactions and redness rebound, were also minimal. In this review, we examine in detail published literature on the mechanism of brimonidine tartrate and its efficacy and safety in relieving conjunctival hyperemia.
Subject(s)
Hyperemia , Adrenergic alpha-Agonists , Brimonidine Tartrate/adverse effects , Erythema/drug therapy , Humans , Hyperemia/chemically induced , Hyperemia/drug therapy , Nasal Decongestants , Ophthalmic Solutions/adverse effects , Quality of Life , Quinoxalines/adverse effects , Receptors, AdrenergicABSTRACT
BACKGROUND: Fractional flow reserve (FFR) is routinely used to evaluate coronary stenosis in patients with atrial fibrillation (AF), although no studies currently address its reliability in this particular population. The clinical impact of correct assessment of coronary stenosis in AF is particularly high in light of the antithrombotic therapy imposed by both AF and coronary stenting. OBJECTIVES: Given the hemodynamic variability and microvascular dysfunction described in AF, the aim of this study was to evaluate the hyperemic response to intracoronary adenosine in AF in comparison with sinus rhythm (SR). METHODS AND RESULTS: This retrospective study included 36 patients in AF and 36 patients in SR. The hyperemic curves were derived in a subset of patients where the required information was available (n = 16 AF, n = 10 SR). AF patients presented a hyperemic response after intracoronary administration of adenosine, which was equivalent to SR in terms of magnitude and time to maximal hyperemia. CONCLUSION: There is equivalent hyperemic response in FFR-guided revascularization in AF versus SR population. Our findings support the use of FFR in evaluating intermediate coronary stenosis in AF.
Subject(s)
Atrial Fibrillation , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Hyperemia , Adenosine/adverse effects , Atrial Fibrillation/diagnosis , Coronary Angiography , Coronary Stenosis/diagnosis , Coronary Vessels , Fibrinolytic Agents , Humans , Hyperemia/chemically induced , Reproducibility of Results , Retrospective Studies , Vasodilator AgentsABSTRACT
Sore throat is one of the most frequent complaints with which patients seek medical help from an otorhinolaryngologist, therapist and pediatrician. OBJECTIVE: To evaluate the efficacy and safety of a combined topical drug with flurbiprofen and cetylpyridinium chloride in patients with sore throat caused by upper respiratory tract infections. MATERIAL AND METHODS: A prospective multicenter open randomized comparative study in parallel groups included 266 adult patients with an established diagnosis of acute pharyngitis or acute tonsillitis aged 18 to 60 years with the main complaint of sore throat caused by viral infections of the upper respiratory tract. The patients included in the study were randomized into two groups of 133 participants each: the 1st group included patients who received the combined agent flurbiprofen 8.75 mg and cetylpyridinium chloride 1.00 mg in the form of tablets for resorption, the 2nd group included patients who received cetylpyridinium chloride 1.2 mg in the form of medicinal lozenges. The effectiveness was evaluated on several scales (RADT, STPIS, TPA, STPR) reflecting subjective and objective indicators of the dynamics of the disease. RESULTS: The studied combination proved to be more effective than the monocomponent agent and was characterized by a more pronounced decrease in sore throat within 2 hours after taking the drug and a decrease in pharyngeal hyperemia. CONCLUSION: According to the results of the study, the use of a drug based on a combination of flurbiprofen and cetylpyridinium chloride was accompanied by a rapid and pronounced decrease in sore throat and pharyngeal hyperemia in patients with upper respiratory tract infections.
Subject(s)
Flurbiprofen , Hyperemia , Pharyngitis , Respiratory Tract Infections , Adult , Cetylpyridinium , Double-Blind Method , Flurbiprofen/adverse effects , Humans , Hyperemia/chemically induced , Hyperemia/complications , Pain , Pharyngitis/diagnosis , Pharyngitis/drug therapy , Pharyngitis/etiology , Prospective Studies , Respiratory Tract Infections/complications , Treatment OutcomeABSTRACT
INTRODUCTION: The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy. METHODS: A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6. RESULTS: The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7 (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (p < 0.001). CONCLUSION: PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively. CLINICAL STUDY NUMBER: European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.
Subject(s)
Glaucoma, Open-Angle , Glaucoma , Hyperemia , Ocular Hypertension , Adult , Antihypertensive Agents/adverse effects , Bimatoprost/therapeutic use , Drug Combinations , Glaucoma/drug therapy , Glaucoma, Open-Angle/drug therapy , Humans , Hyperemia/chemically induced , Hyperemia/drug therapy , Intraocular Pressure , Latanoprost/therapeutic use , Ocular Hypertension/chemically induced , Ocular Hypertension/drug therapy , Prospective Studies , Prostaglandins A/therapeutic use , Prostaglandins F , Timolol/adverse effects , Travoprost/therapeutic useABSTRACT
BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.
Subject(s)
Coronary Stenosis , Fractional Flow Reserve, Myocardial , Hyperemia , Adenosine , Cardiac Catheterization , Coronary Angiography/methods , Coronary Stenosis/diagnosis , Coronary Stenosis/drug therapy , Coronary Vessels , Fractional Flow Reserve, Myocardial/physiology , Humans , Hyperemia/chemically induced , Nicardipine/adverse effects , Severity of Illness Index , Vasodilator AgentsABSTRACT
BACKGROUND: Bimatoprost 0.03% is an intraocular pressure (IOP) lowering prostaglandin analog with different adverse side effects such as potential ocular inflammatory effect and ocular hyperemia. CASE PRESENTATION: We report a case of 80-year-old woman diagnosed with bilateral glaucomatous uveitis, and choroidal detachment in the left eye after topical bimatoprost administration. During the patient's hospitalization, Bimatoprost treatment was discontinued and local steroid therapy was administrated. After 1 week we reported a marked improvement of visual acuity, IOP measurement was 12 mmHg in both eyes. Anterior segment examination showed complete resolution of conjunctival and pericheratic hyperemia with significant reduction of endothelial precipitates in both eyes. CONCLUSIONS: In our case, the anterior granulomatous uveitis occurred in both pseudophakic eyes and the choroidal detachment (CD) in the eye that previously had trabeculectomy. Probably the scar tissue of the trabeculectomy allowed a better penetration of the Bimatoprost or a greater sensitivity due to an altered trabecular tissue. This work confirms that the onset physiopathology mechanism of granulomatous uveitis and CD following instillation of Bimatoprost remains uncertain.
Subject(s)
Choroidal Effusions , Glaucoma , Hyperemia , Uveitis, Anterior , Uveitis , Aged, 80 and over , Amides/adverse effects , Antihypertensive Agents/therapeutic use , Bimatoprost/adverse effects , Cloprostenol/therapeutic use , Female , Glaucoma/chemically induced , Glaucoma/drug therapy , Humans , Hyperemia/chemically induced , Intraocular Pressure , Uveitis/chemically induced , Uveitis/diagnosis , Uveitis/drug therapy , Uveitis, Anterior/drug therapyABSTRACT
Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.
Subject(s)
Arrhythmias, Cardiac/epidemiology , Coronary Stenosis/drug therapy , Fractional Flow Reserve, Myocardial/drug effects , Nicorandil/pharmacology , Papaverine/pharmacology , Tachycardia, Ventricular/prevention & control , Aged , Aged, 80 and over , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , Case-Control Studies , Coronary Angiography/methods , Coronary Angiography/statistics & numerical data , Coronary Stenosis/diagnosis , Coronary Stenosis/physiopathology , Drug Therapy, Combination , Electrocardiography/methods , Female , Fractional Flow Reserve, Myocardial/physiology , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Hyperemia/chemically induced , Hyperemia/physiopathology , Incidence , Long QT Syndrome/chemically induced , Long QT Syndrome/physiopathology , Male , Middle Aged , Nicorandil/administration & dosage , Nicorandil/therapeutic use , Papaverine/administration & dosage , Papaverine/adverse effects , Papaverine/therapeutic use , Retrospective Studies , Safety , Tachycardia, Ventricular/chemically induced , Tachycardia, Ventricular/physiopathology , Treatment Outcome , Vasodilator Agents/administration & dosage , Vasodilator Agents/pharmacology , Vasodilator Agents/therapeutic useABSTRACT
This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines' level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals.
Subject(s)
Diet, Sodium-Restricted/methods , Dietary Approaches To Stop Hypertension/methods , Endothelium, Vascular/drug effects , Microvessels/drug effects , Sodium Chloride, Dietary/administration & dosage , Acetylcholine , Adolescent , Adult , Blood Pressure/drug effects , Dilatation, Pathologic/chemically induced , Female , Healthy Volunteers , Heart Rate/drug effects , Humans , Hyperemia/chemically induced , Male , Microcirculation/drug effects , Nutritional Physiological Phenomena , Sympathetic Nervous System/drug effects , Young AdultABSTRACT
BACKGROUND: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. MATERIALS AND METHODS: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). RESULTS: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. CONCLUSIONS: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.
Subject(s)
Adenosine/pharmacology , Coronary Angiography/methods , Coronary Stenosis , Fractional Flow Reserve, Myocardial/physiology , Hyperemia , Myocardial Ischemia , Aged , Coronary Circulation/drug effects , Coronary Stenosis/diagnosis , Coronary Stenosis/epidemiology , Coronary Stenosis/physiopathology , Correlation of Data , Dose-Response Relationship, Drug , Female , Humans , Hyperemia/chemically induced , Hyperemia/physiopathology , Male , Myocardial Ischemia/diagnosis , Myocardial Ischemia/etiology , Myocardial Ischemia/physiopathology , Predictive Value of Tests , Sensitivity and Specificity , Severity of Illness Index , Spain/epidemiology , Vasodilator Agents/pharmacologyABSTRACT
BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and has aesthetic, physical, and emotional-social sequelae when left untreated. OBJECTIVE: To classify the most common adverse reactions associated with dupilumab treatment in patients with AD. METHODS: The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions associated with dupilumab, topical pimecrolimus, and topical tacrolimus. Phase III clinical trial data were used to compare the rate of herpes infections between the treatment group and placebo group. RESULTS: The most common adverse reaction associated with dupilumab was ocular complications. Herpes infections were extremely rare in the patients with AD being treated with dupilumab. LIMITATIONS: Prescribing information for dupilumab, topical pimecrolimus, and topical tacrolimus is not available. Adverse effects are reported by patients, health care providers, and pharmaceutical companies, they have not been corroborated. CONCLUSIONS: Ocular complications are the most common complication associated with dupilumab. The rate of herpes infection is low in patients being treated with dupilumab, topical pimecrolimus, and topical tacrolimus. There is no significant difference for the rate of herpes infection between, placebo, dupilumab, topical pimecrolimus, and the topical tacrolimus treatment group, suggesting that dupilumab does not affect herpes infection rates.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Dermatitis, Atopic/drug therapy , Eye Diseases/chemically induced , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Blepharitis/chemically induced , Clinical Trials as Topic/statistics & numerical data , Conjunctivitis/chemically induced , Dry Eye Syndromes/chemically induced , Herpesviridae Infections/etiology , Humans , Hyperemia/chemically induced , Interleukin-13/antagonists & inhibitors , Interleukin-4/antagonists & inhibitors , Retrospective Studies , Tacrolimus/adverse effects , Tacrolimus/analogs & derivatives , Tacrolimus/therapeutic use , United States/epidemiology , United States Food and Drug Administration , Virus Activation/drug effectsABSTRACT
Purpose: In this study, we wanted to retrospectively evaluate the effect of the use of topical brimonidine on intraoperative bleeding and surgical hemostasis before strabismus surgery. Methods: Brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops were applied 6 and 3 min before surgery to 44 eyes of 22 patients in group 1 for vasoconstriction. Drops were not applied to 46 eyes of 23 patients in group 2. Preoperative and postoperative photographs and video images were taken. Black-and-white images were used to define the surface areas of the blood vessels. The surface area was calculated by counting the black pixels with ImageJ software. Results: In group 1, redness of eye was observed, on average, at preoperative 339.25 ± 11.52 pixels and intraoperative 247.93 ± 10.63 pixels (P < 0.001). But there was no change in group 2 (preoperative 338.87 ± 8.45 pixels to intraoperative 339.71 ± 9.52 pixels, P > 0.05). The incidence of intraoperative bleeding evaluated by the number of eyes on which cautery was used shows that it was significantly less in group 1 than in group 2 (P < 0.001). Conclusions: The use of topical brimonidine before strabismus surgery facilitates clear monitoring of anatomical structures during surgery by effectively controlling hemorrhage. In the postoperative period, it significantly reduces subconjunctival hemorrhage.