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Association of Weight-Adjusted Caffeine and β-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery.
Roizenblatt, M, Dias Gomes Barrios Marin, V, Grupenmacher, AT, Muralha, F, Faber, J, Jiramongkolchai, K, Gehlbach, PL, Farah, ME, Belfort, R, Maia, M
JAMA ophthalmology. 2020;(8):819-825
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Abstract
IMPORTANCE Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance. OBJECTIVES To establish weight-adjusted cutoffs for caffeine and β-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons. DESIGN, SETTINGS, AND PARTICIPANTS This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg). INTERVENTIONS Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days. MAIN OUTCOMES AND MEASURES An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons. RESULTS Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, -53.0; 95% CI, -99.3 to -6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, -12.0; 95% CI, -21.2 to -2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03). CONCLUSIONS AND RELEVANCE The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.
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Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.
Filippi, L, Cavallaro, G, Berti, E, Padrini, L, Araimo, G, Regiroli, G, Bozzetti, V, De Angelis, C, Tagliabue, P, Tomasini, B, et al
BMC pediatrics. 2017;(1):165
Abstract
BACKGROUND Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.
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Efficacy and safety of cinnarizine in the prophylaxis of migraine headaches in children: an open, randomized comparative trial with propranolol.
Togha, M, Malamiri, RA, Rashidi-Ranjbar, N, Asa, S, Mahvelati, F, Ashrafi, MR
Acta neurologica Belgica. 2012;(1):51-5
Abstract
Migraine headaches are common in children. Early diagnosis and appropriate interventions are mandatory to prevent decades of suffering and diminished quality of life. There is need for data regarding the efficacy and safety of prophylactic agents in children with migraine; therefore, we designed a randomized clinical trial to compare the efficacy and safety of cinnarizine with that of a well-known prophylactic agent (propranolol) in the prophylaxis of pediatric migraine headache. A total of 120 patients aged between 6 and 17 years were recruited and 113 patients succeeded in completing all phases of the trial. Of them, 57 patients were given cinnarizine, and propranolol was administered in 56 patients. Reduction in headache frequency was the main response to treatment. Cinnarizine reduced the baseline headache frequency by more than 50% in 74.6% of patients and the mean headache frequency per month was reduced from 11.851 ± 0.739 (mean ± SEM) to 3.358 ± 0.739 (mean ± SEM) attacks per month (P < 0.001). In the propranolol group, more than 50% reduction of the baseline headache frequency was seen in 72.5% of patients and the mean headache frequency per month was reduced from 10.264 ± 0.830 (mean ± SEM) to 2.774 ± 0.830 (mean ± SEM) attacks per month (P < 0.001). No significant difference was seen in 50% reduction of the baseline headache frequency between treatment groups (P = 0.358). No significant adverse effects were reported. In this open study, cinnarizine appeared thus as effective as propranolol and safe for the prophylaxis of migraine in children, but this remains to be confirmed in a double-blind placebo-controlled trial.
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Treatment with propranolol of 6 patients with idiopathic aquagenic pruritus.
Nosbaum, A, Pecquet, C, Bayrou, O, Amsler, E, Nicolas, JF, Bérard, F, Francès, C
The Journal of allergy and clinical immunology. 2011;(5):1113
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Variation in almotriptan effectiveness according to different prophylactic treatments.
Bermejo, PE, Dorado, R, Gomez-Arguelles, JM
Headache. 2009;(9):1277-82
Abstract
OBJECTIVE To evaluate the effect of different migraine prophylaxis medications on subject responsiveness to almotriptan. BACKGROUND There is evidence supporting an increase of responsiveness of symptomatic medications for migraine attacks by some prophylactic treatments although this has not been probed. METHODS A total of 345 patients (230 women, mean age 37.3) with episodic or chronic migraine were classified according to the prophylaxis they were taking in the following groups: (1) no prophylactic medication; (2) propranolol; (3) topiramate; (4) flunarizine. Decrease in Analogical Visual Scale and pain-free at 2 hours after almotriptan intake was assessed at 2 months. Side effects and discontinuation or treatment were also assessed. RESULTS Headache severity was reduced 4.2 in control group, 5.3 in propranolol group, 4.1 in topiramate group, and 4.0 in flunarizine group, whereas pain-free status was achieved in 37.3%, 48.7%, 36.1%, and 38.1% respectively. These two parameters were statistically significative between propranolol and control groups. Side effects were similar in all groups. CONCLUSIONS Our results displayed a higher efficacy of almotriptan in propranolol group and we hypothesized it may be due to a common mechanism of action at serotoninergic receptors.
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Visfatin plasma concentrations in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function.
Ozkaya, M, Sahin, M, Cakal, E, Yuzbasioglu, F, Sezer, K, Kilinc, M, Imrek, SS
Journal of endocrinological investigation. 2009;(5):435-9
Abstract
Alterations in thyroid function are associated with changes in body weight, metabolism, and low-grade inflammation. In several studies, plasma levels of visfatin were found to be associated with body mass index, diabetes, and metabolic syndrome. In our study we aimed to evaluate visfatin levels according to thyroid dysfunction. The study cohort comprised 56 Hashimoto thyroiditis patients with hypothyroidism (43.94+/-14.27 yr), 56 Graves patients with hyperthyroidism (45.87+/-13.28 yr), and 56 euthyroid healthy subjects (45.23+/-7.11 yr) as a control group. In addition, we evaluated the effect of therapy on plasma visfatin levels in 16 hypothyroid and in 25 hyperthyroid patients. Markedly low visfatin levels were found in hyperthyroid patients [9.44 (8.07- 10.8) ng/ml] compared with the hypothyroid [49.93 (40.72- 59.1) ng/ml] and control groups [38.6 (30.6-46.6) ng/ml] (p<0.001, p<0.001). Plasma visfatin levels in patients with hypothyroidism decreased significantly following treatment [58.58 (10.21-190.7) ng/ml vs 40.00 (10.01-102.6) ng/ml; p=0.001]. Plasma visfatin levels increased significantly after antithyroid therapy in patients with hyperthyroidism [7.86 (1.02-19.23) ng/ml vs 12.63 (3.48-110.9) ng/ml; p<0.001]. There were negative correlations between visfatin levels with free T3 (r=-0.719, p<0.001), and free T4 (r=-0.716, p<0.001) levels. There was a positive correlation between visfatin and TSH levels (r=0.701, p<0.001). There was a negative correlation between delta visfatin levels with delta free T3, delta free T4 (r=-0.686, p<0.001; r=-0.624, p<0.001). Visfatin thus seems to be regulated by thyroid hormones. While the influence of thyroid dysfunction on adipocytokine production and release is still poorly understood, the results of our study suggest that the effects of hyper- and hypothyroidism on various metabolic parameters may be partly mediated by visfatin.
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Mental stress impairs endothelial vasodilatory function by a beta-adrenergic mechanism.
Eriksson, M, Johansson, K, Sarabi, M, Lind, L
Endothelium : journal of endothelial cell research. 2007;(3):151-6
Abstract
Mental stress has been shown to impair endothelium-dependent vasodilation (EDV) in the human forearm. The aim of this study was to investigate if this response could be blunted by local infusions of beta-blockade (propranolol), alpha-blockade (phentolamine), or neurogenic blockade. Thirty-one young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of metacholine (MCh; inducing EDV) and sodium nitroprussid (SNP; inducing endothelial-independent vasodilation [EIDV]), respectively. These measurements were repeated during a 5-min mental arithmetic stress test without (n = 8) or with concomitant local infusion of propranolol (n = 7) or phentolamine (n = 8) in the forearm or during axillary plexus blockade (n = 8). An index of endothelial vasodilatory function (EFI) was calculated as the EDV to EIDV ratio. Mental stress impaired EDV significantly (p < .05), and as a result, EFI was significantly reduced (p = .02). This effect on EFI could be blocked by propranolol and neurogenic blockade but not by phentolamine (p < .05). Thus, impairment of endothelial vasodilatory function induced by mental stress could be blocked by beta-adrenergic, but not alpha-adrenergic, receptor blockade.
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Effects of hydrochlorothiazide and propranolol treatment on chylomicron metabolism in hypertensive objects.
Bernik, MM, Heimann, JC, Nakandakare, ER, Cazita, PM, Nunes, VS, Rocha, JC, Neves, MQ, Quintão, EC
Canadian journal of physiology and pharmacology. 2005;(7):617-23
Abstract
Modifications in chylomicron metabolism caused by antihypertensive drugs were investigated in hypertensive subjects because previous studies had indicated that diuretics and beta-blockers modify the plasma lipid concentrations through mechanisms that were not fully understood. A triglyceride-rich emulsion resembling lymph chylomicrons, labeled with (3H) triolein and (14C) cholesteryl oleate, was infused intravenously into mildly hypertensive patients after 8 weeks on placebo and subsequently on hydrochlorothiazide (n = 10) or propranolol (n = 8). The residence time of both radioactivities in plasma was utilized for the simultaneous calculation of the particle remnant removal rate and of the lipoprotein lipase activity expressed as a delipidation index = 1 - [(3H) triolein residence time/(14C) cholesteryl oleate residence time]. Treatment with hydrochlorothiazide diminished the delipidation rate value whereas propranolol mildly increased the removal rate of the remnant particle. These alterations of the chylomicron kinetics were not accompanied by changes in plasma triglycerides, glucose, and insulin concentration as measured in the fasting state. The impairment of the lipoprotein lipase activity by thiazides and the faster removal rate of the whole particle by propranolol could explain the reason why in previous clinical studies the simultaneous use of these drugs does not aggravate the hyperlipidemia known to be induced by thiazides alone.
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The effect of propranolol on glyceryltrinitrate-induced headache and arterial response.
Tvedskov, JF, Thomsen, LL, Thomsen, LL, Iversen, HK, Williams, P, Gibson, A, Jenkins, K, Peck, R, Olesen, J
Cephalalgia : an international journal of headache. 2004;(12):1076-87
Abstract
Prophylactic drug trials in migraine are long-lasting and expensive and require long-term toxicology information. A human migraine model would therefore be helpful in testing new drugs. Immediate headache and delayed migraine after glyceryltrinitrate (GTN) has been well characterized. We have recently shown that sodium valproate has prophylactic effect in the GTN model. Here we report our experience with propranolol in this model. Nineteen subjects with migraine without aura and 16 sex- and aged-matched healthy subjects were included in a two-centre randomized double-blind cross-over study. Fourteen migraine subjects and 14 healthy subjects completed the study and results from comparison of the 28 subjects are reported. Randomly propranolol 160 mg or placebo were each given daily for 14 days to both migraine and healthy subjects. A 20-min intravenous infusion of GTN 0.25 microg/kg per min was administered on a study day at the end of both pretreatment periods. Headache was registered for 12 h after GTN infusions. Its intensity was scored on a numerical verbal rating scale from 0 to 10. Fulfilment of International Headache Society (HIS) criteria was recorded for 24 h. Radial and superficial temporal artery diameters and blood velocity of both middle cerebral arteries were measured. All migraine subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 5, range 0-7) compared with placebo (median 5, range 0-10) (P = 0.441). Eight of the 14 completing migraine subject developed IHS 1.1 migraine after GTN, two subjects on both days, three subjects only after placebo, and three subjects only after propranolol. No reduction of GTN-induced migraine was found after propranolol compared with placebo (5 vs. 5, P = 1.000). All healthy subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 2, range 1-5) compared with placebo (median 1, range 1-7) (P = 0.315). Two subjects fulfilled IHS criteria 1.1 for migraine without aura after propranolol but not after placebo. The fulfilment was short lasting and did not require rescue medication. Headache after GTN was more pronounced in migraine subjects than in healthy subjects both with (P = 0.003) and without pretreatment with propranolol (P = 0.017). We found that 2 weeks of propranolol constricted the radial artery in healthy subjects but not in migraine subjects. GTN-induced vasodilatation abolished this difference. Mean maximum blood flow velocity in the middle cerebral artery was higher in healthy subjects than in migraine patients (P = 0.003-0.033) and unaffected by propranolol. We observed no effect of propranolol on GTN-induced headache and migraine. This could indicate that GTN induces migraine at a deeper level of the pathophysiological cascade of migraine than the prophylactic effect of propranolol. Propranolol does not constrict cerebral arteries, which therefore cannot be part of its mechanism of action in migraine.
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Distal myocardial protection during percutaneous coronary intervention with an intracoronary beta-blocker.
Wang, FW, Osman, A, Otero, J, Stouffer, GA, Waxman, S, Afzal, A, Anzuini, A, Uretsky, BF
Circulation. 2003;(23):2914-9
Abstract
BACKGROUND Experimental studies have demonstrated that intravenous beta-blocker administration before coronary artery occlusion significantly reduces myocardial injury. Clinical studies have shown that intracoronary (IC) propranolol administration before percutaneous coronary intervention (PCI) delays myocardial ischemia. The present study tested the hypothesis that IC propranolol treatment protects ischemic myocardium from myocardial damage and reduces the incidence of myocardial infarction (MI) and short-term adverse outcomes after PCI. METHODS AND RESULTS Patients undergoing PCI (n=150) were randomly assigned in a double-blind fashion to receive IC propranolol (n=75) or placebo (n=75). Study drug was delivered before first balloon inflation via an intracoronary catheter with the tip distal to the coronary lesion. Biochemical markers were evaluated through the first 24 hours and clinical outcomes to 30 days. Evidence of MI with creatine kinase-MB elevation after PCI was seen in 36% of placebo and 17% of propranolol patients (P=0.01). Troponin T elevation was seen in 33% of placebo and 13% of propranolol patients (P=0.005). At 30 days, the composite end point of death, postprocedural MI, non-Q-wave MI after PCI hospitalization, or urgent target-lesion revascularization occurred in 40% of placebo versus 18% of propranolol patients (hazard ratio 2.14, 95% CI 1.24 to 3.71, P=0.004). CONCLUSIONS IC administration of propranolol protects the myocardium during PCI, significantly reducing the incidence of MI and improving short-term clinical outcomes.