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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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Sympathetic Nerve Activity Efferent Drive and Beta-Blocker Treatment - Effect of Interaction in Systolic Heart Failure.
Joho, S, Akabane, T, Ushijima, R, Hirai, T, Kinugawa, K
Circulation journal : official journal of the Japanese Circulation Society. 2016;(10):2149-54
Abstract
BACKGROUND Although both β-blocker dose (BBD) and sympathetic activity efferent drive are associated with prognosis in chronic heart failure (HF), little is known about the prognostic value of the interaction between them. METHODS AND RESULTS Potential prognostic variables including resting muscle sympathetic nerve activity (MSNA) were investigated in 133 patients with HF (ejection fraction [EF] <0.45). BBD was normalized to therapeutically equivalent doses of carvedilol. Primary cardiovascular endpoints included cardiovascular death and HF hospitalization. Predictors for outcomes were assessed on univariate, multivariate, and Kaplan-Meier analysis. EF was followed for 9 months after MSNA measurement in 102 patients. During the 1,419±824-day follow-up period, 24 patients died (sudden death, n=10; progressive HF, n=14). On multivariate Cox proportional hazard analysis, higher MSNA (P=0.037; HR, 2.01) and lower BBD (<5.0 mg/day; P=0.041; HR, 1.94) were independent predictors of cardiovascular events. Patients were divided into higher MSNA (≥64 bursts/100 beats) and lower MSNA groups. Although lower BBD remained an independent predictor in patients with higher MSNA, BBD was not statistically significant in patients with lower MSNA on univariate analysis. Additionally, there was a lower EF change in patients with lower BBD and higher MSNA. CONCLUSIONS Higher BBD might be necessary to avoid cardiovascular events in HF patients with central sympathetic overactivation. (Circ J 2016; 80: 2149-2154).
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[Journal Club].
Dovjak, P, Püllen, R
Zeitschrift fur Gerontologie und Geriatrie. 2016;(5):455-7
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Effects of different antihypertensive drugs on blood pressure variability in patients with ischemic stroke.
Ji, M, Li, SJ, Hu, WL
European review for medical and pharmacological sciences. 2014;(17):2491-5
Abstract
OBJECTIVE Blood pressure variation is one of the factors that affects the risk of stroke recurrence and prognosis. This study investigates the effects of calcium channel blockers and beta-blockers on blood pressure variability in severe ischemic stroke patients. PATIENTS AND METHODS The clinical data of 24 patients with ischemic stroke in our intensive care unit were analyzed, and received amlodipine or metoprolol for more than 14 days with 24-hour ambulatory blood pressure monitoring. All patients aged 61-90 years, with GCS score ≤ 8 or associated with other organ dysfunction. RESULTS Among these 24 ischemic stroke patients, 12 received amlodipine and 12 received metoprolol. The observation period was divided into two phases: 1-6 days and 7-14 days. The decrease in blood pressure was faster in the metoprolol group than in the amlodipine group, while the average standard deviation was significantly greater and the smoothness index was less. CONCLUSIONS Metoprolol has faster onset than amlodipine and less blood pressure variability than metoprolol.
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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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Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs.
Miwa, Y, Ikeda, T, Mera, H, Miyakoshi, M, Hoshida, K, Yanagisawa, R, Ishiguro, H, Tsukada, T, Abe, A, Yusu, S, et al
Circulation journal : official journal of the Japanese Circulation Society. 2010;(5):856-63
Abstract
BACKGROUND Occasionally it is difficult to inhibit electrical storm (ES) with standard pharmacological treatment. In the present study the effect of landiolol, an ultra-short-acting beta(1)-selective blocker, on ES refractory to class III antiarrhythmic drugs was evaluated. METHODS AND RESULTS The study group comprised 42 consecutive patients who developed ES for which intravenous class III antiarrhythmic drugs, such as amiodarone and nifekalant, were ineffective. Landiolol was administered intravenously with an initial dose of 2.5 microg x kg(-1) x min(-1), which was doubled if it was ineffective, up to a maximum dose of 80 microg x kg(-1) x min(-1). Landiolol inhibited ES in 33 patients (79%) at a mean dose of 7.5+/-12.2 microg x kg(-1) x min(-1). All patients in whom landiolol was ineffective died of arrhythmia. Of the 33 patients in whom landiolol was effective, 25 survived and were discharged (60% of all patients). Landiolol significantly decreased heart rate (P<0.0001), but did not affect blood pressure. Landiolol was not discontinued for adverse effects in any of the responders. Age, APACHE II score, and pH of arterial blood gas differed significantly between the responders and nonresponders. CONCLUSIONS Landiolol is useful as a life-saving drug for class III antiarrhythmic drug-resistant ES. The main mechanism of ES refractory to class III antiarrhythmic drugs could be abnormal automaticity but not reentry.
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Quality of life and efficacy of nebivolol in an open-label study in hypertensive patients. the QoLaN study.
Hermans, MP, De Coster, O, Seidel, L, Albert, A, Van de Borne, P
Blood pressure. Supplement. 2009;:5-14
Abstract
BACKGROUND Nebivolol is a highly selective beta-adrenoreceptor antagonist with vasodilating properties. This study investigated its effect on quality of life (QoL) and blood pressure (BP) in real life conditions. In total, 1468 patients were enrolled, 12% diabetics. Nebivolol was prescribed as monotherapy, add-on or switch medication. METHODS In this open-label, prospective study, the JNC-VII BP target values were used: < 140/90 and < 130/80 mmHg for diabetics. The responder rate and the QoL was determined at baseline and after 4 and 8 weeks. RESULTS After 4 weeks, 27% of subjects reached target BP, 45% after 8 weeks. The responder rates were 92, 90 and 83% for the monotherapy, add-on and switch groups. Compared with baseline, all showed statistical significance at 8 weeks. Similarly to results for the QoL after 8 weeks, the mean improvement in QoL for all three groups was 9-10 points (total range: 0-88). CONCLUSIONS The study demonstrates that nebivolol in mild to moderate hypertension is associated with overall improvements in QoL, with a marked BP-lowering effect, in monotherapy, add-on or switch, irrespective of the glucose tolerance status. It may be hypothesized that its dual mode of action explains its BP-lowering effect as well as the tolerability.
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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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[The importance of bisoprolol in prevention of heart left ventricular hypertrophy in patients with long term L-thyroxin suppressive therapy, after the operation of differentiated thyroid carcinoma].
Matuszewska, G, Marek, B, Kajdaniuk, D, Przywara-Chowaniec, B, Jarzab, J, Jarzab, B
Endokrynologia Polska. 2007;(5):384-96
Abstract
INTRODUCTION Patients with differentiated thyroid carcinoma have to undergo radical surgical treatment, which includes total thyreoidectomy, radioiodine therapy and a life-time suppressive therapy with L-thyroxine. The aim of this study was a prospective evaluation of left ventricular hypertrophy during L suppressive-thyroxine treatment in patients treated for differentiated thyroid carcinoma. MATERIAL AND METHODS The examined group comprised 50 patients with differentiated thyroid carcinoma, treated by total thyroidectomy and 131I therapy. Echocardiographic measurements were needed for estimation of left ventricular mass and its index, according to recommendations of American Echocardiography Society. RESULTS During two-years long suppressive therapy we observed a significant rise in left ventricular mass. In woman group left ventricular mass was increased from 168+/-39 g to 204+/-45 g (p<0.001) and in men from 205+/-60 to 320+/-21 g. Likewise, left ventricular mass index was increased in women group from 96+/-18 g/m(2) to 116+/-25 g/m(2) (p<0.001) and in men group from 107+/-37 g/m(2) to 158+/-28 g/m(2). Simultaneous treatment with bisoprolol caused a regression of left myocardial hypertrophy. Already after 6 months of simultaneous treatment with L-thyroxin and bisoprolol, for left ventricular mass was reduced to normal: in woman 165+/-35 g, and in men to 178+/-38 g. Analogous results were obtained left ventricular mass index. After 6 months it was reduced to 94+/-12 g/m(2) in woman and in men to 132+/-32 g/m(2). CONCLUSIONS 1. In differentiated thyroid cancer patients, treated postoperatively with L-thyroxine suppressive therapy, left ventricular hypertrophy is observed already during the first year of suppressive therapy and progresses during the next year of treatment. 2 Addition of a beta-adrenergic antagonist to suppressive doses of L-thyroxine causes a regression of left ventricular hypertrophy, thus, beta-adrenergic antagonists should be administered in this group of patients.