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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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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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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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Metoprolol prevents sodium retention induced by lower body negative pressure in healthy men.
Wuerzner, G, Chiolero, A, Maillard, M, Nussberger, J, Burnier, M
Kidney international. 2005;(2):688-94
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BACKGROUND Lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal systems, and a renal tubular and hemodynamic response that mimics the renal adaptation observed in congestive heart failure (CHF). As beta-blockers play an important role in the management of CHF patients, the effects of metoprolol on the renal response were examined in healthy subjects during sustained LBNP. METHODS Twenty healthy male subjects were randomized in this double blind, placebo versus metoprolol 200 mg once daily, study. After 10 days of treatment, each subject was exposed to 3 levels of LBNP (0, -10, and -20 mbar) for 1 hour, each level of LBNP being separated by 2 days. Neurohormonal profiles, systemic and renal hemodynamics, as well as renal sodium handling were measured before, during, and after LBNP. RESULTS Blood pressure and heart rate were significantly lower in the metoprolol group throughout the study (P < 0.01). GFR and RPF were similar in both groups at baseline, and no change in renal hemodynamic values was detected at any level of LBNP. However, a reduction in sodium excretion was observed in the placebo group at -20 mbar, whereas no change was detected in the metoprolol group. An increase in plasma renin activity was also observed at -20 mbar in the placebo group that was not observed with metoprolol. CONCLUSION The beta-blocker metoprolol prevents the sodium retention induced by lower body negative pressure in healthy subjects despite a lower blood pressure. The prevention of sodium retention may be due to a blunting of the neurohormonal response. These effects of metoprolol on the renal response to LBNP may in part explain the beneficial effects of this agent in heart failure patients.
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Recruitment of African Americans with chronic renal insufficiency into a multicenter clinical trial: the african american study of kidney disease and hypertension.
Phillips, RA, Faulkner, M, Gassman, J, Jaen, L, Kusek, JW, Norris, K, Ojo, A
Journal of clinical hypertension (Greenwich, Conn.). 2004;(8):430-6
Abstract
In patients with hypertensive nephrosclerosis, the African American Study of Kidney Disease and Hypertension (AASK) demonstrated the superiority of angiotensin-converting enzyme inhibitor therapy in blunting progression of renal disease compared with a b blocker and a dihydropyridine calcium channel blocker. In addition, the study found that a blood pressure treatment strategy that resulted in an achieved blood pressure of 128/78 mm Hg (low blood pressure goal) was no more effective in slowing the progression of renal disease than a strategy that resulted in a blood pressure of 141/85 mm Hg (usual blood pressure goal). AASK, which enrolled only African Americans with mild to moderate chronic renal insufficiency, also provided an opportunity to evaluate recruitment methods in minority populations. Eighty-three percent of patients were recruited through screening in clinical practice. To randomize 635 patients, 558,295 charts were reviewed (approximately 879 charts per randomized patient). More than half of the randomized patients (n=635 or 58%) were found by chart review. Sixty percent of women with creatinine levels considered within the normal range had at least mild chronic renal insufficiency. Screening in clinical practice was the most effective strategy to recruit participants with mild to moderate chronic renal insufficiency and hypertension into the clinical trial. This technique may also be an effective approach in trials of other essentially asymptomatic conditions.
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Effect of beta-blockers on peripheral skin microcirculation in hypertension and peripheral vascular disease.
Ubbink, DT, Verhaar, EE, Lie, HK, Legemate, DA
Journal of vascular surgery. 2003;(3):535-40
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Abstract
OBJECTIVE This study was undertaken to investigate the possible negative effect of beta-blockers on skin microcirculation in patients with intermittent claudication and hypertension. Methods and materials In this clinical crossover study, 20 patients with mild to moderate hypertension, treated with long-term beta-blockade, and intermittent claudication or ischemic rest pain, underwent assessment of peripheral circulation before and after 2-week withdrawal of beta-blocking therapy and again 2 weeks after restarting therapy. Replacement therapy (calcium antagonist) was given if considered necessary to control hypertension. Skin microcirculation was assessed with three noninvasive techniques: capillary microscopy of the hallux nailfold, transcutaneous oximetry of the forefoot, and laser Doppler fluxmetry of the great toe. RESULTS Mean initial blood pressure was 163/81 mm Hg. Mean heart rate significantly increased with withdrawal of beta-blocker, from 65 bpm to 85 bpm. No significant differences in skin microcirculation and blood pressure were found between measurements obtained before, during, and after withdrawal of beta-blocking therapy. Patients experienced no change in symptoms during the study. CONCLUSION beta-Blockers do not appear to have a negative effect on peripheral skin microcirculation and are therefore not contraindicated to treat hypertension when intermittent claudication or ischemic rest pain is also present.
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LIFE and ARBITER.
Liebson, PR
Preventive cardiology. 2003;(2):108-11
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Use of thallium-201 myocardial scintigraphy for the prediction of the response to beta-blocker therapy in patients with dilated cardiomyopathy.
Hara, Y, Hamada, M, Ohtsuka, T, Ogimoto, A, Saeki, H, Suzuki, J, Matsunaka, T, Nakata, S, Shigematsu, Y
Circulation journal : official journal of the Japanese Circulation Society. 2002;(12):1139-43
Abstract
This study was performed to evaluate whether thallium-201 myocardial scintigraphy (Tl-201) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predict the usefulness of beta-blocker therapy in patients with dilated cardiomyopathy (DCM). Tl-201 and MIBG were performed in 47 patients before beta-blocker therapy. Patients were classified into group A, if their cardiac function improved, and group B, whose function remained unchanged. Two types of extent score (ES) by Tl-201 were proposed to quantitate myocardial damage, mean-2SD (ES-2) and mean-3SD (ES-3). The ES difference between ES-2 and ES-3 was calculated, and according to ES and ES difference, DCM cases were classified into 3 groups: mild-defect type (mild-type), moderate-defect type (moderate-type) and severe-defect type (severe-type). The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated, and the percent washout ratio of myocardial MIBG was obtained from these data. Group A comprised 18 mild-type, 14 moderate-type and 1 severe-type cases, and group B comprised 5 mild-type, 4 moderate-type and 5 severe-type cases. A significant relation was observed between the defect type on Tl-201 and the response to beta-blocker therapy (p=0.0090). Both H/M MIBG uptake ratios and washout ratio were not significantly different in the 2 groups. Tl-201 may be useful for predicting the response to beta-blocker therapy in patients with DCM.