Infantil Hemangioma and Optimum Dose of Propranolol Treatment: A Retrospective Tertiary-Center Study

Background/Objectives: Propranolol is the mainstay treatment of infantile hemangioma, and the optimal dose is unclear. Few studies are comparing the efficacy of propranolol dose of 2 vs.3 mg/kg/day. We compared the efficacy between these two doses and propranolol groups with no treatment group. Methods: One hundred eight patients with infantile hemangioma (15 days-27 months of age) were examined. The patients with high-risk features and/or a score of >6 points are given propranolol with a final dose of 2 or 3 mg/kg/day according to tolerance for 6-12 months. The resolutions rates for propranolol vs. placebo and propranolol 2 mg/kg/day vs. 3 mg/kg/day are compared. Results: The demographic and clinical features of the groups ( the non-treatment, propranolol 2 mg/kg/day group, propranolol 3 mg/kg/day group) are similar. Propranolol is significantly efficent in infantil hemangioma treatment (p<0.001). The resolution rates are not statistically different between 2 mg/kg/day propranolol group vs 3 mg/kg/day propranolol group at the sixth (68,59 ± 28,95 vs 73,44 ± 32,54)(p=0,673) and twelfth month (p=0,673) (89,08 ± 46,58 vs 91,13 ± 37,46 respectively )of follow up. A milld (n=3)(4%) adverse event was reported with no need for cessation.Conclusions: Propranolol is a safe drug for treating infantile hemangioma with an ideal dose of 2 mg/kg/day rather than 3 mg/kg/day.

Neural substrates of propranolol-induced impairments in the reconsolidation of nicotine-associated memories in smokers

The majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

Carvedilol Versus Propranolol in the Prevention of Variceal Rebleeding in Hepatic Schistosomiasis: Efficacy and Safety

Background: The betablockers combined with endoscopic variceal band ligation (EVL) is the most effective prevention of variceal rebleeding. The aim of this study is to evaluate the efficacy and safety of carvedilol compared to propranolol as secondary prevention of variceal bleeding in hepatic schistosomiasis. Methods: All patients with portal hypertension due to schistosomiasis presenting for EVL with at least one episode of variceal bleeding were included and randomized into propranolol + EVL and Carvedilol + EVL groups. Results: Sixty-one patients were selected and randomized into the propranolol group (n=30) and carvedilol group (n=31). We noted less recurrence of bleeding in the carvedilol group (n=1) than in the propranolol group (n=3) (3.33% vs 10%; p=0.30). Bleeding recurrence occurred after 30 days in the carvedilol group and after 5, 45 and 90 days in the propranolol group. At 4 months, a significant reduction in mean arterial pressure (-4.13 mmHg; 95%CI: -6.27 and -1.99; p <0.05) and heart rate (-12.13 mmHg; 95%CI: -13.92 and -10.35; p<0.05) was found in the carvedilol group. There was no significant difference between the two groups on the mean difference in mean arterial pressure. A patient in the carvedilol group presented breathing difficulty. No adverse effects have been demonstrated in the propranolol group. Conclusion: Carvedilol is as effective as propranolol in the prevention of variceal rebleeding in hepatic schistosomiasis.

Comparing efficacy and safety of sodium valproate with propranolol in paediatric migraine prophylaxis

Migraine is a common disorder of the paediatric age group. Propranolol has been used in prophylaxis for migraine. The use of Sodium valproate in the prophylaxis of migraine is not known. It is postulated that it increases the level of GABA in the brain that will decrease events related to migraine in the cortex. All parents of the patient were advised to keep diaries for noting time, date, severity and duration of headache during the study period, which was for a period of 6 wks. The decreased frequency of headache more than in Group A was 68% and propranolol group was 68.89%. In group A(sodium valproate), patients showed a reduction in headache duration and 52% in Group B. 20% of them headache free in Group A and 18% in Group B. Decrease in the severity of headache in Group A was 52% while 50% in Group B. The mean headache frequency before and after treatment was reduced from 8 to 2.5 attacks per month in group A and from 8.2 to 2.6 in group B. The t-value is 11 for group A. Sodium valproate is more effective and safer in migraine prophylaxis as compared with propranolol.

Blood Pressure Correlates Asymmetrically with Neuropeptidase Activities of the Left and Right Frontal Cortices

It was suggested that the brain-heart connection is asymmetrically organized. However, evidence connecting neurochemical factors from each brain hemisphere with changes in cardio-vascular functions have not yet been reported. In order to analyze potential asymmetrical connections between brain neurochemical factors with cardio-vascular functions, we studied the level of correlations between the left and right frontal cortex (FC) soluble (Sol) and membrane-bound (MB) neuropeptide-degrading enzymes alanyl (AlaAP), cystinyl (CysAP), and glutamyl (GluAP) aminopeptidase activities, involved among others in the metabolism of angiotensins, with heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure, in rats treated or not with hypotensive or hypertensive drugs such as captopril, propranolol or L-NAME. The present study suggests the existence of a bidirectional asymmetrical connection between these brain neuropeptidases and cardio-vascular functions. Specifically, depending on treatment, in control group, Sol AlaAP from the left FC correlates negatively with SBP and DBP. In captopril-treated animals, MB CysAP and MB GluAP from the right FC correlate negatively with HR. In L-NAME treated rats, Sol CysAP from the right FC correlates negatively with DBP. No significant correlations were observed in the propranolol group. Considering together all the values obtained from the left or the right cortex of the four groups regardless of drug treatment, the results demonstrated significant negative correlations between these neuropeptidase activities, mainly from the left frontal cortex, with the levels of systolic and diastolic blood pressure. Remarkably, these findings contrast drastically with previously reported results indicating significant positive correlations between the left frontal cortex with other peripheral functions such as water intake and diuresis. Both results represent noteworthy information that strongly supports the concept of a bidirectional asymmetric organization of neurovisceral integration involving left and right brain neurochemical processes with peripheral physiological functions, most probably mediated by the autonomic nervous system. Overall, the present results suggest that cognitive functions involving the frontal cortex may be asymmetrically connected with peripheral physiological processes, and vice versa.

Sodium Valproate versus Propranolol in Chronic Migraine Prophylaxis

Background: There is a need for effective, well tolerated and affordable drug for chronic migraine prophylaxis in low socioeconomic countries. Objective: To study the efficacy and safety of propranolol and sodium valproate (a food and drug administration approved and widely used treatment for prevention of migraine) as a prophylactic treatment in chronic migraine (CM) patients and to compare their efficacy and safety to each other. Methods: In this single center, open labeled clinical trial, 40 patients with CM were subdivided into two group: group 1 (n=20) treated with propranolol and group 2 (n=20) treated with sodium valproate. Patients maintained headache diaries over a 1-month baseline period and a 6- month active study period. The evaluation of the treatment was done after 3 and 6 months of the initiation of the treatment. The efficacy measures were evaluation of monthly attacks frequency and attacks severity using VAS of pain (visual analogue scale. Disability and impact of migraine were evaluated using Migraine assessment disability scale (MIDAS) and Headache Impact Test (HIT-6). Throughout the study, patients were monitored for any symptoms or signs of adverse effects. Results: Of 40 patients participated in this study (mean age, 33.48; females 72.5%). At the 6th month, the study was completed by 27 patients (propranolol; n=14 and sodium valproate; n=13). Between 55 and 62% of both groups reported more than 50% reduction in monthly attacks frequency. In both groups, there was significant reduction of VAS of pain scores. Both groups showed significant improvement of HIT-6 and MIDAS scores. Before the start of treatment, 85% to 100% of patients in both groups had severe MIDAS and HIT-6 scores. At the end of the study, only 35.7% of propranolol group and 30.8 of sodium valproate group showed severe MIDAS scores and 50% of propranolol group and 40% of sodium valproate group reported severe HIT-6 scores. 55% (n=11) of patients in propranolol reported AEs related to treatment compared to 75% (n=15) in the sodium valproate group. A higher proportion of patients discontinued the treatment because of AEs in Na valproate group compared to sodium valproate group with no statistically significant difference in between (20% vs. 5%, respectively). Conclusions: Propranolol and sodium valproate demonstrated similar efficacy and tolerability in the prophylactic treatment of CM.

Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (−2.03 ± 1.7 as compared with −0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (−1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

Evaluation of the Oral Propranolol Effect on Retinopathy of Prematurity: Randomized Clinical Trial

Background: Despite rapid advances in neonatal care in both industrialized and developing countries, retinopathy of prematurity (ROP) still remains the main reason of infants' blindness and visual impairment. There is some evidence that Beta-adrenergic system may be involved in infants' ROP. Considering that few studies have been done on effects of oral propranolol on prevention retinopathy pre maturity in premature infants, we designed this clinical trial to investigate the effects of oral propranolol on infants. Methods: This study is a clinical trial in which 27 premature infants with gestational age greater than 27 weeks and afflicted with retinopathy pre maturity grade 1 and 2 hospitalized at Shahid Sadoughi hospital of Yazd city.They were randomized to receive 0.5 mg/kg/12hours oral propranolol or control. Premature infants were controlled and hospitalized at NICU and their BP, heart rate and Hyperemesis gravidarum (H.G) were monitored. Results: Twenty-four newborns were included, 12 in the control group and 12 in the propranolol group and 3 of infants were excluded from the study (2 of propranolol group and 1 of control group) 81.34 percent of treatment group were recovered and healed compared to 66.7 percent of control group which not significantly difference. Conclusion: Some studies about Beta Blockers' recessive effect on ROP have been done which in most recovery was the result but some serious side effects were also reported. In this study there was no positive effect on recovery of ROP but the percent of recovery was slightly higher in propranolol group compared to control group. Fortunately there were no reports of side effects this time due to usage of lower dose propranolol.Recent studies state that propranolol cannot be used as a good alternative to other treatments but it can prevent the disease from getting worse. We can also reduce its side effects by changing the dosage.

Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis

Alcoholic cirrhosis (AC) leads to enormous disease burden and occupies a substantial proportion in the etiology of hepatocellular carcinoma (HCC), but scarce attention has been paid to this topic. Besides, propranolol has been reported to decrease the rate of HCC in viral hepatitis. We conducted a retrospective tertiary-center cohort study to identify the HCC incidence in AC patients with or without propranolol. A total of 1,046 AC patients with hospitalization had been screened, and those with regular follow-up for three years or otherwise until the date of malignancy diagnosis without meeting exclusion criteria were enrolled; finally, 23 AC patients with propranolol and 46 AC patients without propranolol were analyzed after twofold propensity-score matching. The cumulative incidence of HCC was lower in the propranolol group (log-rank test, P=0.046). Furthermore, we undertook the meta-analysis of annual incidence of HCC in AC patients, and 1,949 publications were screened, within which eight studies were analyzed; the pooled annual incidence was 2.41%, which was higher than the calculated annual incidence of HCC in our AC cohort with propranolol (1.45%). In conclusion, propranolol is associated with decreased risk of HCC incidence in patients with AC.