-
Plastic and Reconstructive Surgery Apr 2021Propranolol, a nonselective β-adrenergic receptor antagonist, is approved by the U.S. Food and Drug Administration to treat problematic infantile hemangiomas, but a...
BACKGROUND
Propranolol, a nonselective β-adrenergic receptor antagonist, is approved by the U.S. Food and Drug Administration to treat problematic infantile hemangiomas, but a subset of patients experience treatment complications. Parents wary of long-term use and side effects consult plastic surgeons on surgical options or as a second opinion. Understanding the mechanism(s) of action of propranolol will allow plastic surgeons to better inform parents.
METHODS
A systemic literature search was performed to query published translational and basic science studies on propranolol effects on infantile hemangiomas and cells derived from these lesions.
RESULTS
In experimental studies, propranolol was antiproliferative and cytotoxic against hemangioma endothelial and stem cells and affected infantile hemangioma perivascular cell contractility. Propranolol inhibited migration, network formation, vascular endothelial growth factor A production, and vascular endothelial growth factor receptor 2 activation and down-regulated PI3K/AKT and mitogen-activated protein kinase signaling in hemangioma endothelial cells, but it increased ERK1/2 activity in hemangioma stem cells. At effective clinical doses, measured propranolol plasma concentration is 100 times higher than necessary for complete β-adrenergic receptor blockade, yet was 10 to 100 times less than required to induce hemangioma stem cell death.
CONCLUSIONS
Propranolol targets multiple cell types in infantile hemangiomas by means of β-adrenergic receptor-dependent and -independent mechanisms. Plasma concentration played a significant role. At clinically relevant doses, incomplete infantile hemangioma suppression may explain the rebound phenomenon and worsening ulceration, and propranolol off target effects may lead to commonly reported adverse effects, such as sleep and gastrointestinal disturbances. Propranolol limitations and complications underscore the importance of surgical treatment options in cases of rebound and severe adverse effects. Surgical intervention remains an important treatment choice when parents are hesitant to use propranolol.
Topics: Adrenergic beta-Antagonists; Hemangioma, Capillary; Humans; Infant; Propranolol
PubMed: 33776033
DOI: 10.1097/PRS.0000000000007699 -
The International Journal of... 2022To describe the possible adverse effects of sodium hypochlorite (NaOCl) solutions, high-concentration alcohol solutions, and povidone-iodine products, which are...
PURPOSE
To describe the possible adverse effects of sodium hypochlorite (NaOCl) solutions, high-concentration alcohol solutions, and povidone-iodine products, which are indicated for disinfection of inanimate surfaces against human coronavirus of the severe acute respiratory syndrome (SARS-CoV), on prosthesis materials, including zirconia, lithium disilicate, and acrylic resin.
MATERIALS AND METHODS
A systematic literature research for articles published between January 2010 and February 2020 was conducted in Scopus, PubMed/Medline, Web of Science, Embase, and Science Direct using a combination of the following MeSH/Emtree terms and keywords: sodium hypochlorite, alcohol, ethanol, povidone-iodine, dental ceramic, zirconia, lithium disilicate, and acrylic resin.
RESULTS
A total of 538 studies were identified in the search during initial screening, of which 44 were subject to full-text evaluation, and 24 fulfilled the inclusion criteria. Seven articles on zirconia and lithium disilicate investigated the effect of NaOCl (0.5% and 1%), 96% isopropanol, and 80% ethanol on bond strength after saliva contamination. The remaining articles evaluated color alteration, surface roughness modifications, decrease in flexural strength, and bonding strength of all cleaning agents on acrylic resin.
CONCLUSION
NaOCl (1%) solution for 1 minute is recommended to reduce SARS-CoV infectivity and to minimize the risk of cross-contamination through prosthetic materials. The increase in surface roughness and color alteration were recorded using 1% NaOCl on acrylic resin, but this increase was not clinically significant. A decrease in bonding strength was determined after using 1% NaOCl, 96% isopropanol, and 80% ethanol solutions on lithium disilicate. Silanization before the try-in procedure and the application of the second layer of silane after cleaning methods are recommended to improve the bonding strength.
Topics: 2-Propanol; Acrylic Resins; COVID-19; Ceramics; Dental Bonding; Dental Porcelain; Dental Stress Analysis; Disinfection; Ethanol; Humans; Materials Testing; Pandemics; Povidone-Iodine; Resin Cements; Sodium Hypochlorite; Surface Properties; Zirconium
PubMed: 33662052
DOI: 10.11607/ijp.7151 -
Journal of Perioperative Practice Mar 2022The incidence rates of spinal anaesthesia-induced hypotension vary depending on the surgical procedures. This systematic review and meta-analysis evaluates the efficacy... (Meta-Analysis)
Meta-Analysis
The incidence rates of spinal anaesthesia-induced hypotension vary depending on the surgical procedures. This systematic review and meta-analysis evaluates the efficacy of prophylactic ondansetron in reducing the incidence of spinal anaesthesia-induced hypotension in non-caesarean delivery. Thirteen trials consisting of 1166 patients were included for analysis. Compared to placebo, there is a low quality of evidence that ondansetron was effective in reducing the incidence of spinal anaesthesia-induced hypotension (RR 0.62, 95% CI 0.44 to 0.87; = 0.005) and bradycardia (RR 0.54, 95% CI 0.32 to 0.90; = 0.02). We also found a moderate quality of evidence that ondansetron lowered the number of rescue ephedrine (RR 0.61, 95% CI 0.43 to 0.87; = 0.007). Patients treated with ondansetron have higher mean arterial pressure 15 to 20 minutes after spinal anaesthesia induction and higher systolic arterial pressure 5, 10, 15 and 20 minutes after spinal anaesthesia. The evidence suggests that prophylactic administration of ondansetron results in the reduction of the incidence of spinal anaesthesia-induced hypotension, bradycardia and rescue ephedrine in patients undergoing non-caesarean delivery under spinal anaesthesia.
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Bradycardia; Ephedrine; Humans; Hypotension; Incidence; Ondansetron
PubMed: 33599544
DOI: 10.1177/1750458920964157 -
Cephalalgia : An International Journal... Jun 2021Monoclonal antibodies targeting the calcitonin gene-related peptide pathway (anti-CGRP mAbs) have shown promising efficacy in randomised clinical trials for the...
INTRODUCTION AND OBJECTIVE
Monoclonal antibodies targeting the calcitonin gene-related peptide pathway (anti-CGRP mAbs) have shown promising efficacy in randomised clinical trials for the prevention of episodic and chronic migraine, but no head-to-head comparisons with established treatments are available. We aimed to examine absolute differences in benefit-risk ratios between anti-CGRP mAbs, topiramate and propranolol for the prevention of episodic migraine and between anti-CGRP mAbs, topiramate and onabotulinumtoxinA for the prevention of chronic migraine using a likelihood to help versus harm analysis.
METHODS
The number of patients needed to be treated for a patient to achieve ≥ 50% reduction in migraine days (NNTB) was used as an effect size metric of efficacy. The number of patients needed to be treated for a patient to experience an adverse event that led to treatment discontinuation (NNTH) was used as a measure of risk. Likelihood to help versus harm values - which are the ratios of NNTH:NNTB - were calculated using data from phase 3 randomised clinical trials.
RESULTS
All agents tested were more likely to be beneficial than harmful (likelihood to help versus harm > 1) with the exception of topiramate at 200 mg per day for the prevention of episodic migraine. Anti-CGRP mAbs in all tested doses had higher LHH values than propranolol or topiramate for episodic migraine and onabotulinumtoxinA or topiramate for chronic migraine prevention. Fremanezumab had the highest LHH ratio in episodic migraine and galcanezumab in chronic migraine.
CONCLUSION
This analysis showed that anti-CGRP mAbs exhibit a more favourable benefit-risk ratio than established treatments for episodic and chronic migraine. Head-to-head studies are needed to confirm these results.
Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Propranolol; Protein Precursors; Topiramate; Treatment Outcome
PubMed: 33567891
DOI: 10.1177/0333102421989601 -
British Journal of Clinical Pharmacology Aug 2021To investigate the statistical association between hypoglycaemia and β-blocker use and to define what patient and drug characteristics could potentially increase the...
AIMS
To investigate the statistical association between hypoglycaemia and β-blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence.
METHODS
We investigated the relationship between pharmacological parameters of β-blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values of P < .05). We also performed a systematic review of clinical studies on this association.
RESULTS
Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40-9.03]), celiprolol (2.35 [1.35-4.10]), propranolol (2.14 [1.87-2.46]) and bisoprolol (1.42 [1.25-1.61]). Paediatric cases (n = 310) showed a positive association with hypoglycaemia for long half-life drugs (odds ratio [95% confidence interval]: 2.232 [1.398-3.563]) and a negative association for β1-selectivity (0.644 [0.414-0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (n total participants = 575), 6.6% for atenolol (n = 30) and 10% for carvedilol (n = 20).
CONCLUSION
Nadolol appears to be the β-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective β-blockers seem to increase the risk for its occurrence.
Topics: Adrenergic beta-Antagonists; Carvedilol; Child; Humans; Hypoglycemia; Odds Ratio; Pharmacovigilance
PubMed: 33506522
DOI: 10.1111/bcp.14754 -
Kardiologiia Dec 2020This article presents results of a systematic review, which was designed for evaluating the effect of combination treatment with ivabradine and metoprolol on heart rate,...
This article presents results of a systematic review, which was designed for evaluating the effect of combination treatment with ivabradine and metoprolol on heart rate, frequency of angina attacks, frequency of using short-acting nitrates, and angina severity. The analysis included data from three large observational studies on efficacy of the ivabradine and metoprolol tartrate combination in patients with chronic angina. Results of the analysis supported the efficacy of the metoprolol and ivabradine combination in clinical practice, which provided effective decreases in the heart rate, frequency of angina attacks, requirement for short-acting nitrates, and alleviation of angina severity. The studies demonstrated good tolerability of this treatment.
Topics: Adrenergic beta-Antagonists; Angina, Stable; Benzazepines; Drug Therapy, Combination; Heart Rate; Humans; Ivabradine; Metoprolol; Treatment Outcome
PubMed: 33487156
DOI: 10.18087/cardio.2020.11.n1357 -
The British Journal of Ophthalmology May 2022To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP).
METHODS
A systematic literature review adapted from the Li (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated.
RESULTS
A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%.
CONCLUSION
LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.
Topics: Amides; Antihypertensive Agents; Bayes Theorem; Betaxolol; Bimatoprost; Brimonidine Tartrate; Carteolol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Network Meta-Analysis; Ocular Hypertension; Prostaglandins A; Prostaglandins F, Synthetic; Timolol; Travoprost
PubMed: 33397657
DOI: 10.1136/bjophthalmol-2020-317262 -
The Cochrane Database of Systematic... Dec 2020Age-related macular degeneration (AMD) is a highly prevalent condition in an ever-increasing elderly population. Although insidious in the early stages, advanced AMD... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related macular degeneration (AMD) is a highly prevalent condition in an ever-increasing elderly population. Although insidious in the early stages, advanced AMD (neovascular and atrophic forms) can cause significant visual disability and economic burden on health systems worldwide. The most common form, geographic atrophy, has no effective treatment to date, whereas neovascular AMD can be treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Geographic atrophy has a slow disease progression and patients tend to have preserved central vision until the final stages. This tendency, coupled with the use of modern imaging modalities, provides a large window of opportunity to intervene with validated methods to assess treatment efficacy. As geographic atrophy is an increasingly common condition with no effective intervention, many treatments are under investigation, one of which is visual cycle modulators. These medications have been shown to reduce lipofuscin accumulation in pre-clinical studies that have led to several clinical trials, reviewed herein.
OBJECTIVES
To assess the efficacy and safety of visual cycle modulators for the prevention and treatment of geographic atrophy secondary to AMD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); MEDLINE Ovid; Embase Ovid; Web of Science Core Collection; Scopus; Association for Research in Vision and Ophthalmology (ARVO) website; ClinicalTrials.gov and the WHO ICTRP to 11 January 2020 with no language restrictions. We also searched using the reference lists of reviews and existing studies and the Cited Reference Search function in Web of Science to identify further relevant studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-randomised clinical studies (if available) that compared visual cycle modulators to placebo or no treatment (observation) in people diagnosed with AMD (early, intermediate or geographic atrophy).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed risk of bias in the included studies and extracted data. Both authors entered data into RevMan 5. We resolved discrepancies through discussion. We graded the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included three RCTs from the USA; one of these had clinical sites in Germany. Two studies compared emixustat to placebo while the other compared fenretinide to placebo. All assigned one study eye per participant and, combined, have a total of 821 participants with a majority white ethnicity (97.6%). All participants were diagnosed with geographic atrophy due to AMD based on validated imaging modalities. All three studies have high risk of attrition bias mainly due to ocular adverse effects of emixustat and fenretinide. We considered only one study to be adequately conducted and reported with high risk of bias in only one domain (attrition bias). We considered the other two studies to be poorly reported and to have high risk of attrition bias and reporting bias. People with geographic atrophy treated with emixustat may not experience a clinically important change in best-corrected visual acuity (BCVA) between baseline and 24 months compared to people treated with placebo (mean difference (MD) 1.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (CI) -2.34 to 6.14, low-certainty evidence). Emixustat may also result in little or no difference in loss of 15 ETDRS letters or more of BCVA compared with placebo at 24 months (16.4% versus 18%) (risk ratio (RR) 0.91, 95% CI 0.59 to 1.4, low-certainty evidence). In terms of disease progression, emixustat may result in little or no difference in the annual growth rate of geographic atrophy compared with placebo (mean difference MD 0.09 mm/year (95% CI -0.26 to 0.44, low-certainty evidence). All three studies reported adverse events of both drugs (emixustat: moderate-certainty evidence; fenretinide: low-certainty evidence). The main adverse events were ocular in nature and associated with the mechanism of action of the drugs. Delayed dark adaptation (emixustat: 54.5%; fenretinide: 39.3%) and chromatopsia (emixustat: 22.6%; fenretinide: 25.2%) were the most common adverse events reported, and were the most prevalent reasons for study dropout in emixustat trials. These effects were dose-dependent and resolved after drug cessation. No specific systemic adverse events were considered related to emixustat; only pruritus and rash were considered to be due to fenretinide. One emixustat study reported six deaths, none deemed related to the drug. None of the included RCTs reported the other pre-specified outcomes, including proportion of participants losing 10 letters or more, and mean change in macular sensitivity. We planned to investigate progression to advanced AMD (geographic atrophy or neovascular AMD) in prevention studies, including participants with early or intermediate AMD, but we identified no such studies. Two of the included studies reported an additional outcome - incidence of choroidal neovascularisation (CNV) - that was not in our published protocol. CNV onset may be reduced in those treated with emixustat but the evidence was uncertain (risk ratio (RR) 0.67, 95% CI 0.27 to 1.65, low-certainty evidence), or fenretinide (RR 0.5, 95% CI 0.26 to 0.98, low-certainty evidence) compared to placebo. A dose-dependent relationship was observed with emixustat.
AUTHORS' CONCLUSIONS
There is limited evidence to support the use of visual cycle modulators (emixustat and fenretinide) for the treatment of established geographic atrophy due to AMD. The possible reduction in the incidence of CNV observed with fenretinide, and to a lesser extent, emixustat, requires formal assessment in focused studies.
Topics: Aged; Aged, 80 and over; Choroidal Neovascularization; Clinical Trials, Phase II as Topic; Disease Progression; Fenretinide; Geographic Atrophy; Humans; Incidence; Macular Degeneration; Phenyl Ethers; Placebos; Propanolamines; Randomized Controlled Trials as Topic; Visual Acuity; Watchful Waiting
PubMed: 33331670
DOI: 10.1002/14651858.CD013154.pub2 -
BMJ Open Oct 2020Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after open heart surgery. This systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after open heart surgery. This systematic review and meta-analysis aimed to investigate metoprolol compared with other treatments for prophylaxis against POAF.
METHODS
We searched CENTRAL, MEDLINE, EMBASE and trial registries for randomised controlled trials that evaluated metoprolol for preventing the occurrence of POAF after surgery against other treatments or placebo. Random-effects model was used for estimating the risk ratios (RRs) and mean differences with 95% CIs.
RESULTS
Nine trials involving 1570 patients showed metoprolol reduced POAF compared with placebo (416 patients; RR 0.46, 95% CI 0.33 to 0.66; I²=21%; risk difference (RD) -0.19, 95% CI -0.28 to -0.10). However, metoprolol increased the risk of POAF compared with carvedilol (159 patients; RR 1.59, 95% CI 1.20 to 2.12; I²=4%; RD 0.13, 95% CI 0.06 to 0.20). There was no difference when compared with sotalol or amiodarone. The occurrence of cardiovascular conditions after drugs administration or death between the groups was not different. The overall quality of evidence was moderate to high. Subgroup analysis and funnel plot were not performed.
CONCLUSIONS
Metoprolol is effective in preventing POAF compared with placebo and showed no difference with class III antiarrhythmic drugs. Death and thromboembolism are associated with open heart surgery, but not significant in relation to the use of metoprolol.
PROSPERO REGISTRATION NUMBER
CRD42019131585.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Metoprolol; Postoperative Complications
PubMed: 33130564
DOI: 10.1136/bmjopen-2020-038364 -
Contact Dermatitis Jan 2021The use of alcoholic-based hand rubs (ABHRs) is an important tool for hand hygiene, especially in times of the COVID-19 pandemic. Possible irritant effects of ABHR may...
BACKGROUND
The use of alcoholic-based hand rubs (ABHRs) is an important tool for hand hygiene, especially in times of the COVID-19 pandemic. Possible irritant effects of ABHR may prevent their use by persons at risk of infection.
METHODS
This systematic review is based on a PubMed search of articles published between January 2000 and September 2019 in English and German, and a manual search, related to the irritation potential of alcohol-based disinfectants restricted to n-propanol (1-propanol) and its structural isomer isopropanol (isopropyl alcohol, 2-propanol).
RESULTS
The majority of the included studies show a low irritation potential of n-propanol alone. However, recent studies provide evidence for significant barrier damage effects of repeated exposure to 60% n-propanol in healthy, as well as atopic skin in vivo. The synergistic response of combined irritants, (ie, a combination of n-propanol or isopropanol with detergents such as sodium lauryl sulfate) is greater, compared with a quantitatively identical application of the same irritant alone.
CONCLUSION
While recent studies indicate a higher risk of skin irritation for n-propanol and isopropanol than reported in the past, this risk still seems to be lower than that for frequent handwashing with detergents, as recommended by some to prevent COVID-19 infections.
Topics: 1-Propanol; 2-Propanol; Anti-Infective Agents, Local; COVID-19; Dermatitis, Irritant; Hand Disinfection; Humans
PubMed: 33063847
DOI: 10.1111/cod.13722