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Journal of Clinical Pharmacology Feb 2024The optimal therapeutic management of cyclic vomiting syndrome (CVS) remains elusive. The objective of this study was to document our clinical experience in the... (Meta-Analysis)
Meta-Analysis
The optimal therapeutic management of cyclic vomiting syndrome (CVS) remains elusive. The objective of this study was to document our clinical experience in the Pediatric Department of San Marco Hospital and to survey the literature on pediatric CVS treatment, aiming to update the guidance on the most effective treatment strategies for this not-so-uncommon condition. Data from 70 patients with CVS, admitted to our Pediatric Department between September 2011 and December 2021, were aggregated and included in the study. A systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) method. Treatment responses, as observed both in the literature and in our own experience, are variable. In our cohort, topiramate demonstrated superiority over other pharmacological treatments, exhibiting an efficacy of 85% in the patients treated. A universally accepted treatment protocol for pediatric CVS has yet to be established. The efficacy of first-line treatments is generally suboptimal, suggesting that topiramate might serve as a safe and effective primary therapeutic option for pediatric CVS.
Topics: Humans; Child; Topiramate; Vomiting; Treatment Outcome
PubMed: 37867371
DOI: 10.1002/jcph.2374 -
Translational Stroke Research Oct 2023Cerebral cavernous malformation (CCM), either sporadic or familial, is a devastating vascular malformation affecting the central nervous system that can present with... (Review)
Review
Cerebral cavernous malformation (CCM), either sporadic or familial, is a devastating vascular malformation affecting the central nervous system that can present with intracerebral hemorrhage, seizure, and new focal neurologic deficits resulting in substantial morbidity and mortality. To date, there is no effective evidence-based preventive regimen. There have been several preclinical and clinical studies investigating the potential mechanisms and benefits of beta-blockers, especially on propranolol. We aimed to conduct a systematic review on the published literature investigating the use of beta-blockers in the treatment of CCM, including both preclinical and clinical studies between 2008 and 2023 using public databases. A total of 2 preclinical studies and 6 clinical studies met the inclusion/exclusion criteria and were included. Data was extracted and synthesized from 5 clinical studies for meta-analysis. The meta-analysis failed to demonstrate a statistically significant protective effect of beta-blockers in preventing intracerebral hemorrhage or developing focal neurologic deficits in subjects with CCM (overall effect = 0.78 (0.20, 3.11), p = 0.73). Overall, there was a paucity of high quality clinical trials, partially due to limited cases of CCM. Addressing this gap may require collaborative efforts at a national or international level. In this review, we summarized all barriers and opportunities on this topic. Additionally, we proposed establishing an evidence-based approach on the use of beta-blockers in preventing recurrent hemorrhage and focal neurological deficits in patients with CCM.
PubMed: 37857790
DOI: 10.1007/s12975-023-01199-5 -
Cureus Sep 2023A precarious complication of thyrotoxicosis, or thyroid storm, is the increased risk of cardiomyopathy, which leads to circulatory collapse and cardiopulmonary arrest.... (Review)
Review
A precarious complication of thyrotoxicosis, or thyroid storm, is the increased risk of cardiomyopathy, which leads to circulatory collapse and cardiopulmonary arrest. It is crucial to promptly identify this condition to prevent significant deterioration of the left ventricular function and cardiogenic shock. This article seeks to examine published research that emphasizes the connection between thyroid storm and beta-blocker usage in relation to cardiogenic collapse and provides management recommendations. The search was performed on September 9, 2022, using PubMed, Science Direct, and Google Scholar libraries. A systematic exploration was carried out using the keywords AND AND cardiac arrest AND beta blocker. The use of beta blockers as part of thyroid storm management was linked to the development of cardiogenic collapse and cardiac arrest. Ultra-short-acting beta-blockers like esmolol were a safer option than propranolol in treating patients with a thyrotoxic storm.
PubMed: 37799246
DOI: 10.7759/cureus.44655 -
European Journal of Neurology Dec 2023The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European... (Review)
Review
BACKGROUND
The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management.
METHODS
A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.
RESULTS
Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.
CONCLUSIONS
The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Topics: Humans; Chorea; Tetrabenazine; Levodopa; Carbidopa; Clonazepam; Methylphenidate
PubMed: 37694681
DOI: 10.1111/ene.16038 -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
Cureus Aug 2023The most common cause of portal hypertension is liver cirrhosis. Portal hypertension causes many complications in cirrhotic patients; a significant complication is the... (Review)
Review
The Efficacy of Carvedilol in Comparison to Propranolol in Reducing the Hepatic Venous Pressure Gradient and Decreasing the Risk of Variceal Bleeding in Adult Cirrhotic Patients: A Systematic Review.
The most common cause of portal hypertension is liver cirrhosis. Portal hypertension causes many complications in cirrhotic patients; a significant complication is the formation of varices and the subsequent life-threatening variceal bleeding due to elevated portal venous pressures. Hepatic venous pressure gradient (HVPG) is the gold standard for measuring portal hypertension and guides management. Pharmacological treatments lower the HVPG, preventing the progression of varices and subsequent variceal bleeding. The pharmacological treatments frequently used in primary and secondary prophylaxis of a variceal bleed are nonselective beta (β)-adrenergic blockers. Propranolol was the first nonselective β-adrenergic blocker used for lowering HVPG and has been well studied. However, in the past decade, clinical trials have shown that carvedilol has been more effective. This study aims to establish whether carvedilol is more effective than propranolol in reducing the hepatic venous pressure gradient and decreasing the risk of variceal bleeding in adult cirrhotic patients. A systematic review has been conducted to gather relevant clinical trials comparing drugs and their effects on HVPG. Four databases: PubMed (Medical Literature Analysis and Retrieval System Online (MEDLINE)), Google Scholar, the Cochrane Library, and ScienceDirect, were analyzed, and records from January 1, 1999, to January 1, 2023, were chosen. There were a total of 1,235 potentially eligible records across the four databases. Using the eligibility criteria for this systematic review, seven studies of 533 patients were included. Across all seven clinical trials, it was found that carvedilol reduced HVPG more than propranolol and decreased the risk of variceal bleeding in adult cirrhotic patients.
PubMed: 37577269
DOI: 10.7759/cureus.43253 -
Frontiers in Pharmacology 2023Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in...
Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients. To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis. We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case‒control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed. A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10), = 0.000, and I = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62-1.44) or timolol (OR = 1.32 and 95%CI 0.44-3.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64-0.86) and carvedilol (OR = 0.62 and 95%CI 0.52-0.74), respectively. Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America. identifier https://CRD42023434175, https://www.crd.york.ac.uk/PROSPERO/.
PubMed: 37538177
DOI: 10.3389/fphar.2023.1216059 -
Cephalalgia : An International Journal... Jun 2023Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain.
METHODS
Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed.
RESULTS
In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil.
CONCLUSION
Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines. The study was registered at PROSPERO (CRD42017079176).
Topics: Humans; Female; Adult; Male; Blood Pressure; Migraine Disorders; Calcium Channel Blockers; Propranolol; Headache
PubMed: 37350141
DOI: 10.1177/03331024231183166 -
Translational Psychiatry Jun 2023Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories....
Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories. Not all patients benefit, however, and there is room for improvement of efficacy. Pharmacologically augmenting trauma memory modulation in the context of tf-PT may help optimise treatment outcome. To systematically review effects of pharmacologically augmented memory modulation in the context of tf-PT for PTSD (PROSPERO preregistration ID: CRD42021230623). We conducted a systematic review of randomised controlled trials of psychotherapy treatment for PTSD. We included placebo-controlled studies that augmented at least one treatment session pharmacologically targeting memory extinction or reconsolidation. We calculated post-treatment between group (pharmacological augmentation vs placebo control) effect sizes of PTSD symptom severity. We included 13 RCTs. There was large heterogeneity in augmentation procedure and methodological quality. Four studies showed significantly greater PTSD symptom reduction in the pharmacological augmentation group (propranolol, hydrocortisone, dexamethasone, D-cycloserine) compared to placebo. Seven studies showed no significant effect of pharmacological augmentation compared to placebo (D-cycloserine, rapamycin, mifepristone, propranolol, mifepristone combined with D-cycloserine, methylene blue). Two studies showed significantly smaller PTSD symptom reduction in the pharmacological augmentation group (D-cycloserine, dexamethasone) compared to placebo. Results of pharmacological augmentation were mixed overall and heterogenous for the pharmacological agents tested in more than one study. Additional studies and replications are needed to identify which pharmacological agents work, in which combination and to identify patient groups that benefit most to tailor PTSD treatment.
Topics: Humans; Cycloserine; Dexamethasone; Mifepristone; Propranolol; Psychotherapy; Stress Disorders, Post-Traumatic; Randomized Controlled Trials as Topic
PubMed: 37321998
DOI: 10.1038/s41398-023-02495-2 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887