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Journal of Neuroimmune Pharmacology :... Jun 2024Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary... (Review)
Review
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary injury. Administration of propranolol for TBI maydecrease mortality and improve functional outcomes. However, it is our sense that its use has not been universally adopted due to low certainty evidence. The literature was reviewed to explore the mechanism of propranolol as a therapeutic intervention in TBI to guide future clinical investigations. Medline, Embase, and Scopus were searched for studies that investigated the effect of propranolol on TBI in animal models from inception until June 6, 2023. All routes of administration for propranolol were included and the following outcomes were evaluated: cognitive functions, physiological and immunological responses. Screening and data extraction were done independently and in duplicate. The risk of bias for each individual study was assessed using the SYCLE's risk of bias tool for animal studies. Three hundred twenty-three citations were identified and 14 studies met our eligibility criteria. The data suggests that propranolol may improve post-TBI cognitive and motor function by increasing cerebral perfusion, reducing neural injury, cell death, leukocyte mobilization and p-tau accumulation in animal models. Propranolol may also attenuate TBI-induced immunodeficiency and provide cardioprotective effects by mitigating damage to the myocardium caused by oxidative stress. This systematic review demonstrates that propranolol may be therapeutic in TBI by improving cognitive and motor function while regulating T lymphocyte response and levels of myocardial reactive oxygen species. Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.
Topics: Propranolol; Animals; Brain Injuries, Traumatic; Neuroprotective Agents; Humans; Disease Models, Animal; Drug Evaluation, Preclinical; Adrenergic beta-Antagonists
PubMed: 38900343
DOI: 10.1007/s11481-024-10121-1 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Journal of Gastrointestinal Surgery :... Mar 2024This systematic review and meta-analysis aimed to assess the efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) against the combined treatment... (Meta-Analysis)
Meta-Analysis Review
Safety and efficacy of transjugular intrahepatic portosystemic shunts vs endoscopic band ligation plus propranolol in patients with cirrhosis with portal vein thrombosis: a systematic review and meta-analysis.
BACKGROUND
This systematic review and meta-analysis aimed to assess the efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) against the combined treatment of endoscopic band ligation (EBL) and propranolol in managing patients with cirrhosis diagnosed with portal vein thrombosis (PVT).
METHODS
A literature search from inception to September 2023 was performed using MEDLINE, the Cochrane Library, Web of Science, and Scopus. Independent screening, data extraction, and quality assessment were performed. The main measured outcomes were the incidence and recurrence of variceal bleeding (VB), hepatic encephalopathy, and overall survival.
RESULTS
A total of 5 studies were included. For variceal eradication, there was initially no significant difference between the groups; however, after sensitivity analysis, a significant effect emerged (risk ratio [RR], 1.55; P < .0001). TIPS was associated with a significant decrease in the incidence of VB (RR, 0.34; P < .0001) and a higher probability of remaining free of VB in the first 2 years after the procedure (first year: RR, 1.41; P < .0001; second year: RR, 1.58; P < .0001). TIPS significantly reduced the incidence of death due to acute GI bleeding compared with EBL + propranolol (RR, 0.37; P = .05).
CONCLUSION
TIPS offers a comprehensive therapeutic advantage over the combined EBL and propranolol regimen, especially for patients with cirrhosis with PVT. Its efficacy in variceal eradication, reducing rebleeding, and mitigating death risks due to acute GI bleeding is evident.
Topics: Humans; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Liver Cirrhosis; Liver Diseases; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Propranolol; Thrombosis
PubMed: 38445926
DOI: 10.1016/j.gassur.2023.12.031 -
European Journal of Clinical... Jun 2024To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor. (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor.
METHODS
A comprehensive literature search was performed across multiple databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database, PubMed, Embase, and the Cochrane Library. All publicly published randomized controlled trials (RCTs) of propranolol combined with oxytocin compared to the use of oxytocin alone in labor were collected. After screening the literature and extracting data, the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 recommended bias risk assessment tool was used to assess the quality of the included studies. A meta-analysis was conducted using RevMan 5.3 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence for outcome measures.
RESULTS
Meta-analysis results showed that the group receiving propranolol combined with oxytocin was more capable of reducing the cesarean section rate (eight studies, 815 women, RR = 0.67, 95% CI (0.53, 0.86), P = 0.001) and shortening the duration of the latent phase (two studies, 206 women, MD = - 1.20, 95% CI (- 1.97, - 0.43), P = 0.002) and the duration of the active phase on day 1 (two studies, 296 women, MD = - 0.69, 95% CI (- 0.83, - 0.54), P < 0.00001), compared to the oxytocin monotherapy group. No significant difference was found between the two groups in terms of the 5-min Apgar score (five studies, 609 women, MD = - 0.05, 95% CI (- 0.14, 0.04), P = 0.32) and the rate of admissions to the Neonatal Intensive Care Unit (NICU) (three studies, 359 women, RR = 0.82, 95% CI (0.38, 1.79), P = 0.62).
CONCLUSION
The combined use of propranolol and oxytocin can significantly reduce the cesarean section rate, shorten the duration of the latent phase and the duration of the active phase on day 1, and is safe. However, due to the limitations, the conclusions of this article still need to be verified by large-sample, multicenter, rigorously designed high-quality clinical RCTs.
TRIAL REGISTRATION
Registration number is INPLASY202390107.
Topics: Humans; Propranolol; Oxytocin; Pregnancy; Female; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Cesarean Section; Labor, Obstetric; Oxytocics
PubMed: 38436704
DOI: 10.1007/s00228-024-03659-9 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Hepatology Communications Feb 2024It has been suggested that a relevant proportion of patients do not respond to nonselective beta-blockers (NSBB)s, which raises questions regarding the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It has been suggested that a relevant proportion of patients do not respond to nonselective beta-blockers (NSBB)s, which raises questions regarding the need for individualized therapy. The existence of potential heterogeneity in the treatment response can be assessed using the variability ratio (VR) of the outcome measurement (in this case, HVPG) between the treated and placebo groups. We conducted a systematic review and meta-analysis of randomized controlled trials to assess the potential heterogeneity in the portal pressure response to NSBBs.
METHODS
After a systematic search, we quantified the heterogeneity of treatment response with the VR between the treatment and control groups, with VR > 1 indicating potential heterogeneity. We used a similar approach to compare carvedilol with propranolol and statins with placebo.
RESULTS
We identified 18 studies that included 965 patients. A comparison between beta-blockers and placebo showed a pooled VR of 0.99 (95% CI:0.87-1.14), which suggests a homogeneous HVPG response to NSBB at the individual patient level (ie, no evidence to support that some patients responded to beta-blockers and others did not). For the comparison between carvedilol and propranolol, pooled VR was 0.97 (95% CI 0.82-1.14), suggesting that carvedilol achieves a greater average response (rather than an increase in the proportion of responders). There was no evidence of a heterogeneous response to statins.
CONCLUSION
Our analysis did not support the existence of a heterogeneous patient-by-patient response to NSBBs in cirrhosis. These findings challenge the concept of personalized therapy based on portal pressure response and indicate that routine portal pressure measurement may not be necessary to guide NSBB therapy.
Topics: Humans; Propranolol; Carvedilol; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Adrenergic beta-Antagonists; Hypertension, Portal
PubMed: 38285880
DOI: 10.1097/HC9.0000000000000321 -
Annals of Medicine Dec 2024Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association.
METHODS
PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.
RESULTS
Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; = 0.08) and multivariable regression modelling (adjusted HR = 0.86; = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses.
CONCLUSIONS
NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.
Topics: Humans; Ascites; End Stage Liver Disease; Severity of Illness Index; Liver Cirrhosis; Adrenergic beta-Antagonists; Kidney Diseases
PubMed: 38271554
DOI: 10.1080/07853890.2024.2305935 -
The Journal of Headache and Pain Dec 2023Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults.
METHODS
We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis.
FINDINGS
We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small.
INTERPRETATION
All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications.
REGISTRATION
PROSPERO (number CRD42021265990).
Topics: Adult; Humans; Topiramate; Network Meta-Analysis; Migraine Disorders; Treatment Outcome; Headache; Double-Blind Method
PubMed: 38057728
DOI: 10.1186/s10194-023-01696-w -
Current Allergy and Asthma Reports Dec 2023To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients.
RECENT FINDINGS
Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.
Topics: Humans; Epistaxis; Tranexamic Acid; Timolol; Telangiectasia, Hereditary Hemorrhagic; Propranolol; Network Meta-Analysis; Tacrolimus; Estriol; Estradiol; Tamoxifen
PubMed: 37995018
DOI: 10.1007/s11882-023-01116-8 -
American Journal of Ophthalmology Mar 2024To learn more about the effectiveness of oral propranolol as a therapeutic alternative for preterm newborns with pre-existing retinopathy of prematurity (ROP) as well as... (Meta-Analysis)
Meta-Analysis
PURPOSE
To learn more about the effectiveness of oral propranolol as a therapeutic alternative for preterm newborns with pre-existing retinopathy of prematurity (ROP) as well as an early prevention method for ROP, one of the most common but avoidable causes of juvenile blindness.
STUDY DESIGN
Meta-analysis of relevant literature.
METHODS
A total of 3464 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, finally, a total of 8 studies were deemed suitable for review. Following the PRISMA guidelines, published literature was systematically assessed up to May 10, 2023. Trials and observational studies were included in which beta blockage was used to prevent severe ROP (defined as stage ≥3 or requiring treatment). A total of 3646 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, a total of 8 studies were deemed suitable for review.
RESULTS
The use of propranolol is linked to a lower risk of disease development in ROP compared to other therapies or control groups, according to the overall risk ratio of 0.59 (95% CI = 0.42, 0.82; P = .002, I = 41%). Additionally, the overall risk ratio for plus disease is 0.42 (95% CI = 0.23, 0.78; P = .006, I = 0%), for laser photocoagulation is 0.48 (95% CI = 0.31, 0.74; P = .001; I = 2%), and for intravitreal injection of VEGF is 0.43 (95% CI = 0.24, 0.74; P = 0.003, I = 0%), suggesting that use of propranolol may reduce the likelihood of developing a disease such as plus disease, requiring laser photocoagulation or necessitating intravitreal injection of vascular endothelial growth factor for ROP, respectively. No statistically significant heterogeneity was found in this study (P > .10, I = 50%). It can be concluded from this that the results of the chosen studies were sufficiently comparable and consistent.
CONCLUSION
This study showed that oral propranolol given as a preventive treatment in premature newborns successfully prevented severe ROP. Propranolol dosage and timing must now be carefully considered in the context of the study population, as these factors may have a major impact on the observed outcomes and treatment success.
Topics: Humans; Infant, Newborn; Adrenergic beta-Antagonists; Angiogenesis Inhibitors; Infant, Premature; Propranolol; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A
PubMed: 37979602
DOI: 10.1016/j.ajo.2023.11.012