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Respiratory Investigation Mar 2024The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma.
METHODS
We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model.
SYSTEMATIC REVIEW REGISTRATION
University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824).
RESULTS
No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups.
CONCLUSIONS
Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.
Topics: Adult; Humans; Macrolides; Quality of Life; Disease Progression; Asthma; Anti-Bacterial Agents; Adrenal Cortex Hormones
PubMed: 38211545
DOI: 10.1016/j.resinv.2023.12.015 -
The Journal of Headache and Pain Sep 2023Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis.
METHODS
A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo-controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation.
RESULTS
Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06).
CONCLUSIONS
Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large-scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.
Topics: Humans; Flunarizine; Headache; Migraine Disorders; Migraine with Aura; Research Design; Transcription Factors
PubMed: 37723437
DOI: 10.1186/s10194-023-01657-3 -
Frontiers in Pharmacology 2023A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial...
A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial fibrillation (AF) undergoing dialysis, primarily due to limited retrospective studies. Therefore, the objective of this study was to evaluate the existing data and propose a practical protocol for the clinical utilization of DOACs in ESRD patients with AF undergoing dialysis. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for clinical studies evaluating DOACs in ESRD patients with AF on dialysis published up to 2 February 2023. DOACs included warfarin, dabigatran, apixaban, edoxaban, and rivaroxaban. The outcomes were mortality, ischemic stroke, hemorrhagic stroke, any stroke, gastrointestinal bleeding, major bleeding, intracranial bleeding, and minor bleeding. Compared with placebo, apixaban (HR = 0.97, 95% CI: 0.88-1.07), rivaroxaban (HR = 0.91, 95% CI: 0.76-1.10), and warfarin (HR = 0.96, 95% CI: 0.90-1.01) did not reduce mortality. Regarding direct comparisons of mortality, the comparisons of warfarin vs. apixaban (HR = 0.99, 95% CI: 0.92-1.06), placebo vs. warfarin (HR = 1.04, 95% CI: 0.99-1.11), and rivaroxaban vs. warfarin (HR = 0.96, 95% CI: 0.80-1.14) did not significantly reduce mortality. Based on the surface under the cumulative ranking curve, rivaroxaban (75.53%), warfarin (62.14%), and apixaban (45.6%) were the most effective interventions for managing mortality, and placebo (16.74%) was the worst. In conclusion, rivaroxaban demonstrated efficacy in reducing mortality and the incidence of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage. Dabigatran is recommended for the prevention of hemorrhagic stroke. However, caution should be exercised due to the risk of major bleeding. Warfarin can effectively reduce minor bleeding but does not offer significant protection against gastrointestinal or intracranial bleeding. Apixaban was not recommended for mortality reduction or for preventing ischemic or hemorrhagic strokes. Further research will be necessary to establish specific clinical protocols.
PubMed: 38161701
DOI: 10.3389/fphar.2023.1320939 -
Cureus Oct 2023Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved to treat dyslipidaemia. However, there is a lack of knowledge on the most efficient... (Review)
Review
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved to treat dyslipidaemia. However, there is a lack of knowledge on the most efficient PCSK9 therapies that target PCSK9 for secondary prevention in subjects at high risk for cardiovascular (CV) events. Thus, this study aimed to assess the efficacy and safety of anti-PCSK9 antibodies in randomized controlled trials (RCTs). A comprehensive review of the available literature was done to identify RCTs that compared the use of PCSK9 inhibitors coupled with placebo or ezetimibe for the secondary prevention of CV events in patients on statin-background therapy. All-cause mortality was the major efficacy endpoint, while severe adverse events were the key safety outcome. A random effects model was used, and data were presented as risk ratio (RR) or risk difference with their corresponding 95% confidence intervals (CI). The heterogeneity of the publications was determined using Cochran's Q test, and publication bias was visually examined using funnel plots. All the chosen studies' quality was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI). Forty-one studies (76,304 patients: 49,086 on evolocumab, and 27,218 on alirocumab) were included, and their years of publication spanned from 2010 to 2023. Overall, no significant differences were observed in CV and all-cause mortality between PCSK9 inhibitors and controls. However, alirocumab use was linked to a reduced risk of all-cause death compared to control, but not evolocumab. Each of the drugs, evolocumab and alirocumab, significantly reduced the risk of myocardial infarction (MI), coronary revascularization, and ischemic stroke. In comparison to the control therapy, the risk of major detrimental sequelae was significantly reduced by alirocumab therapy in the subgroup analysis of each PCSK9 inhibitor, whereas evolocumab treatment did not demonstrate significant differences (RR = 0.88; 95% CI = 0.72-1.04; evolocumab: RR = 0.99; 95% CI = 0.87-1.11). Both evolocumab and alirocumab are well-tolerated, safe medications that significantly lower low-density lipoprotein (LDL) levels.
PubMed: 37937036
DOI: 10.7759/cureus.46605 -
Psychiatry Investigation Dec 2023To find the safety of long-acting injectable antipsychotics (LAIs) compared to each other, and/or placebo in the treatment of schizophrenia (SCZ) and/or schizoaffective...
OBJECTIVE
To find the safety of long-acting injectable antipsychotics (LAIs) compared to each other, and/or placebo in the treatment of schizophrenia (SCZ) and/or schizoaffective disorder (SZA).
METHODS
We performed a systematic review and a network meta-analysis of randomized controlled trials (RCTs) comparing the safety of LAIs versus other LAIs or placebo in adults diagnosed with SCZ or SZA. The primary outcomes were treatment emergent adverse events (TEAEs), serious treatment emergent adverse events (STEAEs), and deaths. The secondary outcomes included treatment discontinuations due to adverse events and all-cause discontinuations.
RESULTS
Seventeen RCTs were included (n=7,908). There were no significant differences between LAIs and placebo in the risk of presenting TEAEs. LAIs had a significant lower risk of presenting STEAEs except for aripiprazole. No significant differences in deaths were found. LAIs showed a significant protective effect against all-cause discontinuation, except for haloperidol. Only aripiprazole had a significantly lower risk of treatment discontinuation due to adverse events.
CONCLUSION
We found no significant differences in the risk of presenting TEAEs between LAIs and placebo. The majority of LAIs had a significantly lower risk of presenting STEAEs than placebo. Development of international guidelines for the report of safety outcomes related to antipsychotics especially for LAIs in clinical trials could minimize report and interpretation biases and improve the accuracy of posterior meta-analysis.
PubMed: 38163650
DOI: 10.30773/pi.2022.0216 -
The Journal of Hospital Infection Sep 2023This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Part I), alleviating clinical symptoms or severity of disease (Part II), and decreasing the incidence of SARS-CoV-2 infection (Part III).
METHODS
Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) with restrictions were searched up to 3 March 2023. Twenty-three studies (22 RCTs and one NRCT) met the inclusion criteria for this systematic review.
RESULTS
Five RCTs (454 patients and nine interventions) in Part I were eligible for NMA. The NMA results showed that, in comparison with no rinse, sodium chloride (NaCl) was the most effective mouth rinse for reducing the viral load, followed by povidone-iodine (PVP-I), ß-cyclodextrin + citrox (CDCM), hydrogen peroxide (HP), chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), placebo and hypochlorous acid (HClO). However, these results were not significant. Based on surface under the cumulative ranking curve scores, PVP-I was likely to be the most efficacious mouth rinse for reducing SARS-CoV-2 viral load, followed by CDCM, HP, NaCl, CHX, CPC, placebo, no rinse and HClO.
CONCLUSION
Due to heterogeneity of the primary studies, the effectiveness of different mouth rinses to reduce viral infectivity, improve clinical symptoms or prevent SARS-CoV-2 infection remains inconclusive.
Topics: Humans; COVID-19; Mouthwashes; Povidone-Iodine; SARS-CoV-2; Sodium Chloride; Network Meta-Analysis; Hydrogen Peroxide; Mouth
PubMed: 37419189
DOI: 10.1016/j.jhin.2023.06.022 -
Scientific Reports Sep 2023Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic... (Meta-Analysis)
Meta-Analysis
Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic agent for the treatment of CACS. In this systematic review, we assessed the efficacy of oral anamorelin treatment for patients with CACS. On July 6, 2022, we systematically searched the following databases for randomized controlled trials (RCTs) of adults with CACS comparing oral anamorelin versus placebo: CENTRAL, PubMed, EMBASE, and ICHUSHI. The primary outcomes were total body weight (TBW), patient-reported quality of life (QOL), and adverse events (AEs). Secondary outcomes included lean body mass (LBM), overall survival (OS), non-dominant hand grip strength (HGS), and appetite. We included seven RCTs with a total of 1944 CACS patients. Anamorelin significantly increased TBW (mean difference (MD) 1.73, 95% confidence interval (CI) 1.34-2.13, p < 0.00001), LBM (MD 1.06, 95% CI 0.30-1.81, p = 0.006), and QOL (standardized mean difference (SMD) 0.16, 95% CI 0.04-0.27, p = 0.006) compared with placebo without a significant difference in all AEs, severe AEs, OS, HGS or appetite. Anamorelin may be an effective treatment for CACS patients; however, further studies are needed to confirm the efficacy and safety of this drug.
Topics: Adult; Humans; Anorexia; Cachexia; Neoplasms; Administration, Oral
PubMed: 37709824
DOI: 10.1038/s41598-023-42446-x -
BMC Musculoskeletal Disorders Oct 2023Lateral ankle sprains are highly prevalent and result in tissue damage, impairments of muscle strength, instability, and muscle activation. Up to 74% will experience... (Meta-Analysis)
Meta-Analysis
The effect of movement representation techniques on ankle function and performance in persons with or without a lateral ankle sprain: a systematic review and meta-analysis.
BACKGROUND
Lateral ankle sprains are highly prevalent and result in tissue damage, impairments of muscle strength, instability, and muscle activation. Up to 74% will experience ongoing symptoms after a lateral ankle sprain. In healthy subjects, motor imagery might induce neural changes in the somatosensory and motor areas of the brain, yielding favourable enhancements in muscular force. However, during motor imagery, difficulties in building a motor image, no somatosensory feedback, and the absence of structural changes at the level of the muscle might explain the differences found between motor imagery and physical practice. In rehabilitation, motor imagery might be supportive in rebuilding motor networks or creating new networks to restore impairments in muscle activation and movement patterns. This systematic review was undertaken to summarize the current body of evidence about the effect on motor imagery, or action observation, on lower leg strength, muscle performance, ankle range of motion, balance, and edema in persons with, and without, a lateral ankle sprain compared to usual care, a placebo intervention, or no intervention.
METHODS
A systematic review with meta-analysis of randomized controlled trials was conducted in healthy participants and participants with a lateral ankle sprain. Motor imagery or action observation in isolation, or in combination with usual care were compared to a placebo intervention, or no intervention. An electronic search of MEDLINE, EMBASE, Cinahl, Psychinfo, Sportdiscus, Web of Science, Cochrane and Google Scholar was conducted, and articles published up to 7 June 2023 were included. Two reviewers individually screened titles and abstracts for relevancy using the inclusion criteria. Variables related to muscle strength, muscle function, range of motion, balance, return to sports tests, or questionnaires on self-reported function or activities were extracted. A risk of bias assessment was done using the Cochrane Risk-of-Bias tool II by two reviewers. Meta-analysis using a random effects model was performed when two or more studies reported the same outcome measures. The Standardized Mean Difference (SMD) was calculated over the change from baseline scores. Review manager 5.4 was used to perform analysis of subgroup differences and test for statistically significant differences. Confidence intervals were visually checked for overlap between subgroups.
RESULTS
Nine studies, six examining healthy participants and three examining participants with an acute lateral ankle sprain, were included. All studies were rated with moderate to high risk of bias overall. Quality of the motor imagery interventions differed largely between studies. Meta-analysis showed a large and significant effect of motor imagery on lower leg strength (SMD 1.47, 95% CI 0.44 to 2.50); however, the evidence was downgraded to very low certainty due to substantial heterogeneity (I = 73%), limitations in the studies (some concerns in risk of bias in all studies), and imprecision (n = < 300). Evidence showed no association with ankle range of motion (SMD 0.25, 95% CI -0.43 to 0.93), edema (SMD -1.11, 95% CI -1.60 to 3.81), the anterior reach direction of the Star Excursion Balance Test (SEBT) (SMD 0.73, 95% CI -0.62 to 2.08), the posterolateral direction (SMD 0.32, 95% CI -0.94 to 1.57), and the posteromedial direction (SMD 0.52, 95% CI -0.07 to 1.10). The certainty of evidence for the different comparisons was very low.
CONCLUSIONS
There is a low certainty, significant, positive effect for motor imagery being able to improve lower leg muscle strength in healthy participants. The effect on balance, range of motion and edema was uncertain and of very low certainty.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021243258.
Topics: Humans; Ankle; Lower Extremity; Ankle Joint; Ankle Injuries; Edema
PubMed: 37794344
DOI: 10.1186/s12891-023-06906-9 -
Frontiers in Pharmacology 2023Multiple immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatments for high-risk resected melanoma, with unclear...
Multiple immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatments for high-risk resected melanoma, with unclear comparative efficacy and safety. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 6 June 2023. We included RCTs that assess adjuvant ICIs or targeted therapies in high-risk resected melanoma. Frequentist random-effect network meta-analyses (NMA) were performed. The primary outcome was recurrence-free survival (RFS). Eleven trials including 10,712 patients and comparing 10 treatments (nivolumab [Nivo], ipilimumab 3 mg/kg [Ipi3], Ipi10, pembrolizumab [Pemb], vemurafenib [Vemu], bevacizumab [Beva], Nivo + Ipi1, Nivo + Ipi3, dabrafenib plus trametinib [Dab + Tram], and placebo/observation [Pla/Obs]) were included. NMA showed that all treatments showed RFS benefit over placebo/observation except Ipi3 (hazard ratio [HR], 0.78; 95% CI, 0.58-1.05). Combination therapy of Nivo + Ipi3 was the most effective treatment, which significantly improved RFS compared with other treatments. NMA also showed that all treatments were associated with an increased risk of grade 3-5 adverse events over placebo/observation except Nivo (HR, 1.25; 95% CI, 0.87-1.80). NMA suggested that Nivo and Pemb were the two safest treatments except for placebo/observation. Although three combination therapies ranked as the top three in terms of RFS, they did not show significant overall survival benefits compared to monotherapies including Pemb, Nivo, Ipi3, and Ipi10. In this NMA, adjuvant Nivo and Pemb are the preferred options in patients with resected melanoma considering the benefits and harms. Combination therapy of Nivo + Ipi3 may be a promising strategy, but more evidence from phase 3 trials is needed. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438667, PROSPERO (CRD42023438667).
PubMed: 38026956
DOI: 10.3389/fphar.2023.1284240 -
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