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JAMA Pediatrics Mar 2013OBJECTIVES To conduct a systematic review and analysis of trial data submitted to the US Food and Drug Administration (FDA) to identify possible causes for the failure... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES To conduct a systematic review and analysis of trial data submitted to the US Food and Drug Administration (FDA) to identify possible causes for the failure of pediatric trials of triptans for treatment of migraines. DATA SOURCE The FDA website for drug information and published literature. STUDY SELECTION All pediatric efficacy and pharmacokinetics trial data of drugs used for abortive treatment of migraine submitted to the FDA from January 1, 1999, through December 31, 2011. MAIN OUTCOME MEASURES Patient demographic baseline characteristics, inclusion and exclusion criteria, trial designs, efficacy end points, and pharmacokinetic profiles were analyzed and compared across drug products. RESULTS We analyzed data for sumatriptan succinate nasal spray and zolmitriptan, eletriptan hydrobromide, almotriptan malate, and rizatriptan benzoate tablets. Seven efficacy trials had a randomized, double-blinded, placebo-controlled, parallel-group trial design. In 4 trials, patients were required to have a history of migraine attacks lasting at least 4 hours. High response rates for placebo were observed in all trials, with pain relief at 2 hours ranging from 53% to 57.5%. Nonrandomization of patients with an early placebo response design was used in the rizatriptan trial in 2011. Compared with the rizatriptan trial conducted in 1999, the 2011 rizatriptan trial reduced the placebo response rate by 6% for headache freedom at the 2-hour posttreatment end point owing to study design. The pharmacokinetic profiles between adolescents and adults were statistically similar. CONCLUSIONS High placebo response rates are consistent across all trials and may represent the principal challenge in pediatric trials of drugs for abortive treatment of migraine. Enrichment with selection of subjects with long-lasting migraine attacks is not sufficient to overcome high placebo response rates. Another enrichment strategy, the nonrandomization of patients with an early placebo response, successfully reduces the high placebo response rate for rizatriptan and is a trial design that should be considered for future pediatric trials of abortive migraine therapeutics.
Topics: Adolescent; Humans; Migraine Disorders; Placebo Effect; Randomized Controlled Trials as Topic; Research Design; Tryptamines; United States; United States Food and Drug Administration
PubMed: 23359002
DOI: 10.1001/jamapediatrics.2013.872 -
International Urology and Nephrology Mar 2015We carried out a systematic review and meta-analysis to assess the efficacy and safety of imidafenacin for treating overactive bladder in adult. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We carried out a systematic review and meta-analysis to assess the efficacy and safety of imidafenacin for treating overactive bladder in adult.
METHODS
A literature review was performed to identify all published randomized placebo-controlled trials of imidafenacin for the treatment of OAB. The search included the following databases: MEDLINE, EMBASE. The reference lists of retrieved studies were also investigated.
RESULTS
Five publications involving a total of 1,428 patients were used in the analysis, which compared imidafenacin with propiverine and solifenacin. We found that imidafenacin was effective in treating OAB in our meta-analysis, which was similar to propiverine in its efficacy. The mean number of UI per week (the standardized mean difference (SMD) = 1.23, 95% CI -0.19 to 2.65, p = 0.09), the mean number of urgency episodes per day (SMD = 0.26, 95% CI -0.11 to 0.63, p = 0.17), the mean number of micturitions per day (SMD = 0.01, 95% CI -0.30 to 0.31, p = 0.96), and the mean urine volume (ml) per micturition (SMD = -13.04, 95% CI -20.45 to -5.62, p = 0.0006) indicated that imidafenacin was similar to propiverine in its efficacy. Mean OABSS (SMD = 0.48, 95% CI -0.08 to 1.03, p = 0.09) indicated that imidafenacin was also similar to solifenacin in its efficacy. Besides, imidafenacin was better tolerated than propiverine in the safety, indicated by dry mouth (OR 0.73, 95% CI 0.54-0.98, p = 0.04) and any adverse events (OR 0.63, 95% CI 0.46-0.88, p = 0.006). Moreover, imidafenacin was also better tolerated than solifenacin in the safety, indicated by constipation (OR 0.21, 95% CI 0.08-0.53, p = 0.001) and any adverse events (OR 0.33, 95% CI 0.15-0.71, p = 0.004).
CONCLUSIONS
This meta-analysis indicates that imidafenacin was similar to propiverine or solifenacin in its efficacy for OAB and was better tolerated than propiverine or solifenacin in the safety for OAB. We conclude that imidafenacin is preferable to propiverine or solifenacin from a perspective of safety.
Topics: Adult; Benzilates; Constipation; Humans; Imidazoles; Randomized Controlled Trials as Topic; Solifenacin Succinate; Urinary Bladder, Overactive; Urological Agents; Xerostomia
PubMed: 25636812
DOI: 10.1007/s11255-015-0916-1 -
Pharmacopsychiatry Sep 2015Desvenlafaxine, the active metabolite of venlafaxine, was approved in 2008 by the FDA for the treatment of depression. The aim of the present review is to provide an... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Desvenlafaxine, the active metabolite of venlafaxine, was approved in 2008 by the FDA for the treatment of depression. The aim of the present review is to provide an overview of the existing trials with desvenlafaxine and assess its overall efficacy and tolerability.
METHODS
We searched in PubMed, EMBASE and the Cochrane Library for eligible studies (double-blind randomized control trials). A random effects model was used for the estimation of effect sizes.
RESULTS
17 trials were found in total. In the placebo-controlled trials the overall risk ratio for response was 1.24 (1.16-1.32, p<0.001), for remission 1.29 (1.16-1.43, p<0.001), for dropouts 1.16 (0.99-1.35, p=0.066) and for dropouts due to adverse events 1.98 (1.45-2.69, p<0.001). There were no differences between the various doses that were used (i. e., 50 mg, 100 mg, 200 mg, 400 mg). The mean risk ratio for response in the head-to-head trials was 0.90 (0.82-0.98, p=0.014) and for remission 0.82 (0.71-0.95, p=0.009).
DISCUSSION
The risk ratios for response and remission were moderate. We further provide some evidence that desvenlafaxine might not be as efficacious as other antidepressants.
Topics: Antidepressive Agents; Depression; Desvenlafaxine Succinate; Humans
PubMed: 26205685
DOI: 10.1055/s-0035-1555879 -
Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
METHODS
Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
RESULTS
High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
CONCLUSION
VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
Journal of Traditional Chinese Medicine... Oct 2016To assess the effect and safety of Shengxuening (SXN), extract from excrement of bombyxin, in the treatment of renal anemia, compared to ferrous succinate and ferrous... (Review)
Review
OBJECTIVE
To assess the effect and safety of Shengxuening (SXN), extract from excrement of bombyxin, in the treatment of renal anemia, compared to ferrous succinate and ferrous sulfate.
METHODS
According to the participant, intervention, comparison, outcomes, study design (PICOS) principles, we searched the Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Chinese Evidence-Based Medicine Database, Wanfang Database (From establishment to December 2014). Two reviewers selected articles independently according to the inclusion and exclusion criteria. The quality of included studies was assessed by using the Cochrane Handbook. All statistical analyses were conducted by using Revman (vision 5.2) software.
RESULTS
A total of 14 randomized controlled trials (RCTs) were enrolled in the review. The results revealed that, when compared with blank group, SXN significantly improved the hemoglobin (P >) levels [MD = 6.29, 95% CI (1.65-10.94), P < 0.0008] and albumin (ALB) [MD = 10.98, 95% CI (6.97-14.99), P < 0.00001]. In addition, SXN could significantly increase the P > levels [MD = 10.98, 95% CI (6.97, 14.99), P < 0.00001]. Compared with other oral medicine SXN could improve the P > levels effectively [MD = 8.49, 95% CI (2.40, 14.58), P = 0.006]. And the subgroups analysis shown that compared with ferrous-sulfate there were significant differences [MD = 17.4, 95% CI (15.06, 19.73), P < 0.000 01] and the result of ferrous-succinate had significant differences [MD = 5.34, 95% CI (2.12, 8.56), P = 0.001] too. Compared with Intravenous iron groups, there were statistical differences [MD = - 5.04, 95% CI (- 9.59, - 0.50), P = 0.03]. In the safety analysis, the rate of adverse reactions in SXN groups and control groups were 19.3% and 3.7%, respectively (P < 0.000 01). Due to our studies were of poor methodological quality, and the sample size were small, the results were influenced by bias.
CONCLUSION
Our findings suggest that the SXN had better effect and was safer in the treatment of RA than ferrous succinate and ferrous sulfate.
Topics: Anemia; Animals; Bombyx; China; Drugs, Chinese Herbal; Humans; Neuropeptides; Randomized Controlled Trials as Topic
PubMed: 29932629
DOI: 10.1016/s0254-6272(16)30077-2 -
Head & Neck Jul 2024Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs.
METHODS
Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochran's Q test and I test assessed heterogeneity. Funnel plot and Egger's regression test assessed publication bias.
RESULTS
Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations.
CONCLUSION
Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.
Topics: Humans; Succinate Dehydrogenase; Head and Neck Neoplasms; Paraganglioma; Mutation; Female; Male
PubMed: 38273766
DOI: 10.1002/hed.27652 -
American Journal of Therapeutics 2020Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF)...
BACKGROUND
Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF) and atrial fibrillation (AF). Among different beta-blockers, metoprolol is a selective beta1-adrenergic antagonist, which has been extensively used since the 1970s.
AREAS OF UNCERTAINTY
Although current guidelines include recommendations for the use of controlled-release metoprolol succinate in specific HF and AF indications, and despite extensive clinical experience with metoprolol, comparative evidence on the use of metoprolol succinate compared with other beta-blockers in these indications is limited.
DATA SOURCES
We systematically reviewed the data from head-to-head studies directly comparing this compound with other beta-blockers in the treatment of HF or AF. Only clinical trials and observational studies were considered; no other limits were applied. The quality and relevance of retrieved articles were reviewed.
RESULTS
A total of 18 articles of the 353 articles identified were selected for inclusion; 12 HF articles and 6 for AF. Additional references were identified from the bibliographies of retrieved articles. The studies show that oral prophylaxis with an appropriate dose of metoprolol may reduce new incidents of AF in high-risk patients. Furthermore, metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF.
CONCLUSIONS
Despite the introduction of newer beta-blockers with differing clinical characteristics since its introduction, metoprolol succinate remains a useful drug in both HF and AF.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-Antagonists; Atrial Fibrillation; Heart Failure; Humans; Metoprolol
PubMed: 31385823
DOI: 10.1097/MJT.0000000000001043 -
Journal of Medical Genetics Dec 2012The main objective of this study was to perform a systematic review and meta-analysis on the risk of developing malignant paraganglioma (PGL) in SDHB-mutation and... (Meta-Analysis)
Meta-Analysis Review
The main objective of this study was to perform a systematic review and meta-analysis on the risk of developing malignant paraganglioma (PGL) in SDHB-mutation and SDHD-mutation carriers. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier (2000-August 2011) and references of key articles were searched to identify potentially relevant studies. The main outcomes were the pooled incidence and prevalence of malignant PGL in SDHB-mutation and SDHD-mutation carriers. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Twelve studies were included. The pooled incidence of malignant PGL in populations comprising both asymptomatic mutation carriers and mutation carriers with manifest non-malignant PGL was 17% (95% CI 10 to 28) for SDHB-mutation carriers and 8% (95% CI 2 to 26) for SDHD-mutation carriers. The pooled risk in prevalence studies was 13% (95% CI 4 to 34) and 4% (95% CI 2 to 7), respectively. In studies comprising only mutation carriers with manifest disease, the pooled prevalence was 23% (95% CI 16 to 33) for SDHB-mutation and 3% (95% CI 1 to 10) for SDHD-mutation carriers. Incidence and prevalence of malignant PGL are higher in SDHB-mutation than in SDHD-mutation carriers, but lower in SDHB-mutation carriers than hitherto appreciated.
Topics: Genetic Predisposition to Disease; Genotype; Humans; Incidence; Mutation; Paraganglioma; Prevalence; Risk; Succinate Dehydrogenase
PubMed: 23099648
DOI: 10.1136/jmedgenet-2012-101192 -
Frontiers in Molecular Biosciences 2023Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
PubMed: 37614441
DOI: 10.3389/fmolb.2023.1215039 -
European Urology Focus Jul 2022The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging.
OBJECTIVE
The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB.
EVIDENCE ACQUISITION
A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately.
EVIDENCE SYNTHESIS
Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events.
CONCLUSIONS
Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events.
PATIENT SUMMARY
This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.
Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Network Meta-Analysis; Receptors, Adrenergic; Solifenacin Succinate; Urinary Bladder, Overactive; Urinary Incontinence
PubMed: 34563481
DOI: 10.1016/j.euf.2021.08.011