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Molecular Psychiatry Jan 2023A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.
Topics: Female; Humans; Adult; Depressive Disorder, Major; Duloxetine Hydrochloride; Sertraline; Citalopram; Venlafaxine Hydrochloride; Vortioxetine; Fluoxetine; Paroxetine; Mirtazapine; Amitriptyline; Desvenlafaxine Succinate; Fluvoxamine; Reboxetine; Network Meta-Analysis; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 36253442
DOI: 10.1038/s41380-022-01824-z -
The Cochrane Database of Systematic... May 2021Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.
OBJECTIVES
To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020.
SELECTION CRITERIA
Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs).
DATA COLLECTION AND ANALYSIS
Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results.
MAIN RESULTS
Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants.
AUTHORS' CONCLUSIONS
Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.
Topics: Adolescent; Antidepressive Agents; Bias; Child; Citalopram; Depressive Disorder, Major; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Female; Fluoxetine; Humans; Male; Mirtazapine; Network Meta-Analysis; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Suicidal Ideation; Venlafaxine Hydrochloride; Vilazodone Hydrochloride; Vortioxetine
PubMed: 34029378
DOI: 10.1002/14651858.CD013674.pub2 -
International Braz J Urol : Official... 2023bladder based on a systematic review and network meta-analysis approach. (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
bladder based on a systematic review and network meta-analysis approach.
METHODS
Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software.
RESULT
A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache.
CONCLUSION
Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.
Topics: Humans; Urinary Bladder, Overactive; Solifenacin Succinate; Tolterodine Tartrate; Network Meta-Analysis; Double-Blind Method; Constipation; Xerostomia; Treatment Outcome; Muscarinic Antagonists; Randomized Controlled Trials as Topic
PubMed: 37506033
DOI: 10.1590/S1677-5538.IBJU.2023.0158 -
Menopause (New York, N.Y.) Jan 2024The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared... (Meta-Analysis)
Meta-Analysis
Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause.
IMPORTANCE
The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown.
OBJECTIVE
We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women.
EVIDENCE REVIEW
Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models.
FINDINGS
The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from higher desvenlafaxine doses or gabapentin ER 1800 mg. For ≥75% responder rates, fezolinetant 45 mg was less effective than tibolone 2.5 mg (not available in the United States) and conjugated estrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the United States), did not differ significantly from other non-HT regimens studied and was superior to desvenlafaxine 50 mg and placebo.
CONCLUSIONS
The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS.
RELEVANCE
These findings may inform decision making with regard to the individualized management of bothersome VMS due to menopause.
Topics: Female; Humans; Hot Flashes; Desvenlafaxine Succinate; Network Meta-Analysis; Gabapentin; Bayes Theorem; Menopause; Estrogens, Conjugated (USP)
PubMed: 38016166
DOI: 10.1097/GME.0000000000002281 -
Nutrients Nov 2023Multiple studies have indicated that distinct metabolites are involved in the occurrence and development of osteopenia (ON) and osteoporosis (OP); however, these... (Meta-Analysis)
Meta-Analysis Review
Multiple studies have indicated that distinct metabolites are involved in the occurrence and development of osteopenia (ON) and osteoporosis (OP); however, these metabolites in OP and ON have not yet been classified and standardized. This systematic review and meta-analysis included 21 articles aiming to investigate the distinct metabolites in patients with ON and OP. The quality of the included articles was generally high; seventeen studies had >7 stars, and the remaining four received 6 stars. This systematic review showed that three metabolites (phosphatidylcholine (PC) (lipid metabolites), galactose (carbohydrate metabolites), and succinic acid (other metabolites)) increased, four (glycylglycine (gly-gly), cystine (amino acids), sphingomyelin (SM) (lipid metabolites) and glucose (carbohydrate metabolites)) decreased, and five (glutamine, hydroxyproline, taurine (amino acids), lysophosphatidylcholine (LPC) (lipid metabolites), and lactate (other metabolites)) had conflicting directions in OP/ON. The results of the meta-analysis show that gly-gly (MD = -0.77, 95%CI -1.43 to -0.11, = 0.02) and cystine (MD = -5.52, 95%CI -7.35 to -3.68, < 0.00001) decreased in the OP group compared with the healthy control group. Moreover, LPC (MD = 1.48, 95%CI 0.11 to 2.86, = 0.03) increased in the OP group compared with the healthy control group. These results indicate that distinct metabolites were associated with ON and OP, which could be considered a predictor for OP.
Topics: Humans; Cystine; Osteoporosis; Bone Diseases, Metabolic; Amino Acids; Lysophosphatidylcholines; Carbohydrates
PubMed: 38068753
DOI: 10.3390/nu15234895 -
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 -
Frontiers in Microbiology 2022Spondyloarthritis (SpA) is a group of rheumatic diseases that cause joint inflammation. Accumulating studies have focused on the metabolomic profiling of SpA in recent... (Review)
Review
Spondyloarthritis (SpA) is a group of rheumatic diseases that cause joint inflammation. Accumulating studies have focused on the metabolomic profiling of SpA in recent years. We conducted a systematic review to provide a collective summary of previous findings on metabolomic profiling associated with SpA. We systematically searched PubMed, Medline, Embase and Web of Science for studies on comparisons of the metabolomic analysis of SpA patients and non-SpA controls. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included articles. From 482 records identified, 31 studies were included in the analysis. A number of metabolites were differentially distributed between SpA and non-SpA cases. SpA patients showed higher levels of glucose, succinic acid, malic acid and lactate in carbohydrate metabolism, higher glycerol levels and lower fatty acid (especially unsaturated fatty acid) levels in lipid metabolism, and lower levels of tryptophan and glutamine in amino acid metabolism than healthy controls. Both conventional and biological therapy of SpA can insufficiently reverse the aberrant metabolism state toward that of the controls. However, the differences in the results of metabolic profiling between patients with SpA and other inflammatory diseases as well as among patients with several subtypes of SpA are inconsistent across studies. Studies on metabolomics have provided insights into etiological factors and biomarkers for SpA. Supplementation with the metabolites that exhibit decreased levels, such as short-chain fatty acids (SCFAs), has good treatment prospects for modulating immunity. Further studies are needed to elucidate the role of disordered metabolic molecules in the pathogenesis of SpA.
PubMed: 36118235
DOI: 10.3389/fmicb.2022.965709 -
The Journal of Urology Nov 2023Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms and discomfort. Prior studies have examined the effects of various medication regimens on ureteral stent symptoms. This study utilized Bayesian network meta-analysis to analyze all available evidence on the pharmacological management of ureteral stent-related symptoms.
MATERIALS AND METHODS
In December 2022 a systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines on randomized prospective studies on pharmacological management of ureteral stent-related symptoms reporting outcomes using the Ureteral Stent Symptom Questionnaire score on urinary symptoms and pain. The data were analyzed in Review Manager 5.3 and R Studio where a Bayesian network meta-analysis was performed. Treatments were ranked using surface under the cumulative ranking curve and mean difference vs placebo with 95% credible intervals.
RESULTS
A total of 26 studies were analyzed. These were used to build networks which were modeled to run 100,000 Markov Chain Montecarlo simulations each. Drug-class analysis revealed the most effective class for each domain: for urinary symptoms, sexual performance, general health, and work performance-combined α-blocker and anticholinergic and phosphodiesterase 5 inhibitors; for pain-combined anticholinergic and pregabalin. The following were the most effective drugs and dosages for specific symptoms: for urinary symptoms-combined silodosin 8 mg+solifenacin 10 mg; for pain-combined silodosin 8 mg+solifenacin 10 mg; for sexual performance-tadalafil 5 mg. Combined silodosin 8 mg+solifenacin 10 mg+tadalafil 5 mg has the best general health scores while solifenacin 10 mg had the best work experience scores.
CONCLUSIONS
This network meta-analysis demonstrated that the most effective drug therapy is different for each symptom domain. It is important to consider a patient's chief complaint and domains in order to ascertain the optimal medication regimen for each patient. Further iterations of this analysis can be strengthened by trials that directly compare more of these drugs instead of relying on indirect evidence.
Topics: Humans; Solifenacin Succinate; Tadalafil; Network Meta-Analysis; Prospective Studies; Bayes Theorem; Quality of Life; Ureter; Pain; Cholinergic Antagonists; Stents
PubMed: 37428119
DOI: 10.1097/JU.0000000000003616 -
The Cochrane Database of Systematic... Nov 2021Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial... (Review)
Review
BACKGROUND
Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis.
OBJECTIVES
To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis.
MAIN RESULTS
We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events).
AUTHORS' CONCLUSIONS
Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
Topics: Acetaminophen; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Hearing Loss; Humans; Meningitis, Bacterial
PubMed: 34813078
DOI: 10.1002/14651858.CD013437.pub2 -
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