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Neuroradiology May 2019Grading of brain gliomas is of clinical importance, and noninvasive molecular imaging may help differentiate low- and high-grade gliomas. We aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Grading of brain gliomas is of clinical importance, and noninvasive molecular imaging may help differentiate low- and high-grade gliomas. We aimed to evaluate the diagnostic performance of amide proton transfer-weighted (APTw) MRI for differentiating low- and high-grade gliomas on 3-T scanners.
METHODS
A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to March 28, 2018. Original articles evaluating the diagnostic performance of APTw MRI for differentiating low- and high-grade gliomas were selected. The pooled sensitivity and specificity were calculated using a bivariate random-effects model. A coupled forest plot and a hierarchical summary receiver operating characteristic curve were obtained. Heterogeneity was investigated using Higgins inconsistency index (I) test. Meta-regression was performed.
RESULTS
Ten original articles with a total of 353 patients were included. High-grade gliomas showed significantly higher APT signal intensity than low-grade gliomas. The pooled sensitivity and specificity for the diagnostic performance of APTw MRI for differentiating low-grade and high-grade gliomas were 88% (95% CI, 77-94%) and 91% (95% CI, 82-96%), respectively. Higgins I statistic demonstrated heterogeneity in the sensitivity (I = 68.17%), whereas no heterogeneity was noted in the specificity (I = 44.84%). In meta-regression, RF saturation power was associated with study heterogeneity. Correlation coefficients between APT signal intensity and Ki-67 cellular proliferation index ranged from 0.430 to 0.597, indicating moderate correlation. All studies showed excellent interobserver agreement.
CONCLUSIONS
Although heterogeneous protocols were used, APTw MRI demonstrated excellent diagnostic performance for differentiating low- and high-grade gliomas. APTw MRI could be a reliable technique for glioma grading in clinical practice.
Topics: Amides; Brain Neoplasms; Diagnosis, Differential; Glioma; Humans; Magnetic Resonance Imaging; Neoplasm Grading; Sensitivity and Specificity
PubMed: 30666352
DOI: 10.1007/s00234-018-02152-2 -
Journal of Clinical Pharmacy and... Aug 2018Migraine is a common and costly neurological disorder that affects approximately 1 of every 7 people annually. Pharmacological therapy for prevention of migraine is... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Migraine is a common and costly neurological disorder that affects approximately 1 of every 7 people annually. Pharmacological therapy for prevention of migraine is warranted when patients experience at least 6 headache days, 4 headache days with at least some impairment or 3 headache days with severe impairment or requiring bed rest in a month. Levetiracetam is an antiepileptic drug that has the potential to be beneficial for migraine prophylaxis. The objective of this review was to assess the safety and efficacy of levetiracetam for migraine prophylaxis.
METHODS
A systematic search was conducted in MEDLINE (1946-August 2017), EMBASE (1947-August 2017) and CENTRAL using the terms: migraine disorders, migraine, or headache and etiracetam or levetiracetam. Animal studies, case reports, abstracts, letters to the editor and those not written in English were excluded.
RESULTS AND DISCUSSION
Eleven articles were identified for inclusion. Of the studies included, 2 were retrospective chart reviews, 4 were randomized placebo- or active comparator-controlled trials, and the remaining 5 were prospective, open-label studies. All studies found a statistically significant decrease in headache frequency per month compared to baseline or placebo when used for treatment of episodic migraine (2.96-10.9 headache/mo decrease), and 57.9%-100% of patients had at least a 50% decrease in headache frequency from baseline. Significance was not consistently demonstrated in the prophylactic treatment of chronic migraine. The most common adverse effects noted included somnolence, dizziness and behavioural effects but generally did not require discontinuation.
WHAT IS NEW AND CONCLUSION
The studies included in this review indicate that levetiracetam is well-tolerated and may be an alternative treatment option for episodic migraine prophylaxis. Additional clinical evidence is necessary to establish the efficacy of levetiracetam for the prophylactic treatment of chronic migraine.
Topics: Animals; Anticonvulsants; Humans; Levetiracetam; Migraine Disorders; Piracetam; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 29781197
DOI: 10.1111/jcpt.12715 -
Nature Communications Sep 2021Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from... (Meta-Analysis)
Meta-Analysis
Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.
Topics: Amides; Anticholesteremic Agents; Benzodiazepines; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Coronary Disease; Esters; Humans; Mendelian Randomization Analysis; Oxazolidinones; Quinolines; Sulfhydryl Compounds
PubMed: 34561430
DOI: 10.1038/s41467-021-25703-3 -
International Journal of Hematology Dec 2017Hemoglobin E-beta thalassemia (Hb E/β-thalassemia) is a distinct, yet common, type of β-thalassemia, in which the patient co-inherits a β-thalassemia allele from one... (Meta-Analysis)
Meta-Analysis Review
Hemoglobin E-beta thalassemia (Hb E/β-thalassemia) is a distinct, yet common, type of β-thalassemia, in which the patient co-inherits a β-thalassemia allele from one parent, and a structural variant, Hb E, from the other parent. This co-inheritance leads to remarkable clinical heterogeneity, varying degrees of chronic anemia, and a wide spectrum of complications due to ineffective erythropoiesis and iron overload. Hydroxyurea (HU), an oral chemotherapeutic drug, is expected to decrease disease severity. To assess the clinical efficacy and safety of HU in Hb E/β-thalassemia patients. We searched MEDLINE, EMBASE, Cochrane databases, and major preceding conferences for studies that assessed HU in Hb E/β-thalassemias patients. The effect size was estimated as a proportion (responder/sample size). Qualities of eligible studies were assessed using NIH tools. A total of five [one randomized clinical trial (RCT) and four observational] studies involving 106 patients were included. HU was associated with a significant RR of 46% with no statistical heterogeneity. No serious adverse effects were reported. Patients with Hb E/β-thalassemia may benefit from a trial of HU, though large RCTs assessing efficacy should be conducted to confirm the findings of this meta-analysis and to assess long-term toxicity and response sustainability.
Topics: Hemoglobin E; Humans; Hydroxyurea; Randomized Controlled Trials as Topic; beta-Thalassemia
PubMed: 28786080
DOI: 10.1007/s12185-017-2307-0 -
International Journal of... 2023Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium... (Review)
Review
Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
Topics: Humans; beta-Lactamase Inhibitors; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium tuberculosis; Carbapenems; Penicillins; Clavulanic Acid; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous
PubMed: 37721224
DOI: 10.4103/ijmy.ijmy_131_23 -
Hematology/oncology and Stem Cell... Sep 2017Nontransfusion-dependent β-thalassemia (NTDβT) syndromes consist of β-thalassemia intermedia and moderate hemoglobin E/β thalassemias. They are characterized by... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE/BACKGROUND
Nontransfusion-dependent β-thalassemia (NTDβT) syndromes consist of β-thalassemia intermedia and moderate hemoglobin E/β thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea (HU), an oral chemotherapeutic drug, is anticipated to decrease disease severity.
METHODS
We performed a meta-analysis to evaluate the clinical efficacy and safety of HU in NTDβT patients of any age. MEDLINE, EMBASE, Cochrane databases, and major conference proceedings for studies that assessed HU in NTDβT patients were searched. Qualities of eligible studies were assessed by National Institutes of Health tools.
RESULTS
Seventeen studies, collectively involving 709 patients, fulfilled the eligibility criteria. HU was associated with a significant decrease in transfusion need in severe NTDβT with complete and overall (≥50%) response rates of 42% and 79%, respectively. For mild NTDβT, HU was effective in raising hemoglobin by 1g/L in 64% of patients.
CONCLUSION
HU appears to be effective, well tolerated, and associated with mild and transient adverse events. NTDβT patients may benefit from a trial of HU, although large randomized clinical trials assessing its efficacy should be conducted to confirm the findings of this meta-analysis and to assess its long-term toxicity and response sustainability.
Topics: Adolescent; Adult; Blood Transfusion; Child; Child, Preschool; Humans; Hydroxyurea; Middle Aged; Young Adult; beta-Thalassemia
PubMed: 28408107
DOI: 10.1016/j.hemonc.2017.02.002 -
Clinical Therapeutics May 2023Ranolazine is used to treat stable angina pectoris, the most common symptom of ischemic heart disease. Appropriate management of chronic stable angina pectoris is... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ranolazine is used to treat stable angina pectoris, the most common symptom of ischemic heart disease. Appropriate management of chronic stable angina pectoris is essential from both a clinical and an economic view point.
METHODS
This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included cost-utility analyses, which compared ranolazine with other standard treatments for treating stable angina pectoris. The search was conducted in PubMed, EMBASE, and Scopus databases. A random-effects model based on the DerSimonian and Laird method was used to pool the incremental net benefit reported in purchasing power parity adjusted US dollars. The modified economic evaluation checklist was used to assess the risk of bias.
FINDINGS
The pooled results from 7 selected studies with a time horizon of 1 year show that add-on ranolazine was significantly cost-effective compared with standard treatment, with a pooled incremental net benefit of US$1335 (95% CI, 500 to 2169) but with substantial heterogeneity (I = 79.46%). On subgroup analysis, ranolazine was cost-effective from the payers' perspective (US$1975; 95% CI, 1042 to 2908; I = 69.23) but not from a societal perspective (US$297; 95% CI, -241 to 715; I = 0%)]. There was limited evidence from lower economies.
IMPLICATIONS
Pooled evidence suggests that add-on ranolazine therapy is cost-effective for chronic stable angina pectoris up to a 1-year time horizon. There is a lacuna of evidence from low- and middle-income countries and on long-term cost-effectiveness. The current evidence synthesis may provide a macroeconomic point of view for policy makers regarding the direction of ranolazine's cost-effectiveness for evidence-informed policy-making. PROSPERO identifier: CRD42022332454.
Topics: Humans; Ranolazine; Angina, Stable; Myocardial Ischemia; Cost-Benefit Analysis; Acetanilides
PubMed: 37087299
DOI: 10.1016/j.clinthera.2023.04.004 -
Journal of Global Antimicrobial... Jun 2022The aim of this study was to determine the pooled estimate of Staphylococcus aureus and coagulase negative staphylococci and their antimicrobial-resistance in patients... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of this study was to determine the pooled estimate of Staphylococcus aureus and coagulase negative staphylococci and their antimicrobial-resistance in patients with wound infection.
METHODS
Literature searches were carried out in the electronic biomedical databases and indexing services such as PubMed/MEDLINE, EMBASE, Science Direct, Web of Science and Google Scholar. Original records of research articles, available online from 1988 to March 2020, addressing the rates and antimicrobial-resistance pattern of staphylococcus aureus (S. aureus) and coagulase negative staphylococci (CoNS) in patients with wound infection were identified and screened. Endnote citation manager software version X9 for windows was utilized to collect and organize search outcomes and for removal of duplicate articles. The relevant data were extracted from included studies using a format prepared in Microsoft Excel and exported to STATA 14.0 software for the outcome measures analyses and subgrouping.
RESULTS
The electronic databases search yielded 378 studies, of which 39 met predefined inclusion criteria and included in the final analyses. The pooled estimate of wound infection was 36% [95% CI: 23-50%) for S. aureus and 12% [95% CI: 9-14%) for CoNS. S. aureus exhibited a higher rate of resistance to penicillin (84%), ampicillin (83%), amoxicillin (67%), methicillin (50%), cotrimoxazole (50%), tetracycline (61%), doxycycline (58%), chloramphenicol (49%) and erythromycin (45%). However, relative lower resistant rate was observed to Augmentin (amoxicillin-clavulanic acid) (35%), gentamicin (33%), norfloxacin (23%), ciprofloxacin (26%), ceftriaxone (36%), vancomycin (29%) and clindamycin (40%). Similarly, for CoNS there was high resistance to methicillin, 52% [95% CI: 26-78%]) and other antibiotics, but lower resistance to clindamycin, 15% [95% CI: 6-24]) and vancomycin, 22% [95% CI: 2-41%]). Ceftriaxone resistance was observed with prevalence of 36% [95% CI: 21-50%] for S. aureus and 42% [95% CI: 29-55%] for CoNS.
CONCLUSION
There was high resistance of staphylococci bacterial species to commonly used antimicrobials in the clinical settings in Ethiopia. It is a high time to implement multitude strategies to contain the threat. Further research focusing on factors promoting resistance and the effect of resistance on treatment outcome studies on these virulent organisms are warranted.
Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Clindamycin; Coagulase; Ethiopia; Humans; Methicillin; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Vancomycin; Wound Infection
PubMed: 34801740
DOI: 10.1016/j.jgar.2021.10.025 -
Saudi Journal of Gastroenterology :... 2023Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a meta-analysis to assess the effect of this therapy for H. pylori eradication.
METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science database from inception until November 2022, collecting randomized controlled trials (RCTs) comparing VA dual therapy with other regimens for H. pylori eradication. Pooled relative risks (RRs) were calculated using random effects model.
RESULTS
Five RCTs were ultimately included. Compared with the vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy, the eradication rate of VA dual therapy was lower in intention-to-treat (ITT) analysis (n = 3 RCTs, RR = 0.94, 95% CI: 0.88-0.99, P = 0.03), but there was no significant difference between them in the per-protocol (PP) analysis (RR = 0.96, 95% CI: 0.91-1.01, P = 0.11). For clarithromycin-resistant H. pylori strains, the eradication rate of VA dual therapy was significantly higher than that of the VAC triple therapy (n = 2 RCTs, RR = 1.20, 95% CI: 1.03-1.39, P = 0.02). Compared with the PPI-based triple therapy (PAC), VA dual therapy had a superior eradication rate (n = 2 RCTs, ITT analysis: RR = 1.13, 95% CI: 1.04-1.23, P = 0.003; PP analysis: pooled RR = 1.14, 95% CI: 1.06-1.22, P = 0.0004). Compared with VAC or PAC triple therapy, VA dual therapy has a similar incidence of total adverse events and compliance.
CONCLUSIONS
VA dual therapy had a similar effect compared to VAC triple therapy and was superior to PAC triple therapy. Future RCTs are needed to ascertain the optimal dosage and duration of vonoprazan and amoxicillin, and the effect of VA dual therapy compared with the mainstream regimens recommended by current guidelines.
Topics: Humans; Amoxicillin; Clarithromycin; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Treatment Outcome
PubMed: 37602635
DOI: 10.4103/sjg.sjg_153_23 -
International Journal of Clinical... Oct 2017Lozenges containing Amylmetacresol and 2,4-Dichlorobenzylalcohol (AMC/DCBA, eg Strepsils ) are marketed as a remedy for acute sore throat. This over-the-counter... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lozenges containing Amylmetacresol and 2,4-Dichlorobenzylalcohol (AMC/DCBA, eg Strepsils ) are marketed as a remedy for acute sore throat. This over-the-counter formulation has antiseptic and local anaesthetic qualities.
OBJECTIVES
The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of AMC/DCBA for the relief of pain associated with acute uncomplicated sore throat.
METHODS
A systematic review of Literature was conducted using databases Medline, Embase and Cochrane to identify randomised controlled trials comparing AMC/DCBA against placebo or alternative local treatment options for acute uncomplicated sore throat. An additional hand search was performed. Two reviewers independently assessed citations for relevance, inclusion criteria and risk of bias. Meta-analysis was performed on included trials and standardised mean differences (SMD; d ) with 95% confidence intervals (CIs) were calculated.
RESULTS
The literature search yielded 77 citations, 3 of which met the inclusion criteria. AMC/DCBA lozenges (0.6 mg Amylmetacresol, 1.2 mg 2, 4-Dichlorobenzylalcohol) were compared with unflavoured, non-medicated lozenges. The AMC/DCBA formulation additionally contained lidocaine in one and flavouring additives in another trial. A total of 660 adults participated in the included trials. Primary outcome was reduction in pain intensity against baseline, 2 hours after intervention compared with placebo group. Fixed effects meta-analysis resulted in a standardised mean difference in pain intensity of -0.6 (-0.75; -0.45) on an 11-point ordinal rating scale, favouring the AMC/DCBA lozenges. Secondary outcomes were sore throat relief, difficulty swallowing and throat numbness. No serious side effects were reported, whereas mild side effects like headache, cough, nasal congestion and irritation of the oral cavity, were reported in up to 16% of subjects in both groups. All included trials were sponsored by a manufacturer of AMC/DCBA containing lozenges.
CONCLUSIONS
Lozenges with AMC/DCBA can be a safe treatment option to relieve pain in patients with uncomplicated sore throat looking for local treatment options and valuing the modest additional effect compared with non-medicated lozenges. Registration: PROSPERO CRD42015008826.
Topics: Administration, Oral; Humans; Lidocaine; Pharyngitis
PubMed: 28869700
DOI: 10.1111/ijcp.13002