Amlodipine as adjuvant therapy to current chelating agents for reducing iron overload in thalassaemia major: a systematic review, meta-analysis and simulation of future studies.

BACKGROUND AND OBJECTIVES: Iron overload in thalassaemia is a crucial prognostic factor and a major cause of death due to heart failure or arrhythmia. Therefore, previous research has recommended amlodipine as an auxiliary treatment to current chelating agents for reducing iron overload in thalassaemia patients. MATERIALS AND METHODS: A systematic review and meta-analysis of the results of three randomized clinical trials evaluating the use of amlodipine in thalassaemia patients through 12 databases were carried out. RESULTS: Our final cohort included 130 patients. Insignificant difference in decreasing liver iron concentrations was found between amlodipine and control groups {weighted mean difference = -0·2, [95% confidence interval = (-0·55-0·15), P = 0·26]}. As regards serum ferritin, our analysis also showed no significant difference in serum ferritin between amlodipine and control groups {weighted mean difference [95% confidence interval = -0·16 (-0·51-0·19), P = 0·36]}. Similarly, there was insignificant difference in cardiac T2* between amlodipine and control groups {weighted mean difference [95% confidence interval = 0·34 (-0·01-0·69), P = 0·06]}. CONCLUSIONS: Despite the growing evidence supporting the role of amlodipine in reducing iron overload in thalassaemia patients, our meta-analysis did not find that evidence collectively significant. The results of our simulation suggest that when more data are available, a meta-analysis with more randomized clinical trials could provide more conclusive insights.

Torasemide versus furosemide in treatment of heart failure: A systematic review and meta-analysis of randomized controlled trials.

AIM: Diuretics are a cornerstone in treatment of heart failure (HF). Torasemide is a loop diuretic with a potential advantage over other diuretics. We aim to meta-analyse and compare the effect of torasemide with furosemide in HF patients. METHODS: A comprehensive literature search using 12 databases including PubMed, Scopus, and Web of Science was performed. All randomized controlled trials (RCTs) comparing furosemide and torasemide in HF patients were included and meta-analysed. We assessed the risk of bias using Cochrane Collaboration's tool. The protocol was registered in PROSPERO (CRD42016046112). RESULTS: Eighteen RCTs with 1598 patients were included. There was a significant difference between torasemide 20 mg and furosemide 40 mg in increasing the urine volume (standard difference of the mean (SDM) [95% confidence interval] = -0.78 [-1.52 to -0.053], P = .036). Torasemide 10 mg and 10 to 20 mg have a significant effect on potassium excretion in comparison with furosemide 25 to 40 mg (P = .018 and .023, respectively). In general, torasemide and furosemide have no significant difference in mortality, edema improvement, weight loss, heart rate, and reducing systolic/diastolic blood pressure. However, oral torasemide has a significant lower hospital stay P < .001 and superior effect in improving ejection fraction P = .029. CONCLUSION: Although not all results are statistically significant, torasemide has potential advantages on multiple aspects of HF management when compared with furosemide. More studies are needed to clarify these effects.

Mast cell mediators in relation to dengue severity: A systematic review and meta-analysis.

BACKGROUND: Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. We aimed to investigate the role of MCs in severity of dengue. METHODS: We searched for relevant studies in 10 databases on 15 August 2016. Meta-analysis (MA) was conducted by R version 3.5.0. RESULTS: We included 24 studies. in vivo and in vitro studies showed higher MC products released from infected mice/cells with dengue virus. In addition, when administering MC stabilizers or antihistaminic drugs, there was a decrease in vascular/capillary permeability. In human and at early stages, studies revealed an insignificant difference in VEGF levels in dengue fever (DF) versus dengue hemorrhagic fever (DHF) (standardized mean difference [SMD] 0.145; 95% confidence interval [CI], -0.348-0.638). Meanwhile, at acute stages and compared with healthy controls, high heterogeneity with an inconclusive difference in VEGF levels were noted in DF and DHF. However, pooled serum and plasma levels of VEGF were increased significantly in dengue shock syndrome (DSS) versus healthy controls (SMD 0.65; 95% CI, 0.3-0.95). There were also significantly higher chymase levels in DHF patients compared with DF during the acute phase (MD -6.531; 95% CI, -12.2 to -0.9). CONCLUSION: VEGF and chymase levels are mediators in dengue pathogenesis. However, limited data were available to support their role in severe dengue cases. Further studies are needed to evaluate the function of other mediators in dengue severity.

Therapeutic efficacy and safety of chamomile for state anxiety, generalized anxiety disorder, insomnia, and sleep quality: A systematic review and meta-analysis of randomized trials and quasi-randomized trials.

This systematic review and meta-analysis aimed to study the efficacy and safety of chamomile for the treatment of state anxiety, generalized anxiety disorders (GADs), sleep quality, and insomnia in human. Eleven databases including PubMed, Science Direct, Cochrane Central, and Scopus were searched to retrieve relevant randomized control trials (RCTs), and 12 RCTs were included. Random effect meta-analysis was performed by meta package of R statistical software version 3.4.3 and RevMan version 5.3. Our meta-analysis of three RCTs did not show any difference in case of anxiety (standardized mean difference = -0.15, 95% CI [-0.46, 0.16], P = 0.4214). Moreover, there is only one RCT that evaluated the effect of chamomile on insomnia and it found no significant change in insomnia severity index (P > 0.05). By using HAM-A scale, there was a significant improvement in GAD after 2 and 4 weeks of treatment (mean difference = -1.43, 95% CI [-2.47, -0.39], P = 0.007), (MD = -1.79, 95% CI [-3.14, -0.43], P = 0.0097), respectively. Noteworthy, our meta-analysis showed a significant improvement in sleep quality after chamomile administration (standardized mean difference = -0.73, 95% CI [-1.23, -0.23], P < 0.005). Mild adverse events were only reported by three RCTs. Chamomile appears to be efficacious and safe for sleep quality and GAD. Little evidence is there to show its effect on anxiety and insomnia. Larger RCTs are needed to ascertain these findings.

Beclabuvir in combination with asunaprevir and daclatasvir for hepatitis C virus genotype 1 infection: A systematic review and meta-analysis.

Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct-acting antivirals (DAAs) for patients with hepatitis C virus genotype 1 infection. This systematic review and meta-analysis investigating the efficacy and safety of this three-drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio (RR). The protocol was registered in PROSPERO (CRD42017054391). Among the included six studies, five studies were included for the meta-analysis (n = 1261). The three-drug combination showed a high response rate in naïve patients with sustained virologic response at week-12 posttreatment (SVR12 ) rate = 95.7% (95%CI [93.8-97.1]) and no difference detected by adding ribavirin (RBV) (the pooled RR = 0.98, 95%CI [0.90-1.08], P = 0.70) or comparing with interferon-experienced patients (RR = 1.02, 95%CI [0.98-1.07], P = 0.31) regardless the genotype 1 subtypes or IL28B genotype. Treatment failure was minimal and showed no difference regarding the previous comparisons. Increasing the dose or the duration did not show a significant increase in the efficacy. In conclusion, this analysis showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, ASV, and BCV irrespective of RBV use, prior interferon-based therapy, or restriction on non-cirrhotic patients, IL28B genotype, or baseline resistance-associated variants.