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.Vox Sanguinis, 116(8), pp.887-897; 202

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue

Background: Considerable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators,among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase. Methods: This was a hospital-based prospective cohort study conducted in Vietnam.All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters(including progression to SD) until discharged. Plasma samples collected during acute phase (6-48 h before defervescence) were used to estimate the level of cfDNA. Results: Of the 61 dengue patients,SD patients (n = 8)developed shock syndrome in 4.8 days (95% CI 3.7-5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55-0.88; p = 0.0493).Conclusions: Taken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD

A systematic review finds underreporting of ethics approval, informed consent, and incentives in clinical trials

Objectives: In this study, we aim to review researchers’ reporting practices of the ethics statement, financial incentives, and local ethical committees’ profile in their clinical trials. Study Design and Setting: A systematic search was done through top-ranked 50 medical journals (Scimago Ranking) to retrieve 2,000 latest publications. Only primary clinical trials were included with no restriction to language or participants. Results: Among the 927 included trials, 14 trials (1.5%) did not report an ethical statement and two-third (63%) did not completely report the investigated components (Institutional Review eBoard approval, Helsinki Declaration, and informed consent). Moreover, 21 trials (2.26%) reported motivational incentives with the method and amount of payment for participants. Of them, 15 trials offered monetary incentives to participants in different forms. In the remaining six trials, the incentives were mainly medical benefits. Only one trial reported the profile or quality of local Institutional Review Board. Conclusion: A potential gap in the reporting practices of ethics statement and financial incentives was addressed in this review. Authors are urged to fully report all ethical components related to their study, including incentives and compensations plan. Medical journals are also recommended to implement further publication requirements concerning ethics reporting.Journal of Clinical Epidemiology, 91, pp.80-86; 201