1.
Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials.
Maggio, A, Filosa, A, Vitrano, A, Aloj, G, Kattamis, A, Ceci, A, Fucharoen, S, Cianciulli, P, Grady, RW, Prossomariti, L, et al
Blood cells, molecules & diseases. 2011;(3):166-75
Abstract
The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality (GRADE). The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference during DFX 30 mg/kg versus DFO (p=0.70), no statistically significant variations in heart T2* signal during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary iron excretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 and p<0.00001, respectively). These findings do not support any specific chelation treatment. The literature shows risks of bias, and additional larger and longer trials are needed.
2.
Effect of sodium iron ethylenediaminetetra-acetate (NaFeEDTA) on haemoglobin and serum ferritin in iron-deficient populations: a systematic review and meta-analysis of randomised and quasi-randomised controlled trials.
Wang, B, Zhan, S, Xia, Y, Lee, L
The British journal of nutrition. 2008;(6):1169-78
Abstract
We aimed to synthesise evidence to assess the effect and safety of NaFeEDTA on Hb and serum ferritin in Fe-deficient populations. We performed a systematic review, identifying potential studies by searching the electronic databases of Medline, Cochrane Library, Embase, WHO Library and China National Knowledge Infrastructure. We also hand-searched relevant conference proceedings and reference lists. Finally, we contacted experts in the field. The selection criteria included randomised or quasi-randomised controlled trials of NaFeEDTA compared with placebo. Hb, serum ferritin and adverse effects were outcomes of interest. Inclusion decisions, quality assessment and data extraction were performed by two reviewers independently. Seven studies met the inclusion criteria. All included studies assessed the effect of NaFeEDTA on Hb concentration, four studies assessed the effect on serum ferritin concentration, and one study on serum Zn concentration. After the intervention, Hb concentration and serum ferritin concentration were both higher in the NaFeEDTA group compared with the control group. For Hb, data from six studies could be pooled and the pooled estimate (weighted mean difference) was 8.56 (95 % CI 2.21, 14.90) g/l (P = 0.008). For serum ferritin, data from four studies could be pooled and the pooled difference was 1.58 (95 % CI 1.20, 2.09) microg/l (P < 0.001). Subgroup analysis indicated that a lower baseline Hb level was associated with a greater increase in Hb concentration. No significant difference in serum Zn concentration was found. We concluded that NaFeEDTA increased both Hb concentration and serum ferritin concentration substantially in Fe-deficient populations, and could be an effective Fe preparation to combat Fe deficiency.
3.
Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia.
Roberts, DJ, Rees, D, Howard, J, Hyde, C, Alderson, P, Brunskill, S
The Cochrane database of systematic reviews. 2005;(4):CD004450
Abstract
BACKGROUND Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy. OBJECTIVES To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia. SEARCH STRATEGY We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004. SELECTION CRITERIA Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators. MAIN RESULTS Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials. AUTHORS' CONCLUSIONS We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.
4.
Chromium picolinate for reducing body weight: meta-analysis of randomized trials.
Pittler, MH, Stevinson, C, Ernst, E
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2003;(4):522-9
Abstract
The aim of this meta-analysis was to assess the evidence of chromium picolinate for reducing body weight. Literature searches were conducted on Medline, Embase, The Cochrane Library, Amed and Ciscom. Nine experts and four manufacturers of commercial preparations containing chromium picolinate were asked to contribute published and unpublished studies. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, validation and the assessment of methodological quality were performed independently by two reviewers. To be included, studies were required to state that they were randomized, double-blind and placebo-controlled, and report on body weight. Ten trials met all inclusion criteria and provided data, which were suitable for statistical pooling. For body weight a significant differential effect was found in favour of chromium picolinate (weighted mean difference: -1.1 kg; 95% confidence interval (CI): -1.8 to -0.4 kg, n=489). Sensitivity analysis suggests that this effect is largely dependent on the results of a single trial (weighted mean difference: -0.9 kg; 95% CI: -2.0 to 0.2 kg, n=335). Three of the reviewed trials reported on adverse events, indicating their absence in the treatment groups. In conclusion, our meta-analysis suggests a relatively small effect of chromium picolinate compared with placebo for reducing body weight. The clinical relevance of the effect is debatable and the lack of robustness means that the result has to be interpreted with caution.