***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature

***DOCUMENTATION***

***EXAMPLES***

Input: A total of 17 trials involving 1061 participants (range 13 to 213 participants per trial) were included. Of these, 16 trials compared either deferiprone alone with desferrioxamine alone, or a combined therapy of deferiprone and desferrioxamine with either deferiprone alone or desferrioxamine alone; one compared different schedules of deferiprone. There was little consistency between outcomes and limited information to fully assess the risk of bias of most of the included trials. Four trials reported mortality; each reported the death of one individual receiving deferiprone with or without desferrioxamine. One trial reported five further deaths in patients who withdrew from randomised treatment (deferiprone with or without desferrioxamine) and switched to desferrioxamine alone. Seven trials reported cardiac function or liver fibrosis as measures of end organ damage. Earlier trials measuring the cardiac iron load indirectly by magnetic resonance imaging (MRI) T2* signal had suggested deferiprone may reduce cardiac iron more quickly than desferrioxamine. However, a meta-analysis of two trials suggested that left ventricular ejection fraction was significantly reduced in patients who received desferrioxamine alone compared with combination therapy. One trial, which planned five years of follow up, was stopped early due to the beneficial effects of combined treatment compared with deferiprone alone in terms of serum ferritin levels reduction. The results of this and three other trials suggest an advantage of combined therapy over monotherapy to reduce iron stores as measured by serum ferritin. There is, however, no conclusive or consistent evidence for the improved efficacy of combined deferiprone and desferrioxamine therapy over monotherapy from direct or indirect measures of liver iron. Both deferiprone and desferrioxamine produce a significant reduction in iron stores in transfusion-dependent, iron-overloaded people. There is no evidence from randomised controlled trials to suggest that either has a greater reduction of clinically significant end organ damage. Evidence of adverse events were observed in all treatment groups. Occurrence of any adverse event was significantly more likely with deferiprone than desferrioxamine in one trial, RR 2.24 (95% CI 1.19 to 4.23). Meta-analysis of a further two trials showed a significant increased risk of adverse events associated with combined deferiprone and desferrioxamine compared with desferrioxamine alone, RR 3.04 (95% CI 1.18 to 7.83). The most commonly reported adverse event was joint pain, which occurred significantly more frequently in patients receiving deferiprone than desferrioxamine, RR 2.64 (95% CI 1.21 to 5.77). Other common adverse events included gastrointestinal disturbances as well as neutropenia or leucopenia, or both. In the absence of data from randomised controlled trials, there is no evidence to suggest the need for a change in current treatment recommendations; namely that deferiprone is indicated for treating iron overload in people with thalassaemia major when desferrioxamine is contraindicated or inadequate. Intensified desferrioxamine treatment (by either subcutaneous or intravenous route) or use of other oral iron chelators, or both, remains the established treatment to reverse cardiac dysfunction due to iron overload. Indeed, the US Food and Drug Administration (FDA) recently only gave support for deferiprone to be used as a last resort for treating iron overload in thalassaemia, myelodysplasia and sickle cell disease. However, there is evidence that adverse events are increased in patients treated with deferiprone compared with desferrioxamine and in patients treated with combined deferiprone and desferrioxamine compared with desferrioxamine alone. There is an urgent need for adequately-powered, high-quality trials comparing the overall clinical efficacy and long-term outcome of deferiprone with desferrioxamine.
Output:

Seventeen randomised controlled trials compared deferiprone with desferrioxamine. They report little data on death or end organ damage, so we report the effects of therapy using mainly other markers. Removing excess iron was assessed by iron concentration in the blood and liver; heart function; and the amount of iron passed in urine. However, the amount of iron removed with either deferiprone or desferrioxamine was not consistent; one reason being that outcomes were measured differently. This makes it difficult to compare results between trials. Adverse events included joint pain, nausea, stomach upsets and low white blood cell count with deferiprone and pain or skin reactions at the injection site and joint pain with desferrioxamine. In one trial, the risk of an adverse event with deferiprone was twice that of the risk with desferrioxamine. Two further trials showed a three-fold increased risk of an adverse event with combined deferiprone and desferrioxamine therapy compared with desferrioxamine alone. We found no evidence to change current recommendations to treat iron overload in thalassaemia with deferiprone when desferrioxamine cannot be used or is inadequate. Intensified desferrioxamine treatment or use of other oral iron chelators (or both of these) remains the established treatment to reverse heart problems due to iron overload. Indeed, the US Food and Drug Administration (FDA) recently gave support for deferiprone only to be used as a last resort treatment in patients with thalassaemia, myelodysplasia and sickle cell disease. The danger of raised liver enzymes or a very low white blood cell count with deferiprone means that this treatment should not be used unless close monitoring of full blood counts and liver function is possible. Large trials of chelation therapy with standardised measures of iron stores and end organ damage are needed so valuable trial data can be compared and analysed.