***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Introduction Sideroblastic cardiomyopathy secondary to repeated blood transfusions is a feared complication in thalassaemia .  Control of myocardial iron is thus becoming the cornerstone of thalassaemia management . Recent evidence suggests a role for L-type Ca2 + channels in mediating iron uptake by the heart . Blocking the cellular iron uptake through these channels may add to the benefit of therapy to st and ard chelation in reducing myocardial iron . We aim to determine the efficacy of amlodipine ( a calcium channel blocker ) as an adjunct to st and ard aggressive chelation in retarding myocardial iron deposition in thalassaemics with or without cardiomyopathy . Outcomes The primary outcome is to compare the efficacy of amlodipine+chelation ( intervention ) versus st and ard chelation ( control ) in retarding myocardial iron deposition . Secondary outcomes include the effect of amlodipine therapy on systolic and diastolic function , strain and strain rate and liver iron content . Methods and analysis This is a single-centre , parallel-group , prospect i ve r and omised control trial . Twenty patients will be r and omised in a 1:1 allocation ratio into the intervention and control arms . In addition to conventional echocardiography , MRI T2 * values for assessment of cardiac and liver iron load will be obtained at baseline and at 6 and 12 months . Cardiac T2 * will be reported as the geometric mean and per cent coefficient of variation , and an increase in cardiac T2 * values from baseline will be used as an end point to compare the efficacy of therapy . A p Value of < 0.05 will be considered significant . Study setting Department of Pediatric and Child Health , Aga Khan University Hospital , Karachi , Pakistan . Ethics and dissemination This study has been approved by the Ethics Review Committee and Clinical Trials Unit at The Aga Khan University with respect to scientific content and compliance with applicable research and human subjects regulations . Findings will be reported through scientific publications and research conferences and project summary papers for participants . Trial registration number Clinical Trials . Gov . Registration no : NCT02065492 Background — The goal of this study was to determine the predictive value of cardiac T2 * magnetic resonance for heart failure and arrhythmia in thalassemia major . Methods and Results — We analyzed cardiac and liver T2 * magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans . The relative risk for heart failure with cardiac T2 * values < 10 ms ( compared with > 10 ms ) was 160 ( 95 % confidence interval , 39 to 653 ) . Heart failure occurred in 47 % of patients within 1 year of a cardiac T2 * < 6 ms with a relative risk of 270 ( 95 % confidence interval , 64 to 1129 ) . The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2 * ( 0.948 ) than for liver T2 * ( 0.589 ; P<0.001 ) or serum ferritin ( 0.629 ; P<0.001 ) . Cardiac T2 * was < 10 ms in 98 % of scans in patients who developed heart failure . The relative risk for arrhythmia with cardiac T2 * values < 20 ms ( compared with > 20 ms ) was 4.6 ( 95 % confidence interval , 2.66 to 7.95 ) . Arrhythmia occurred in 14 % of patients within 1 year of a cardiac T2 * of < 6 ms . The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2 * ( 0.747 ) than for liver T2 * ( 0.514 ; P<0.001 ) or serum ferritin ( 0.518 ; P<0.001 ) . The cardiac T2 * was < 20 ms in 83 % of scans in patients who developed arrhythmia . Conclusions — Cardiac T2 * magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron . Using cardiac T2 * for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00520559 Deferasirox ( ICL670 ) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions . A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older . Patients were r and omized and received treatment with deferasirox ( n = 296 ) or deferoxamine ( n = 290 ) , with dosing of each according to baseline liver iron concentration ( LIC ) . The primary endpoint was maintenance or reduction of LIC ; secondary endpoints included safety and tolerability , change in serum ferritin level , and net body iron balance . In both arms , patients with LIC values of 7 mg Fe/g dry weight ( dw ) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin , and effects on net body iron balance . However , the primary endpoint was not met in the overall population , possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw . The most common adverse events included rash , gastrointestinal disturbances , and mild nonprogressive increases in serum creatinine . No agranulocytosis , arthropathy , or growth failure was associated with deferasirox administration . Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload BACKGROUND Iron chelation therapy ( ICT ) with deferoxamine ( DFO ) , the current st and ard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia , requires regular subcutaneous or intravenous infusions . This can lead to reduced quality of life and poor adherence , result ing in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia .  Deferasirox is an orally administered iron chelator that has been approved for use in the United States , Switzerl and , and other countries . OBJECTIVE This analysis was conducted to compare patient-reported outcomes ( PROs ) during receipt of DFO infusions or once-daily oral therapy with deferasirox ( ICL670 ) . METHODS PROs were prospect ively evaluated as part of a r and omized , Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients ( age > or = 2 years ) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or = 2 mg/g dry weight . PRO question naires were completed by patients or a parent or legal guardian at baseline , week 4 , week 24 , and end of study ( EOS ) . Patients assessed their level of satisfaction with study treatment ( very satisfied , satisfied , neutral , dissatisfied , or very dissatisfied ) and rated its convenience ( very convenient , convenient , neutral , inconvenient , or very inconvenient ) . Time lost from normal activities due to  ICT  in the previous 4 weeks was recorded using a single global assessment . At week 4 , patients who had previous experience with DFO were asked to indicate their preference for treatment  ( ICT received before the study , ICT received during the study , no preference , or no response ) and the reason for that preference . At EOS , all patients were asked if they would be willing to continue using the ICT they had received during the study . All study analyses were performed in all patients who received at least 1 dose of study medication . RESULTS Five hundred eighty-six patients ( 304 females , 282 males ; age range , 2 - 53 years ) received treatment with DFO ( n = 290 ) or deferasirox ( n = 296 ) . Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO ( week 4 : 92.0 % vs 50.4 % , respectively ; week 24 : 89.6 % vs 44.0 % ; EOS : 85.1 % vs 38.7 % ; all , P < 0.001 ) . At the same time points , the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO ( 95.5 % vs 21.3 % , 91.7 % vs 17.4 % , and 92.7 % vs 11.3 % , respectively ; all , P < 0.001 ) . Among patients who had previously taken DFO and were r and omized to receive deferasirox  during the study , 96.9 % reported a preference for deferasirox over DFO . At EOS , the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO ( 85.8 % vs 13.8 % ; P < 0.001 ) . CONCLUSIONS In this study , patient-reported satisfaction and convenience were significantly higher for the once-daily , oral ICT deferasirox than for DFO infusions . Among patients who had received DFO before the study , the majority indicated a preference for deferasirox over DFO . Most patients receiving deferasirox indicated that they would be willing to continue taking it . These results suggest that deferasirox had a positive impact on patients ' daily lives There are conflicting results concerning the anti-ischemic effect of nifedipine in patients with chronic stable angina . Therefore , the purpose of this study was to assess whether the anti-ischemic effect of nifedipine may be related to coronary collateral circulation . Forty-one patients with stable angina and coronary artery disease were r and omized to a parallel double-blind study with nifedipine and metoprolol , and compared for effects on transient ischemic episodes during ambulatory electrocardiographic monitoring and exercise-induced ischemia . The effects were correlated to the presence of collateral circulation . In 17 patients , angiographically poor or no collateral flow was observed ( group 1 ) , and 24 had good collateral flow ( group 2 ) . Nifedipine was administered to 20 patients ( 8 in group 1 , and 12 in group 2 ) . In group 1 , nifedipine reduced the frequency of total and asymptomatic ischemic episodes ( p < 0.05 ) , whereas significant increases in both total ( p < 0.05 ) and silent ( p < 0.01 ) ischemia were observed in group 2 . Exercise variables were slightly improved ( p = NS ) during nifedipine therapy in group 1 , and slightly worsened ( p = NS ) in group 2 . Reflex tachycardia was not observed at either the onset of transient ischemia out of the hospital or exercise-induced ischemia . This was in contrast with the effect in 21 patients treated with metoprolol ( 9 in group 1 , and 12 in group 2 ) where significant reductions were observed in the frequency of both total ( p < 0.01 ) and silent ( p < 0.01 ) ischemia in both groups . Furthermore , a beneficial effect was observed on all exercise variables . ( ABSTRACT TRUNCATED AT 250 WORDS The identification of a safe , orally active iron chelator is critically important for the prevention of morbidity and early death in patients receiving regular red cell transfusions . Based on our findings in a 1-year multicenter , prospect i ve study of the safety and efficacy of deferiprone in patients with thalassemia major , we have extended the treatment period to 4 years . The mean dose of the chelator was 73 mg/kg per day during 531 patient-years . The rates of agranulocytosis ( absolute neutrophil count [ ANC ] < 500 x 10(9)/L ) and milder forms of neutropenia ( ANC , 500 - 1500 x 10(9)/L ) were 0.2 and 2.8 per 100 patient-years , respectively . Neutropenia occurred significantly more commonly in patients with intact spleens . Gastrointestinal and joint symptoms decreased significantly after the first year of therapy , and led to discontinuation of deferiprone in only one patient in years 2 to 4 . The mean alanine aminotransferase ( ALT ) value of 71 U/L after 4 years of therapy was significantly higher than the baseline value of 61 U/L. Trend analysis showed no increase in the ALT levels or the percentage of patients with ALT levels greater than twice the upper limit of the reference range . Ferritin levels did not change significantly from the values at the time of change from deferoxamine to deferiprone in either the intention-to-treat analysis or in the 84 patients who completed 4 years of therapy . Because of concerns regarding the effectiveness of the studied dose of deferiprone , 47 patients discontinued therapy , whereas 15 patients interrupted therapy because of concerns regarding low iron levels . The results of this study help to define the safety and effectiveness of long-term therapy with deferiprone Nifedipine augments baroreflex mechanisms in in vivo animal models . Previous studies in our laboratory demonstrate that nifedipine potentiates baroreflex control of heart rate and vascular resistance in normal 
    Output:
    
The available evidence does not clearly suggest that the use of calcium channel blockers is associated with a reduction in myocardial iron in people with transfusion-dependent beta thalassaemia , although a potential for this was seen .