***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: BACKGROUND Combination treatments , preferably containing an artemisinin derivative , are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance . Our aim was to show non-inferiority of a new dispersible formulation of artemether-lumefantrine to the conventional crushed tablet in the treatment of young children with uncomplicated malaria . METHODS We did a r and omised non-inferiority study on children weighing 5 - 35 kg with uncomplicated P falciparum malaria in Benin , Kenya , Mali , Mozambique , and Tanzania . The primary outcome measure was PCR-corrected 28-day parasitological cure rate . We aim ed to show non-inferiority ( with a margin of -5 % ) of dispersible versus crushed tablet . We constructed an asymptotic one-sided 97.5 % CI on the difference in cure rates . A computer-generated r and omisation list was kept central ly and investigators were unaware of the study medication administered . We used a modified intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00386763 . FINDINGS 899 children aged 12 years or younger were r and omly assigned to either dispersible ( n=447 ) or crushed tablets ( n=452 ) . More than 85 % of patients in each treatment group completed the study . 812 children qualified for the modified intention-to-treat analysis ( n=403 vs n=409 ) . The PCR-corrected day-28 cure rate was 97.8 % ( 95 % CI 96.3 - 99.2 ) in the group on dispersible formulation and 98.5 % ( 97.4 - 99.7 ) in the group on crushed formulation . The lower bound of the one-sided 97.5 % CI was -2.7 % . The most common drug-related adverse event was vomiting ( n=33 [ 7 % ] and n=42 [ 9 % ] , respectively ) . No signs of ototoxicity or relevant cardiotoxicity were seen . INTERPRETATION A six-dose regimen of artemether-lumefantrine with the new dispersible formulation is as efficacious as the currently used crushed tablet in infants and children , and has a similar safety profile Background Artemether/lumefantrine ( AL ) has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region . Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria . However , oral paediatric formulations are urgently needed , as the tablets are difficult to administer to young children , who can not swallow whole tablets or tolerate the bitter taste of the crushed tablets . Methods A r and omized , controlled , open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6–59 months , treated over three days with either six-dose of artemether/lumefantrine tablets ( Coartem ® ) or three-dose of artemether/lumefantrine suspension ( Co-artesiane ® )  for uncomplicated falciparum malaria in western Kenya . The children were followed-up with clinical , parasitological and haematological evaluations over 28 days . Results Ninety three percent ( 124/133 ) and 90 % ( 121/134 ) children in the AL tablets and AL suspension arms respectively completed followed up . A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0 % at Day 28 in the AL tablets group and 93.4 % in the AL suspension group , p = 0.40 . Both drugs effectively cleared gametocytes and were well tolerated , with no difference in the overall incidence of adverse events . Conclusion The once daily three-dose of artemether-lumefantrine suspension ( Co-artesiane ® ) was not superior to six-dose artemether-lumefantrine tablets ( Coartem ® ) for the treatment of uncomplicated malaria in children below five years of age in western Kenya . Trial registration Clinical Trials.gov ZusammenfassungPädiatrische Medikamentenformulierungen sind ein wichtiger Fortschritt in der Therapie von afrikanischen Kindern , die an Malaria tropica erkrankt sind . In dieser klinischen Studie wurde die Wirksamkeit , Sicherheit und Verträglichkeit einer neuen pädiatrischen Artesunat-Mefloquin Koformulierung i m Vergleich mit einer Tablettenformulierung evaluiert . Einundsiebzig pädiatrische Patienten am Albert Schweitzer Spital in Lambaréné , Gabun , die an unkomplizierter Malaria tropica litten , wurden nach Körpergewicht stratifiziert , um mit der pädiatrischen ( 10 – 20 kg ; n = 41 ) oder der Tabletten-Formulierung ( 20 – 40 kg ; n = 30 ) therapiert zu werden . Die PCR korrigierte Heilungsrate war 100 % am Tag 28 . Die häufigsten Nebenwirkungen waren Erbrechen ( 17 % ) , abdominelle Schmerzen ( 11 % ) und Cephalea ( 17 % ) . Diese Studie bestätigt die hervorragende Wirksamkeit und gute Verträglichkeit von Artesunat-Mefloquin zur Therapie pädiatrischer Patienten in Afrika . Summary Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria . The aim of this clinical trial was to evaluate the efficacy , safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate-mefloquine and a new co-blister tablet formulation . A total of 71 children aged 1–13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight : 10–20 kg , pediatric group ( n = 41 ) ; 20–40 kg , tablet group ( n = 30 ) . All the children were treated once daily for three days : the pediatric group received the novel granule formulation , the tablet group received the co-blister tablets . The PCR-corrected cure rate on day 28 was evaluated . There was no reappearance of parasitemia during the follow-up period and the day-28 cure rate was therefore 100 % in per- protocol analysis . In intention-to-treat analysis the cure rates were 95 % in the pediatric group and 97 % in the tablet group . The most frequent adverse events were vomiting ( 17 % ) , abdominal pain ( 11 % ) and headache ( 17 % ) . This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children AIMS To assess the haemodynamic , electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin ( Artekin ) fixed combination therapy in uncomplicated malaria . METHODS Sixty-two Cambodians ( 32 children and 30 adults ) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure , the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring . QT intervals were rate-corrected ( QTc ) using Bazett 's formula . RESULTS Artekin therapy was well tolerated and all patients responded to treatment . Average parasite and fever clearance times were 19 and 12 h , respectively . The pretreatment mean fall in systolic blood pressure on st and ing was 8 + /- 6 mmHg and 6-hourly measurements over 72 h showed no significant change ( P = 0.48 ) . There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5 ) ( 95 % confidence interval 4 - 18 ms(0.5 ) ) relative to baseline at 24 h ( P = 0.003 ) . The maximal QTc prolongation observed in any patient was 53 ms(0.5 ) . There was a mean 0.4 mmol l(-1 ) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia ( plasma glucose < 3.0 mmol l(-1 ) ) were observed at any time . CONCLUSIONS Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults . Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine , no clinical ly significant cardiovascular or metabolic effects were observed OBJECTIVES Paediatric drug formulations of artemisinin combination therapies and pharmacokinetic data supporting their use in African children are urgently needed for the effective treatment of young children suffering from falciparum malaria in sub-Saharan Africa . PATIENTS AND METHODS In this study , the pharmacokinetic characteristics of a novel paediatric granule formulation of artesunate-mefloquine therapy were evaluated in comparison to the st and ard tablet formulation in the treatment of uncomplicated malaria in paediatric patients . Twenty-four patients were assigned to treatment according to body weight with either a fixed-dose paediatric granule co-formulation ( 10 - 20 kg body weight ) or a free-dose co-blister tablet formulation of artesunate-mefloquine ( > 20 - 40 kg body weight ) . RESULTS Median values for C(max ) ( 861 and 930 ng/mL ) , T(max ) ( 1.5 and 1.5 h ) and AUC(0-)(t ) ( 2,050 and 2,470 ng.h/mL ) were comparable for dihydroartemisinin in the two groups . Exploratory analysis of mefloquine plasma levels revealed a trend towards higher concentrations in the younger age group during the absorption phase ( 2,550 and 1,815 ng/mL , 54 h after initiation of treatment , respectively ) . Median mefloquine concentrations at day 28 were 197 and 343 ng/mL , respectively . CONCLUSIONS The pharmacokinetic characteristics of the two paediatric dosage forms , i.e. the novel fixed-dose co-formulation and the st and ard co-blister of artesunate-mefloquine show comparable results in the two treatment groups . The novel fixed-dose paediatric formulation is an interesting option for outpatient treatment of uncomplicated malaria in African children The bioavailability/pharmacokinetics of dihydroartemisinin and mefloquine following the oral doses of 4 mg/kg body weight artesunate ( Cambodian Pharmaceutical Enterprise ) given concurrently with 10 mg/kg body weight oral mefloquine artesunate ( Cambodian Pharmaceutical Enterprise ) were investigated in 15 healthy Cambodian male volunteers . Both formulations were generally well tolerated . Both produced satisfactory plasma/blood concentration-time profiles . Oral artesunate and mefloquine were rapidly absorbed from gastrointestinal tract with marked inter-individual variation . For the dihydroartemisinin , the median ( 95 % Cl ) Cmax of 748 ( 304 - 1,470 ) ng/ml was observed at 1.5 ( 0.3 - 3.0 ) hours ( tmax ) after drug administration . The median ( 95 % CI ) values for AUC0-infinity , lambda(z ) and tl/2z were 1.673 ( 1.08 - 2.88 ) microg.h/ml , 0.54(0.24 - 1.1)/hour and 1.3 ( 0.6 - 2.9 ) hours , respectively . For mefloquine , a median ( 95 % Cl ) Cmax of 1,000 ( 591 - 1,500 ) ng/ml was observed at 4 ( 2 - 6 ) hours ( tmax ) after drug administration . The median ( 95 % CI ) value for AUC0 - 168h was 3.92 ( 2.88 - 7.02 ) microg.h/ml The safety and efficacy of a novel combination of dihydroartemisinin ( DHA ) and piperaquine , Artekin ( Holleykin Pharmaceuticals ) , were assessed in 106 patients ( 76 children and 30 adults ) with uncomplicated falciparum malaria from 2 remote areas in Cambodia . Age-based doses were given at 0 , 8 , 24 , and 32 h. Mean total  DHA and piperaquine doses were 9.1 and 73.9 mg/kg , respectively , for children and 6.6 and 52.9 mg/kg for adults . All patients became aparasitemic within 72 h. Excluding the results for 1 child who died on day 4 , there was a 96.9 % 28-day cure rate ( 98.6 % in children and 92.3 % in adults ) . Patients who had recrudescent infection received low doses of Artekin . Side effects were reported by 22 patients ( 21 % ) but did not necessitate premature cessation of therapy . Although Artekin is a promising and 
    Output:
    
These data provide , for the first time , evidence for improved management of children by use of paediatric formulations , and support the further development and use of paediatric ACTs