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Ridwanur Rahman, Vishal Goyal, Rashidul Haque, Kazi Jamil, Abul Faiz, Rasheda Samad, Sally Ellis, Manica Balasegaram, Margriet den Boer, Suman Rijal, Nathalie Strub-Wourgaft, Fabiana Alves, Jorge Alvar, Bhawna Sharma
Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh
www.plosntds.org
www.plosntds.org
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1.4003 0 Td
(patients)Tj
3.3675 0 Td
(were)Tj
2.1203 0 Td
(retested)Tj
3.3449 0 Td
(at)Tj
0.9524 0 Td
(day)Tj
1.6385 0 Td
(45.)Tj
-35.4385 -1.2983 Td
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3.4072 0 Td
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1.9388 0 Td
(presented)Tj
4.1159 0 Td
(positive)Tj
3.3165 0 Td
(parasitology)Tj
5.0797 0 Td
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0.9524 0 Td
(day)Tj
1.6384 0 Td
(45,)Tj
1.3947 0 Td
(or)Tj
1.0998 0 Td
(cases)Tj
2.2224 0 Td
(of)Tj
1.0148 0 Td
(relapse)Tj
2.999 0 Td
(following)Tj
3.9798 0 Td
(combina-)Tj
-33.1594 -1.2983 Td
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4.3597 0 Td
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1.0261 0 Td
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3.0047 0 Td
(rescue)Tj
2.7553 0 Td
(treatment)Tj
4.1329 0 Td
(with)Tj
1.9956 0 Td
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4.6828 0 Td
(15)Tj
1.1735 0 Td
(mg/kg.)Tj
3.0217 0 Td
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2.6476 0 Td
(who)Tj
1.9389 0 Td
(failed)Tj
-34.7015 -1.3039 Td
(to)Tj
1.0262 0 Td
(respond/relapsed)Tj
7.1091 0 Td
(following)Tj
3.9798 0 Td
(the)Tj
1.4684 0 Td
(reference)Tj
3.9174 0 Td
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4.3597 0 Td
(or)Tj
1.0998 0 Td
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2.6476 0 Td
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4.6828 0 Td
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1.7007 0 Td
(contra-indi-)Tj
-31.9915 -1.2982 Td
(cated,)Tj
2.5398 0 Td
(were)Tj
2.1146 0 Td
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1.0148 0 Td
(be)Tj
1.1395 0 Td
(rescued)Tj
3.2712 0 Td
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1.9842 0 Td
(sodium)Tj
3.2202 0 Td
(stibogluconate)Tj
6.0264 0 Td
(\(SSG\))Tj
2.5568 0 Td
(20mg/kg/day)Tj
5.4822 0 Td
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1.3776 0 Td
(30)Tj
1.1622 0 Td
(days,)Tj
2.211 0 Td
(or)Tj
1.0885 0 Td
(milte-)Tj
-35.189 -1.2983 Td
(fosine)Tj
2.6135 0 Td
(2.5mg/kg/day)Tj
5.7202 0 Td
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1.3833 0 Td
(28)Tj
1.1736 0 Td
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1.9956 0 Td
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6.0377 0 Td
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1.1792 0 Td
(the)Tj
1.474 0 Td
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4.4447 0 Td
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4.5297 0 Td
(of)Tj
-35.257 -1.3039 Td
(Bangladesh)Tj
4.7678 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(investigator's)Tj
5.4935 0 Td
(judgement.)Tj
4.7339 0 Td
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3.4129 0 Td
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1.9955 0 Td
(initial)Tj
2.5512 0 Td
(cure)Tj
1.9616 0 Td
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4.4447 0 Td
(with)Tj
2.0012 0 Td
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-34.5597 -1.2983 Td
(symptoms)Tj
4.3596 0 Td
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2.9253 0 Td
(follow-up)Tj
4.0932 0 Td
(were)Tj
2.126 0 Td
(suspected)Tj
4.0819 0 Td
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1.0148 0 Td
(relapse,)Tj
3.2201 0 Td
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1.7291 0 Td
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(for)Tj
1.3889 0 Td
(parasitological)Tj
-30.4835 -1.2983 Td
(confirmation)Tj
5.4991 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4684 0 Td
(CBMC)Tj
3.0217 0 Td
(hospital.)Tj
3.6 0 Td
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2.5965 0 Td
(outcomes)Tj
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(adverse)Tj
3.2202 0 Td
(events)Tj
2.7269 0 Td
(and)Tj
1.7291 0 Td
(serious)Tj
3.0387 0 Td
(adverse)Tj
-34.0608 -1.3039 Td
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3.7985 0 Td
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(treatment)Tj
4.1385 0 Td
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(6)Tj
0.6974 0 Td
(months)Tj
3.2825 0 Td
(afterwards.)Tj
4.6374 0 Td
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5.2214 0 Td
(were)Tj
2.1203 0 Td
(done)Tj
-33.5676 -1.2982 Td
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1.2755 0 Td
(the)Tj
1.4684 0 Td
(basis)Tj
2.1486 0 Td
(of)Tj
1.0148 0 Td
(clinical)Tj
3.0784 0 Td
(adverse)Tj
3.2145 0 Td
(events)Tj
2.7269 0 Td
(systematically)Tj
5.7429 0 Td
(at)Tj
0.9525 0 Td
(all)Tj
1.1508 0 Td
(study)Tj
2.3868 0 Td
(sites.)Tj
2.1543 0 Td
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1.2019 0 Td
(the)Tj
1.474 0 Td
(CBMC)Tj
3.016 0 Td
(hospital,)Tj
-33.0063 -1.2983 Td
(laboratory)Tj
4.3483 0 Td
(investigations)Tj
5.7202 0 Td
(included)Tj
3.7134 0 Td
(liver)Tj
1.9842 0 Td
(enzymes)Tj
3.6624 0 Td
(alanine)Tj
3.1237 0 Td
(aminotransferase)Tj
7.1093 0 Td
(\(ALAT\),)Tj
3.6453 0 Td
(aspartate)Tj
-33.3068 -1.3039 Td
(aminotransferase)Tj
7.1092 0 Td
(\(ASAT\),)Tj
3.583 0 Td
(bilirubin,)Tj
3.9514 0 Td
(prothrombin)Tj
5.4652 0 Td
(time,)Tj
2.2507 0 Td
(platelets,)Tj
3.6963 0 Td
(RBC)Tj
2.0807 0 Td
(count,)Tj
2.7552 0 Td
(WBC)Tj
2.4265 0 Td
(count,)Tj
-33.3182 -1.2983 Td
(random)Tj
3.4242 0 Td
(blood)Tj
2.5171 0 Td
(glucose)Tj
3.1748 0 Td
(\(RBS\),)Tj
2.8006 0 Td
(urea,)Tj
2.2054 0 Td
(creatinine,)Tj
4.4503 0 Td
(serum)Tj
2.7213 0 Td
(sodium,)Tj
3.4582 0 Td
(potassium,)Tj
4.5354 0 Td
(magnesium.)Tj
5.1137 0 Td
(At)Tj
1.2019 0 Td
(the)Tj
-35.6029 -1.2982 Td
(UZHC)Tj
2.9876 0 Td
(settings,)Tj
3.4696 0 Td
(laboratory)Tj
4.3483 0 Td
(parameters)Tj
4.6715 0 Td
(were)Tj
2.126 0 Td
(limited)Tj
3.067 0 Td
(to)Tj
1.0262 0 Td
(haemoglobin)Tj
5.4708 0 Td
(and)Tj
1.7348 0 Td
(random)Tj
3.4242 0 Td
(blood)Tj
2.5172 0 Td
(glu-)Tj
-34.8432 -1.2983 Td
(cose)Tj
1.9332 0 Td
(\(RBS\).)Tj
2.8006 0 Td
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1.4003 0 Td
(patients)Tj
3.3675 0 Td
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2.1203 0 Td
(assessed)Tj
3.4753 0 Td
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1.3833 0 Td
(dermal)Tj
3.0444 0 Td
(manifestations)Tj
6.0774 0 Td
(of)Tj
1.0148 0 Td
(leishmaniasis)Tj
5.5332 0 Td
(\(Para-KDL)Tj
4.6601 0 Td
(at)Tj
-36.8104 -1.3039 Td
(baseline,)Tj
3.6566 0 Td
(and)Tj
1.7291 0 Td
(PKDL)Tj
2.7269 0 Td
(at)Tj
0.9525 0 Td
(day)Tj
1.6384 0 Td
(15,)Tj
1.3946 0 Td
(45)Tj
1.1679 0 Td
(and)Tj
1.7348 0 Td
(at)Tj
0.9524 0 Td
(6)Tj
0.6917 0 Td
(months\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 438.1795 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Randomization)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 421.1716 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(A)Tj
0.9014 0 Td
(computer)Tj
4.1102 0 Td
(generated)Tj
4.1329 0 Td
(randomization)Tj
6.1681 0 Td
(code)Tj
2.0976 0 Td
(was)Tj
1.7008 0 Td
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2.058 0 Td
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(allocation.)Tj
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-34.0552 -1.2982 Td
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1.6497 0 Td
(opaque,)Tj
3.3619 0 Td
(sealed)Tj
2.6362 0 Td
(and)Tj
1.7348 0 Td
(sequentially)Tj
4.9549 0 Td
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4.371 0 Td
(envelopes)Tj
4.1215 0 Td
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2.126 0 Td
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3.8154 0 Td
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1.0262 0 Td
(each)Tj
2.0296 0 Td
(study)Tj
2.3867 0 Td
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-34.2139 -1.2983 Td
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2.0352 0 Td
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3.7644 0 Td
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3.5716 0 Td
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4.2689 0 Td
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1.4684 0 Td
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4.2859 0 Td
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3.0104 0 Td
(allocation)Tj
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1.0262 0 Td
(treatment.)Tj
4.3596 0 Td
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-33.4542 -1.2982 Td
(patients)Tj
3.3675 0 Td
(who)Tj
1.9389 0 Td
(fulfilled)Tj
3.2825 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4683 0 Td
(inclusion)Tj
3.9175 0 Td
(criteria,)Tj
3.2995 0 Td
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1.7631 0 Td
(none)Tj
2.245 0 Td
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1.0148 0 Td
(the)Tj
1.474 0 Td
(exclusion)Tj
3.9855 0 Td
(criteria)Tj
3.0784 0 Td
(and)Tj
1.7291 0 Td
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-33.7093 -1.304 Td
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2.7552 0 Td
(informed)Tj
3.9742 0 Td
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3.3335 0 Td
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1.0261 0 Td
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4.1329 0 Td
(regimens)Tj
3.9005 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
-36.2605 -1.2982 Td
(sealed)Tj
2.6362 0 Td
(envelopes.)Tj
4.3483 0 Td
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6.4119 0 Td
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1.7008 0 Td
(stratified)Tj
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(centre)Tj
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2.3924 0 Td
(an)Tj
-34.9282 -1.2983 Td
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(allocation)Tj
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(ratio)Tj
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1.3833 0 Td
(married)Tj
3.4355 0 Td
(women,)Tj
3.4299 0 Td
(men,)Tj
2.2337 0 Td
(and)Tj
1.7291 0 Td
(children)Tj
3.5603 0 Td
(firstly;)Tj
2.7326 0 Td
(and)Tj
1.7291 0 Td
(further)Tj
3.0274 0 Td
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1.9956 0 Td
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(equal)Tj
-35.0473 -1.3039 Td
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2.0976 0 Td
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1.0318 0 Td
(single)Tj
2.5341 0 Td
(women)Tj
3.2032 0 Td
(of)Tj
1.0148 0 Td
(childbearing)Tj
5.227 0 Td
(potential.)Tj
3.9855 0 Td
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2.6475 0 Td
(women)Tj
3.2032 0 Td
(of)Tj
1.0148 0 Td
(childbearing)Tj
5.227 0 Td
(age)Tj
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(were)Tj
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-34.8545 -1.2983 Td
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3.702 0 Td
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1.0261 0 Td
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3.0104 0 Td
(either)Tj
2.5285 0 Td
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4.6828 0 Td
(alone)Tj
2.3811 0 Td
(or)Tj
1.0941 0 Td
(AmBisome)Tj
4.6828 0 Td
(+)Tj
0.7994 0 Td
(paromomycin.)Tj
6.1171 0 Td
(The)Tj
1.7802 0 Td
(allocation)Tj
-31.8045 -1.2982 Td
(ratio)Tj
2.0976 0 Td
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1.6951 0 Td
(adjusted)Tj
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1.0261 0 Td
(account)Tj
3.3846 0 Td
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1.3833 0 Td
(this,)Tj
1.8992 0 Td
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1.0374 0 Td
(order)Tj
2.4208 0 Td
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1.0261 0 Td
(achieve)Tj
3.1748 0 Td
(approximately)Tj
5.9754 0 Td
(equal)Tj
2.3584 0 Td
(numbers)Tj
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1.0375 0 Td
(each)Tj
2.0239 0 Td
(arm.)Tj
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(the)Tj
1.4683 0 Td
(allocation)Tj
4.1329 0 Td
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(1:1:1:1)Tj
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(treatments)Tj
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(married)Tj
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3.4242 0 Td
(men,)Tj
2.2393 0 Td
(and)Tj
1.7292 0 Td
(children;)Tj
3.7814 0 Td
(and)Tj
1.7291 0 Td
(1:1)Tj
1.4003 0 Td
(\(for)Tj
1.7234 0 Td
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4.6828 0 Td
(alone)Tj
2.3811 0 Td
(or)Tj
1.0999 0 Td
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4.6771 0 Td
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0.7994 0 Td
(paromomycin\))Tj
6.2305 0 Td
(in)Tj
-35.8977 -1.2983 Td
(single)Tj
2.5284 0 Td
(women)Tj
3.2032 0 Td
(of)Tj
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(childbearing)Tj
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1.9842 0 Td
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(open-label)Tj
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(miltefosine)Tj
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(an)Tj
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(medication)Tj
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(paromomycin)Tj
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1.4457 0 Td
(administered)Tj
5.4878 0 Td
(IV)Tj
1.2586 0 Td
(and)Tj
1.7291 0 Td
(IM)Tj
-34.1799 -1.304 Td
(respectively.)Tj
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Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 203.9811 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
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3.5716 0 Td
(size)Tj
1.9749 0 Td
(and)Tj
1.8661 0 Td
(study)Tj
2.5843 0 Td
(populations)Tj
ET
Q
q
1 j
1 J
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10 0 0 10 200.0125 186.9732 cm
BT
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1 TL
-0.004 Tc
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1.7801 0 Td
(sample)Tj
3.0217 0 Td
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1.6838 0 Td
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1.7008 0 Td
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(assuming)Tj
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(a)Tj
0.652 0 Td
(treatment)Tj
4.1386 0 Td
(success)Tj
3.101 0 Td
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(97%)Tj
1.9276 0 Td
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(the)Tj
1.4683 0 Td
(reference)Tj
3.9175 0 Td
(arm)Tj
-33.6527 -1.2982 Td
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5.3631 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.652 0 Td
(margin)Tj
3.1237 0 Td
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1.0148 0 Td
(non-inferiority)Tj
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1.6554 0 Td
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(7%,)Tj
1.6781 0 Td
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1.0262 0 Td
(a)Tj
0.6576 0 Td
(mini-)Tj
-34.9906 -1.2983 Td
(mally)Tj
2.4207 0 Td
(acceptable)Tj
4.3483 0 Td
(cure)Tj
1.9673 0 Td
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1.7461 0 Td
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(each)Tj
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(a)Tj
0.652 0 Td
(power)Tj
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1.0148 0 Td
(90%,)Tj
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(sample)Tj
3.0217 0 Td
(size)Tj
1.6838 0 Td
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-36.2038 -1.2982 Td
(group)Tj
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(the)Tj
1.4683 0 Td
(sample)Tj
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1.0148 0 Td
(married)Tj
3.4356 0 Td
(women,)Tj
3.4242 0 Td
(men)Tj
2.0126 0 Td
(and)Tj
1.7291 0 Td
(children)Tj
3.5603 0 Td
(would)Tj
2.7099 0 Td
(be)Tj
1.1509 0 Td
(140.)Tj
1.8708 0 Td
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2.5455 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(possible)Tj
-34.3386 -1.304 Td
(teratogenic)Tj
4.6771 0 Td
(effect)Tj
2.3641 0 Td
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1.0148 0 Td
(miltefosine)Tj
4.6714 0 Td
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1.7292 0 Td
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