The New England journal of medicine
-
Comparative Study
Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations.
Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. ⋯ Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.
-
Randomized Controlled Trial Clinical Trial
Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study.
Prophylactic blood transfusion has come to be regarded as necessary in the treatment of patients with sickle cell disease during pregnancy. Because of the risks associated with blood products and reports of successful outcomes without the use of blood transfusion, we conducted a prospective randomized controlled study of this issue. Seventy-two pregnant patients with sickle cell anemia were randomly assigned to one of two treatment groups: 36 received prophylactic transfusions of frozen red cells, and 36 received red-cell transfusions only for medical or obstetric emergencies. ⋯ Other medical and obstetric complications occurred with nearly equal frequency in the two randomized groups. Increases in costs, the number of hospitalizations, and the risk of alloimmunization were disadvantages of prophylactic transfusion. We conclude that the omission of prophylactic red-cell transfusion will not harm pregnant patients with sickle cell disease or their offspring.
-
Limited data are available on the relation between physical fitness and mortality from cardiovascular disease. We examined this question in a study of 4276 men, 30 to 69 years of age, whom we followed for an average of 8.5 years. Examinations at base line included assessment of conventional coronary risk factors and treadmill exercise testing. ⋯ The relative risk of death from cardiovascular causes was 2.7 (95 percent confidence interval, 1.4 to 5.1; P = 0.003) for healthy men with an increment of 35 beats per minute in the heart rate during stage 2, and 3.0 (95 percent confidence interval, 1.6 to 5.5; P = 0.0004) for those with a decrement of 4.4 minutes in the exercise time spent on the treadmill. The corresponding values for death from coronary heart disease were 3.2 (95 percent confidence interval, 1.5 to 6.7; P = 0.003) and 2.8 (95 percent confidence interval, 1.3 to 6.1; P = 0.007), respectively. We conclude that a lower level of physical fitness is associated with a higher risk of death from coronary heart disease and cardiovascular disease in clinically healthy men, independent of conventional coronary risk factors.