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Objectives:To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. Design:Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose.Setting:Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans.Participants:126 healthy adults 21–45 years of age.Interventions:10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13.Outcome Measures:Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation.Results:No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ.Conclusions:These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics.

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Assumptions that psychological attributes are specific to particular diagnoses characterize many investigations of chronically ill patients. We studied 758 patients, each of whom had one of six different chronic illnesses, to determine and compare their scores on the Mental Health Index. Five groups of physically ill patients (with arthritis, diabetes, cancer, renal disease, or dermatologic disorders) did not differ significantly from one another or from the general public, but all had significantly higher scores for psychological status when compared with the sixth group, patients under treatment for depression. There was a significant direct relation between higher mental-health scores and advancing age across all patient populations. Patients with recently diagnosed illness in all groups had poorer mental-health scores than did patients whose illness had been diagnosed more than four months previously. A direct relation between declining physical status and mental-health scores was observed. These results suggest that psychological adaptation among patients with chronic illnesses is remarkably effective and fundamentally independent of specific diagnosis.