Publications

OBJECTIVES

To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.

DESIGN

Randomized single-blinded clinical trial.

SETTING

Apac, Uganda, an area of very high malaria transmission intensity.

PARTICIPANTS

Children aged 6 mo to 10 y with uncomplicated falciparum malaria.

INTERVENTION

Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.

OUTCOME MEASURES

Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.

RESULTS

Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%-26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%-19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%-12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%-16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.

CONCLUSION

DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.

OBJECTIVE

To examine the relationship between cardiac self-efficacy and health status, including symptom burden, physical limitation, quality of life, and overall health among outpatients with stable coronary heart disease (CHD). We hypothesized that lower self-efficacy would predict worse health status, independent of CHD severity and depression.

METHODS

We performed a cross-sectional study of 1024 outpatients with CHD, who were recruited between 2000 and 2002 for the Heart and Soul Study. We administered a validated measure of cardiac self-efficacy, assessed cardiac function using exercise treadmill testing with stress echocardiography, and measured depressive symptoms using the Patient Health Questionnaire. Health status outcomes (symptom burden, physical limitation, and quality of life) were assessed using the Seattle Angina Questionnaire, and overall health was measured as fair or poor (versus good, very good, or excellent).

RESULTS

After adjustment for CHD severity and depressive symptoms, each standard deviation (4.5-point) decrease in self-efficacy score was independently associated with greater symptom burden (adjusted odds ratio (OR) = 2.1, p = .001), greater physical limitation (OR = 1.8, p < .0001), worse quality of life (OR = 1.6, p < .0001), and worse overall health (OR = 1.9, p < .0001). Depressive symptoms and poor treadmill exercise capacity were also associated with poor health status, but left ventricular ejection fraction and ischemia were not.

CONCLUSIONS

Among patients with CHD, low cardiac self-efficacy is associated with poor health status, independent of CHD severity and depressive symptoms. Further study should examine if self-efficacy constitutes a useful target for cardiovascular disease management interventions.

OBJECTIVES

ABCB1 encodes the efflux transporter P-glycoprotein (P-gp), which regulates the intracellular concentration of many xenobiotics, including several HIV protease inhibitors (PIs). Exposure to some xenobiotics, such as the antibiotic rifampicin, increases P-gp expression. In the present study, we investigated the effect of the HIV PIs saquinavir and atazanavir on the expression and function of ABCB1 and P-gp in primary and cultured lymphocytes, as well as the molecular interactions between these drugs and P-gp. ABCB1 and P-gp expression and function were examined in lymphocyte samples from healthy subjects before and after atazanavir-boosted saquinavir treatment. Expression and function were also studied in CEM cells following exposure to atazanavir and saquinavir. The inhibitory effects of these drugs were investigated in ABCB1-transfected HEK293T cells.

METHODS

P-gp expression and function were measured by flow cytometry. ABCB1 mRNA expression was evaluated using quantitative RT-PCR.

RESULTS

There were no overall changes in ABCB1 or P-gp expression or function after saquinavir-atazanavir treatment in primary lymphocyte samples. However, there was considerable interindividual variability in baseline lymphocyte ABCB1 expression, as well as in the degree of change in ABCB1 expression after saquinavir-atazanavir administration. In cell culture, 5 microM saquinavir increased ABCB1 levels, although it did not affect P-gp expression. Atazanavir inhibited P-gp function at concentrations above therapeutic levels.

CONCLUSIONS

Differences in lymphocyte ABCB1 expression, which may be caused by genetic polymorphisms in ABCB1 or its regulatory partners, are a likely cause of interindividual variation in the disposition and efficacy of clinically relevant P-gp substrates, including HIV PIs.

Little is known about practice patterns regarding the diagnosis and management of idiopathic pulmonary fibrosis (IPF). This study attempts to define the practice patterns of academic pulmonologists caring for patients with IPF. Academic pulmonologists in the United States were surveyed electronically. Completed surveys were received from 272 respondents (representing approximately 10% of academic pulmonologists). The majority agreed that high-resolution computed tomography can establish the diagnosis of IPF, and that surgical lung biopsy is indicated when the diagnosis remains unclear. Bronchoscopy is little utilized. Most respondents treat patients with medications, but there is no consensus regarding treatment regimen. These results suggest there is general consensus regarding the approach to diagnosis, but that there is no consensus about medical management in IPF.