Publications

BACKGROUND

Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children.

METHODS

A total of 351 children aged 6 weeks to 12 months were enrolled and followed up for up to 1 year. Children who were at least 4 months of age, weighted at least 5 kg, and had been diagnosed as having their first episode of uncomplicated malaria were randomized to receive artemether-lumefantrine or dihydroartemisinin-piperaquine. The same treatment was given for all subsequent episodes of uncomplicated malaria. Recrudescent and new infections were distinguished by polymerase chain reaction genotyping. Outcomes included the risk of recurrent malaria after individual treatments and the incidence of malaria treatments for individual children after randomization.

RESULTS

A total of 113 children were randomized to artemether-lumefantrine and 119 to dihydroartemisinin-piperaquine, resulting in 320 and 351 treatments for uncomplicated falciparum malaria, respectively. Artemether-lumefantrine was associated with a higher risk of recurrent malaria after 28 days (35% vs 11%; P = .001]). When the duration of follow-up was extended, differences in the risk of recurrent malaria decreased such that the overall incidence of malaria treatments was similar for children randomized to artemether-lumefantrine, compared with those randomized to dihydroartemisinin-piperaquine (4.82 vs 4.61 treatments per person-year; P = .63). The risk of recurrent malaria due to recrudescent parasites was similarly low in both treatment arms.

CONCLUSIONS

Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria. Clinical trials registration. NCT00527800.

BACKGROUND

Hypertriglyceridemia is associated with insulin resistance, type 2 diabetes, and the metabolic syndrome. Membrane glycoprotein PC-1 (also termed ENPP1) is a direct insulin receptor inhibitor, and certain polymorphisms of the ENPP1/PC-1 gene have been associated with insulin resistance, type 2 diabetes, obesity, and diabetic complications.

METHODS

We examined the effect of 3 ENPP1/PC-1 variants (K121Q, rs1044498, and IVS20delT-11, rs1799774, and A-->G+1044TGA, rs7754561) on plasma triglyceride levels in 1112 subjects of non-Hispanic American white European ancestry.

RESULTS

Two of the ENPP1/PC-1 variants--A-->G+1044TGA (odds ratio [OR] 1.48, 95% confidence interval [CI], 1.54-1.82, P = 0.002) and IVS20delT-11 (OR 1.41, 95% CI, 1.08-1.84, P = 0.012)--were significantly associated with hypertriglyceridemia. Haplotype analyses also revealed an association with hypertriglyceridemia. In the variant analyses and in the haplotype analysis, the associations with hypertriglyceridemia were observed in male but not female subjects. Interestingly, the more widely studied K121Q ENPP1/PC-1 variant was not associated with hypertriglyceridemia in any group or subgroup analysis.

CONCLUSION

In the present study, we find that genetic variants of the ENPP1/PC-1 gene are associated with hypertriglyceridemia in male subjects, and may contribute to the development of the insulin resistance/metabolic syndrome in this population.

Depression and chronic obstructive pulmonary disease (COPD) are major causes of disability. Identifying COPD patients at risk for depression would facilitate the alleviation of an important comorbidity conferring additional risk for poor outcomes. The purpose of this study was to determine the utility of a brief screening measure, the 15-item Geriatric Depression Scale (GDS-15), in detecting the mood disorders in persons with COPD. This is a cross-sectional study of 188 persons with COPD, stratified by age (65 and older versus less than 65) and COPD severity using Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging. Screening cut-points were empirically derived using threshold selection methods and receiver operating characteristic (ROC) curves were estimated. The GDS-15 was used as a screening measure and diagnoses of Major Depressive Disorder (MDD) or other mood disorders were determined using a "gold standard" standardized structured clinical interview. Of the 188 persons with COPD, 25% met criteria for any mood disorder and 11% met criteria for MDD. Optimal threshold estimations suggested a GDS cut score of 5, which yielded adequate sensitivity and specificity in detecting MDD (81% and 87%, respectively) and correctly classified 86% of participants. To detect the presence of any mood disorder, a cut score of 4 was suggested yielding sensitivity and specificity of 67% and 82%, respectively; correctly classifying 79%. These results suggest that mood disorders are relatively common among persons with COPD. The GDS-15 is a useful screening measure to identify patients at risk for depression.

Determination of HIV-1 subtype may be important in the management of HIV-infected individuals, particularly with regard to deciding the CD4 cell count at which to initiate antiretroviral therapy. Non-B subtypes, A and D, are prevalent in Uganda, and individuals infected with subtype D seem to have faster disease progression compared with those infected with subtype A. We examined the level of apoptosis in CD4+ T cells in a study cohort of volunteers infected with subtypes A and D infection. Although the levels of apoptosis in the activated CD4+ cells significantly decreased with viral suppression, CD4+ apoptosis in individuals infected with subtype D were found to be significantly higher compared with those infected with subtype A before antiretroviral treatment. Surface expression of PD-1 on CD4 cells in subtype D was substantially higher compared with that in subtype A (P = 0.03). This difference was not observed in the CD8 population (P > 0.05). Our findings suggest that the infecting HIV subtypes exert an independent influence on the disease outcome in response to antiretroviral treatment.

BACKGROUND

Patient preferences can affect colorectal cancer (CRC) screening test use. We compared utility-based preferences for alternative CRC screening tests from a stated-preference discrete-choice survey of the general population and physicians in Canada and the United States.

METHODS

General population respondents (Canada, n = 501; US, n = 1087) participated in a survey with 12 choice scenarios and 9 CRC screening test attributes. Physicians (n = 100, both Canada and US) reported expected patient preferences. We estimated relative importance of attributes using bivariate probit regression analysis and calculated willingness-to-pay for various CRC screening tests.

RESULTS

In 28 and 31% of scenarios, Canadian and US respondents, respectively, chose no screening over a hypothetical test. Canadian (45%) and US (46%) physicians expected patients to choose no screening more often. For all groups the most important attribute was sensitivity, but physicians' perception of patients' preferences are significantly different from actual preferences. Other key attributes are those related to test performance or the testing process. Fecal DNA, colonoscopy, and virtual colonoscopy were the most preferred tests by all groups, but respondents were willing-to-pay more than physicians predicted.

CONCLUSION

Physicians' perception of patients' preferences are quite different from those of the general population. However, among general population and physicians, Canadian and US preferences were similar.

The Department of Veterans Affairs (VA) National Quality Scholars Fellowship Program (VAQS) was established in 1998 as a postgraduate medical education fellowship to train physicians in new methods of improving the quality and safety of health care for veterans and the nation. The VAQS curriculum is based on adult learning theory, with a national core curriculum of face-to-face components, technologically mediated distance learning components, and a unique local curriculum that draws from the strengths of regional resources. VAQS has established strong ties with other VA programs. Fellows' research and quality improvement projects are integrated with local and regional VA leaders' priorities, enhancing the relevance and visibility of the fellows' efforts and promoting recruitment of fellows to VA positions. VAQS has enrolled 98 fellows since 1999; 75 have completed the program and 24 are currently enrolled. Fellowship graduates have pursued a variety of career paths: 17% are continuing training (most in VA), 31% hold a VA faculty/staff position, 66% are academic faculty, and 80% conduct clinical or research work related to health care improvement. Graduates have held leadership positions in VA, Department of Defense, academic medicine, and public health agencies. Combining knowledge about the improvement of health care with adult learning strategies, distance learning technologies, face-to-face meetings, local mentorship, and experiential projects has been successful in improving care in VA and preparing physicians to participate in, study, and lead the improvement of health care quality and safety.