Publications

We assessed laboratory monitoring after combination antiretroviral therapy initiation among 3678 patients in a large US multisite clinical cohort, censoring participants at last clinic visit, combination antiretroviral therapy change, or 3 years. Median days (interquartile range) to first hematologic, hepatic, renal, and lipid tests were 30 (18-53), 31 (19-56), 33 (20-59), and 350 (96-1106), respectively. At 1 year, approximately 80% received more than 2 hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received 1 or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities.

OBJECTIVE

Studies of the association between transportation barriers and HIV-related health outcomes have shown both positive and negative effects, possibly because a reliable, validated measure of transportation barriers has not been identified.

DESIGN

Prospective cohort study of HIV-infected patients in rural Uganda.

METHODS

Participants were enrolled from the HIV clinic at the regional referral hospital in Mbarara, Uganda as part of the Uganda AIDS Rural Treatment Outcomes (UARTO) Study. We collected the following measures of transportation barriers to HIV clinic: global positioning systems (GPS)-tracked distance measured by driving participants to their homes along their typical route; straight-line GPS distance from clinic to home, calculated with the Great Circle Formula; self-reported travel time; and self-reported travel cost. We assessed inter-measure agreement using linear regression, correlation coefficients and κ statistics (by measure quartile) and validated measures by fitting linear regression models to estimate associations with days late for clinic visits.

RESULTS

One hundred and eighty-eight participants were tracked with GPS. Seventy-six percent were women, with a median age of 40 years and median CD4 cell count of 193 cells/μl. We found a high correlation between GPS-based distance measures (β=0.74, P<0.001, R²=0.92, κ=0.73), but little correlation between GPS-based and self-reported measures (all R²≤0.4). GPS-based measures were associated with days late to clinic (P<0.001); but neither self-reported measure was associated (P>0.85).

CONCLUSION

GPS-measured distance to clinic is associated with HIV clinic absenteeism and should be prioritized over self-reported measures to optimally risk-stratify patients accessing care in rural, resource-limited settings.

BACKGROUND

Indoleamine 2,3-dioxygenase, catalyzing tryptophan (Trp) metabolism through the kynurenine (Kyn) metabolic pathway, plays important roles in immune suppression and the CNS. In this article, we report a simple, rapid and specific LC-MS/MS method for accurate determination of Kyn and Trp concentrations in human plasma from HIV-infected patients.

RESULTS

The human plasma sample (100 µl) was mixed with Kyn-d4 and Trp-d5 internal standards and then precipitated with trifluoroacetic acid. The supernatant was directly analyzed by LC-MS/MS. The assay using surrogate matrix calibrators was validated for precision, accuracy, matrix effect, extraction efficiency and stability. Some assay validation issues for endogenous substance bioanalysis using an LC-MS/MS method are discussed.

CONCLUSION

A simple, specific and reproducible LC-MS/MS method has been developed and validated for measuring Kyn and Trp in human plasma samples.

A considerable number of women with breast cancer are diagnosed during their reproductive years. In the short period of time in which newly diagnosed women will need to make decisions about surgical options and adjuvant therapy, younger women with breast cancer also face the potential impairment or complete loss of their fertility. The preservation of fertility should therefore be an integral consideration in the choice of breast cancer therapy. Preserving ovarian function is particularly challenging for women with estrogen receptor-positive tumors, as the suppression of ovarian function has been shown to be beneficial therapy with regard to breast cancer outcomes. The current emerging recommendations of hormonal therapy extending to a 10-year period will likely further impact the timing of any subsequent pregnancy or require an interruption in hormonal therapy. To optimally counsel patients on how to best weigh the risks and benefits of each intervention, both the care provider and the patient must understand the options and the likelihood of their success. Here we summarize the current challenges and options for women diagnosed with breast cancer who wish to preserve their fertility.

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with pulmonary vasculopathy.

OBJECTIVE

The purpose of this study was to determine whether sildenafil improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction.

METHODS

The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF, defined by carbon monoxide diffusing capacity < 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafil treatment, and changes in 6MWD, St. George's Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks.

RESULTS

The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafil experienced less decrement in 6MWD (99.3 m; P = .01) and greater improvement in SGRQ (13.4 points; P = .005) and EuroQol visual analog scores (17.9 points; P = .04) than subjects receiving placebo. In the subgroup with RVH, sildenafil was not associated with change in 6MWD (P = .13), but was associated with greater relative improvement in SGRQ (14.8 points; P = .02) vs subjects receiving placebo. Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36.

CONCLUSIONS

Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafil also improves quality of life in subjects with RVH and RVSD.

OBJECTIVE

Evaluate effect of gender role attitudes on tobacco and alcohol use among Argentinean girls.

METHOD

Cross-sectional survey of 10th grade students attending 27 randomly selected schools in Jujuy, Argentina. Questions about tobacco and alcohol use were adapted from global youth surveys. Five items with 5-point response options of agreement-disagreement assessed attitude towards egalitarian (higher score) gender roles.

RESULTS

2133 girls, aged 13-18 years, 71% Indigenous, 22% mixed Indigenous/European, and 7% European responded. Of these, 60% had ever smoked, 32% were current smokers, 58% ever drinkers, 27% drank in previous month, and 13% had ≥5 drinks on one occasion. Mean response to the gender role scale was 3.49 (95% Confidence Intervals = 3.41-3.57) out of 5 tending toward egalitarian attitudes. Logistic regression models using the gender role scale score as the main predictor and adjusting for demographic and social confounders showed that egalitarian gender role was associated with ever smoking (Odds Ratio = 1.25; 95% Confidence Intervals 1.09-1.44), ever drinking (Odds Ratio = 1.24; 95% Confidence Intervals 1.10-1.40), drinking in prior month (Odds Ratio = 1.21; 95% Confidence Intervals 1.07-1.37) and ≥5 drinks on one occasion (Odds Ratio = 1.15; 95% Confidence Intervals 1.00-1.33), but was not significant for current smoking.

CONCLUSION

Girls in Jujuy who reported more egalitarian gender role attitudes had higher odds of smoking or drinking.

OBJECTIVES

This study sought to perform a systematic review and meta-analysis to understand the role of stress cardiac magnetic resonance imaging (CMR) in assessing cardiovascular prognosis in patients with known or suspected coronary artery disease (CAD).

BACKGROUND

Although stress CMR is excellent for the diagnosis of obstructive CAD, the prognostic value of stress CMR has been less well described.

METHODS

PubMed, Cochrane CENTRAL, and metaRegister of Controlled Trials were searched for stress CMR studies with >6 months of prognostic data. Primary endpoints were cardiovascular death, myocardial infarction (MI), and a composite outcome of cardiovascular death or MI during follow-up. Summary effect estimates were generated with random-effects modeling, and annualized event rates were assessed.

RESULTS

Nineteen studies (14 vasodilator, 4 dobutamine, and 1 that used both) involved a total of 11,636 patients with a mean follow-up of 32 months. Patients had a mean age of 63 ± 12 years, 63% were male, and 26% had previous MI; mean left ventricular ejection fraction was 61 ± 12%; and late gadolinium enhancement was present in 29% and ischemia in 32%. Patients with ischemia had a higher incidence of MI (odds ratio [OR]: 7.7; p < 0.0001), cardiovascular death (OR: 7.0; p < 0.0001), and the combined endpoint (OR: 6.5; p < 0.0001) compared with those with a negative study. The combined outcome annualized events rates were 4.9% for a positive versus 0.8% for a negative stress CMR (p < 0.0001), 2.8% versus 0.3% for cardiovascular death (p < 0.0001), and 2.6% versus 0.4% for MI (p < 0.0005). The presence of late gadolinium enhancement was also significantly associated with a worse prognosis.

CONCLUSIONS

A negative stress CMR study is associated with very low risk of cardiovascular death and MI. Stress CMR has excellent prognostic characteristics and may help guide risk stratification of patients with known or suspected CAD.