Publications

In 2008, diagnosis and investigation of 2 multidrug-resistant tuberculosis cases with matching genotypes led to identification of an outbreak among foreign-born persons who performed short-term seafood production work in Alaska during 2006. Tuberculosis control programs should consider the possibility of domestic transmission even among foreign-born patients.

BACKGROUND

Within the Veterans Health Administration (VHA), approximately 6000 veterans are hospitalized with acute ischemic stroke annually. We examined the use and misuse of thrombolytic therapy with tissue plasminogen activator (tPA) in a national sample of veterans who were admitted to a VHA Medical Center (VAMC) with acute ischemic stroke.

METHODS

Medical record reviews were conducted on 5000 acute stroke patients who were admitted to a VAMC in 2007. Patients were defined as eligible to receive tPA if they arrived at the hospital within 3 hours of stroke symptom onset and had no contraindications to tPA. We compared eligible patients who received tPA to those who did not and examined the distribution of eligible patients across the 129 VAMCs included in this study.

RESULTS

Among the 3931 ischemic stroke patients, 174 (4.4%) were eligible for tPA. Among the 135 patients who arrived within 2 hours of symptom onset which allowed adequate time for testing and evaluation, 19 (14.1%) received tPA. An additional 11 patients received tPA but did not meet eligibility criteria. Eligible patients receiving tPA were similar to eligible patients not receiving tPA in terms of clinical conditions and time to brain imaging. Among the 30 patients that received tPA, 5 (16.6%) received the wrong dose. Among the 85 VAMCs that received ≥1 eligible patient, on average 2.3 patients were eligible for tPA annually.

CONCLUSIONS

Relatively few eligible veterans receive thrombolysis across the VHA system. Strategies to improve thrombolysis delivery will have to account for the low annual volume of eligible stroke patients cared for at individual VAMCs.

Tamoxifen decreases breast cancer recurrence, mortality, and breast cancer risk in high-risk women. Despite these proven benefits, tamoxifen use is often limited due to side effects. We identified predictors of tamoxifen-induced side effects based on clinical variables and serum tamoxifen metabolite biomarkers in a cross-sectional study of patients taking tamoxifen. We enrolled 241 women and collected data on demographics, tamoxifen use and side effects, as well as potential clinical and serum predictors. We used logistic regression models and adjusted for age, body mass index, ethnicity, education, prior post-menopausal hormone therapy (HT), tamoxifen duration, and endoxifen levels to identify factors associated with side effects. Common tamoxifen attributed side effects were hot flashes (64%), vaginal dryness (35%), sleep problems (36%), weight gain (6%), and depression, irritability or mood swings (6%). In multi-variate models, tamoxifen duration, age, prior post-menopausal HT, and endoxifen levels all predicted side effects. Women who had been on tamoxifen for >12 months were less likely to report side effects (OR 0.15, 95% CI 0.04-0.58) or severe side effects (OR 0.05, 95% CI 0.005-0.58) compared to women on tamoxifen for <12 months. Compared to women younger than 50, women who were age 60-70 and older than 70 were less likely to report side effects (OR 0.22, 95% CI 0.03-1.35; OR 0.13, 95% CI 0.01-0.99; respectively). Women who previously took post-menopausal HT were more likely to report severe side effects. Women with higher endoxifen levels were more likely to report side effects (OR 1.67, 95% CI 1.01-2.77 per standard deviation increase in endoxifen). Clinicians should consider closely monitoring adherence in women taking tamoxifen, especially in younger women, and women who previously took HT. The association between endoxifen levels and side effects is consistent with the data that suggest that endoxifen is the most highly active metabolite of tamoxifen.

The alveolar epithelium serves as a barrier to the entry of potential respiratory pathogens. Alveolar Type II (TII) cells have immunomodulatory functions, but whether Type I (TI) cells, which comprise approximately 95% of the alveolar epithelium, also play a role in immunity is unknown. Because the renin-angiotensin system (RAS) is emerging as an important mediator of inflammation, and angiotensin-converting enzyme 2 (ACE2), an element of the RAS, has been implicated in lung injury, we hypothesize that TI cells can produce cytokines in response to LPS stimulation, and that this inflammation can be modulated by the RAS. Alveolar TI cells were isolated from adult Sprague-Dawley rat lungs that had been injured with an intratracheal instillation of LPS. PCR was performed to determine whether TI cells expressed transcripts for TNF-α, IL-6, or IL-1β at baseline and after lung injury. Immunocytochemical and protein analysis detected angiotensin II (Ang II) and ACE2, as well as angiotensin Type 1 receptor (AT1R) and Type 2 receptor (AT2R), in TI cells. To separate cell-specific responses, primary TI cells were isolated, cultured, and exposed to LPS, Ang II, or specific inhibitors of AT1R or AT2R. Cytokine production was assayed by ELISA. LPS stimulated the production of all cytokines, whereas ACE2 and losartan, an AT1R inhibitor, blocked elements of the LPS-induced cytokine response. Primary TI cells produce cytokines when treated with LPS, contain important components of the RAS, and can modulate LPS-induced cytokine production via the RAS, suggesting a role for TI cells in the innate immune response of the lung.

BACKGROUND

Despite improvements in survival with human immunodeficiency virus (HIV) infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with the development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals and compare ESRD risk by estimated glomerular filtration rate (eGFR) and proteinuria levels.

STUDY DESIGN

Retrospective cohort study.

SETTING & PARTICIPANTS

22,156 HIV-infected veterans without pre-existing ESRD receiving health care in the Veterans' Affairs medical system between 1996 and 2004.

PREDICTORS

Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin <3.5 mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and eGFR were identified using the Veterans' Affairs electronic record system.

OUTCOMES

ESRD was ascertained by the US Renal Data System.

RESULTS

366 cases of ESRD occurred, corresponding to 3 cases/1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5-2.4), diabetes (HR, 1.7; 95% CI, 1.3-2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7-2.7) were associated independently with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/μL (HR, 1.5; 95% CI, 1.2-2.0), HIV viral load ≥30,000 copies/mL (HR, 2.0; 95% CI, 1.5-2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5-2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8-2.5). Compared with persons without chronic kidney disease, defined as eGFR >60 mL/min/1.73 m(2) and no proteinuria, lower eGFR and higher proteinuria categories were associated jointly with exponentially higher ESRD rates, ranging from 6.6 events/1,000 person-years for persons with urine protein excretion of 30-100 mg/dL and eGFR >60 mL/min/1.73 m(2) to 193 events/1,000 person-years for persons with urine protein excretion ≥300 mg/dL and eGFR <30 mL/min/1.73 m(2).

LIMITATIONS

Results may not be generalizable to female and nonveteran populations.

CONCLUSIONS

In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for chronic kidney disease staging is most effective for stratifying the risk of ESRD.