Publications

BACKGROUND

GB virus type C (GBV-C) is transmitted by sexual or parenteral exposure and is prevalent among patients receiving blood products. GBV-C is associated with lower human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. Open questions are the presence and the direction of any causal relationship between GBV-C infection and HIV disease markers in the context of highly active antiretroviral therapy (HAART).

METHODS

We used a limited access database obtained from the National Heart, Lung, and Blood Institute's Viral Activation Transfusion Study (VATS), a randomized controlled trial of leukoreduced vs nonleukoreduced transfusions to HIV-infected transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers. Cox regression models and inverse probability of treatment weights were used to examine the association between GBV-C coinfection and mortality in the VATS cohort.

RESULTS

We found a significant reduction in mortality among GBV-C coinfected VATS subjects, after adjusting for HAART status, HIV RNA level, and CD4 cell count at baseline. Acquisition of GBV-C RNA (n = 39) was associated with lower mortality in 294 subjects who were GBV-C negative at baseline, adjusting for baseline covariates (hazard ratio = 0.22, 95% confidence interval [CI]: .08-.58) and in models in which weights were used to control for time-updated covariates (odds ratio = 0.21, 95% CI: .08-.60).

CONCLUSIONS

GBV-C viremia is associated with lower mortality, and GBV-C acquisition via transfusion is associated with a significant reduction in mortality in HIV-infected individuals, controlling for HIV disease markers. These findings provide the first evidence that incident GBV-C infection alters mortality in HIV-infected patients.

The populations in greatest need of iron supplementation are also those at greatest risk of malaria: pregnant women and young children. Iron supplementation has been shown to increase malaria risk in these groups in numerous studies, although this effect is likely diminished by factors such as host immunity, host iron status, and effective malaria surveillance and control. Conversely, the risk of anemia is increased by malaria infections and preventive measures against malaria decrease anemia prevalence in susceptible populations without iron supplementation. Studies have shown that subjects with malaria experience diminished absorption of orally administered iron, so that as a consequence, iron supplementation may have generally reduced efficacy in malarious populations. A possible mechanistic link between malaria, poor absorption of iron, and anemia is provided by recent research on hepcidin, the human iron control hormone. Our improved understanding of iron metabolism may contribute to the control of malaria and the treatment of anemia. Malaria surveillance and control are necessary components of programs to control iron deficiency and may enhance the efficacy of iron supplementation.

The suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes circadian rhythms of cells and tissues throughout the body. In SCN neurons, rhythms of clock gene expression are suppressed by manipulations that hyperpolarize the plasma membrane or lower intracellular Ca(2+). However, whether clocks in other cells also depend on membrane potential and calcium is unknown. In this study, the authors investigate the effects of membrane potential and intracellular calcium on circadian rhythms in mouse primary fibroblasts. Rhythms of clock gene expression were monitored using a PER2::LUC knockin reporter. Rhythms were lost or delayed at lower (hyperpolarizing) K(+) concentrations. Bioluminescence imaging revealed that this loss of rhythmicity in cultures was due to loss of rhythmicity of single cells rather than loss of synchrony among cells. In lower Ca(2+) concentrations, rhythms were advanced or had shorter periods. Buffering intracellular Ca(2+) by the calcium chelator 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) or manipulation of inositol triphosphate (IP(3))-sensitive intracellular calcium stores by thapsigargin delayed rhythms. These results suggest that the circadian clock in fibroblasts, as in SCN neurons, is regulated by membrane potential and Ca(2+). Changes in intracellular Ca(2+) may mediate the effects of membrane potential observed in this study.

BACKGROUND

Potentially teratogenic medications are frequently prescribed without provision of contraceptive counseling.

OBJECTIVE

To evaluate whether computerized clinical decision support (CDS) can increase primary care providers' (PCPs') provision of family planning services when prescribing potentially teratogenic medications.

DESIGN

Cluster-randomized trial conducted in one academic and one community-based practice between October of 2008 and April of 2010.

PARTICIPANTS/INTERVENTIONS

Forty-one PCPs were randomized to receive one of two types of CDS which alerted them to risks of medication-induced birth defects when ordering potentially teratogenic medications for women who may become pregnant. The 'simple' CDS provided a cautionary alert; the 'multifaceted' CDS provided tailored information and links to a structured order set designed to facilitate safe prescribing. Both CDS systems alerted PCPs about medication risk only once per encounter.

MAIN MEASURES

We assessed change in documented provision of family planning services using data from 35,110 encounters and mixed-effects models. PCPs completed surveys before and after the CDS systems were implemented, allowing assessment of change in PCP-reported counseling about the risks of medication-induced birth defects and contraception.

KEY RESULTS

Both CDS systems were associated with slight increases in provision of family planning services when potential teratogens were prescribed, without a significant difference in improvement by CDS complexity (p = 0.87). Because CDS was not repeated, 13% of the times that PCPs received CDS they substituted another potential teratogen. PCPs reported significant improvements in several counseling and prescribing practices. The multifaceted group reported a greater increase in the number of times per month they discussed the risks of medication use during pregnancy (multifaceted: +4.9 ± 7.0 vs. simple: +0.8 ± 3.2, p = 0.03). The simple CDS system was associated with greater clinician satisfaction.

CONCLUSIONS

CDS systems hold promise for increasing provision of family planning services when fertile women are prescribed potentially teratogenic medications, but further refinement of these systems is needed.

Teratogenic medications are commonly prescribed to women of reproductive age. Caring for women who may benefit from the use of teratogenic medications requires clinicians to engage patients in shared decision-making on the risks and benefits of medication use in the context of the patient's fertility goals, the implications of the patient's medical condition for a pregnancy and the risks and benefits of various contraceptive methods. Effective communication about all of these issues is essential to avoiding medication-induced birth defects. However, data suggest that such communication remains inadequate, leading some women to face unintentional exposure of a pregnancy to a teratogen, undesired pregnancy or, sometimes, the need for pregnancy termination services. This review outlines key information needed to ensure safe prescribing to women of childbearing age. It includes recommendations for changes in medical education, healthcare delivery and health policy to facilitate thoughtful prescribing and comprehensive care.

We determined the diagnostic yield of the Xpert MTB/RIF assay for tuberculosis (TB) when testing small volumes of urine from ambulatory HIV-infected patients before starting antiretroviral therapy in South Africa. Compared with a gold standard of sputum culture, the sensitivity of urine Xpert among those with CD4 cell counts of <50, 50-100, and >100 cells per microliter were 44.4%, 25.0%, and 2.7% (P = 0.001), respectively. Urine Xpert testing provides a means of rapid TB diagnosis in patients with advanced immunodeficiency and poor prognosis. These data are indicative of high rates of TB dissemination and renal involvement in this clinical population.

BACKGROUND

The Centers for Medicare and Medicaid Services is considering developing a 30-day ischemic stroke hospital-level mortality model using administrative data. We examined whether inclusion of the National Institutes of Health Stroke Scale (NIHSS), a measure of stroke severity not included in administrative data, would alter 30-day mortality rates in the Veterans Health Administration.

METHODS AND RESULTS

A total of 2562 veterans admitted with ischemic stroke to 64 Veterans Health Administration Hospitals in the fiscal year 2007 were included. First, we examined the distribution of unadjusted mortality rates across the Veterans Health Administration. Second, we estimated 30-day all-cause, risk standardized mortality rates (RSMRs) for each hospital by adjusting for age, sex, and comorbid conditions using hierarchical models with and without the inclusion of the NIHSS. Finally, we examined whether adjustment for the NIHSS significantly changed RSMRs for each hospital compared with other hospitals. The median unadjusted mortality rate was 3.6%. The RSMR interquartile range without the NIHSS ranged from 5.1% to 5.6%. Adjustment with the NIHSS did not change the RSMR interquartile range (5.1%-5.6%). Among veterans ≥65 years, the RSMR interquartile range without the NIHSS ranged from 9.2% to 10.3%. With adjustment for the NIHSS, the RSMR interquartile range changed from 9.4% to 10.0%. The plot of 30-day RSMRs estimated with and without the inclusion of the NIHSS in the model demonstrated overlapping 95% confidence intervals across all hospitals, with no hospital significantly below or above the mean-unadjusted 30-day mortality rate. The 30-day mortality measure did not discriminate well among hospitals.

CONCLUSIONS

The impact of the NIHSS on RSMRs was limited. The small number of stroke admissions and the narrow range of 30-day stroke mortality rates at the facility level in the Veterans Health Administration cast doubt on the value of using 30-day RSMRs as a means of identifying outlier hospitals based on their stroke care quality.