Publications

BACKGROUND

For patients with compensated cirrhosis, transcatheter arterial embolization with and without additive chemotherapy has been shown to improve survival. The aim of this study was to compare periprocedural complications in a population with hepatitis C virus-related hepatocellular carcinoma to evaluate for differences in complications by severity of liver disease.

METHODS

Patients with unresectable hepatocellular carcinoma treated by transcatheter arterial embolization with or without additive chemotherapy procedures from 2003 to 2006 were retrospectively reviewed and compared by Child-Pugh (CP) class. A total of 141 embolizations were done in 76 patients.

RESULTS

Complication rates were seen in 27% of CP class A and 17% of CP class B patients. There was no significant difference in the grade of complications between the 2 groups or between procedure types. Survival rate was dependent on the degree of liver dysfunction (3-year CP class A, 49%; CP class B, 13%; P = .0048).

CONCLUSION

Embolization procedures to treat hepatitis C virus-related hepatocellular carcinoma can be performed safely with low morbidity and mortality rates, even in patients with a compromised hepatic reserve.

OBJECTIVES

To determine the prevalence of free medication sample use in the United States and analyze the effects of socioeconomic status and drug safety actions.

DESIGN

Cross-sectional study.

SETTING

United States from 1999 to 2005.

PARTICIPANTS

Survey respondents representative of the civilian noninstitutionalized population.

INTERVENTION

Analysis of data from the Medical Expenditure Panel Survey, a nationally representative longitudinal household survey.

MAIN OUTCOME MEASURES

Identification of a medication as being provided as a sample at least once during a study year.

RESULTS

An annual average of 5.1% (range 4.4% in 2005 to 5.8% in 2002) of all prescription medications were provided as a sample at least once during a year, with 18.3% of all Americans who received at least one prescription drug receiving at least one drug as a sample. On multivariate analysis, sample use was greater among young (18-30 years) non-Hispanic whites and the uninsured but had minimal independent association with income. The proportion of sample use among users of hormone replacement therapy and cyclooxygenase-2 inhibitors remained relatively constant even as total use of these drugs declined after Food and Drug Administration regulatory action.

CONCLUSION

Use of medication samples is common in the U.S. population. After adjusting for health insurance, sample use was not associated with income and samples were less frequently provided to racial/ethnic minorities and to the elderly. The putative economic benefits of free samples do not appear to go to patients with the greatest financial need. Drug regulatory actions did not have a disproportionate effect on provision of drugs as samples.

BACKGROUND

Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population.

METHODS

In a cohort of HIV-infected ART-naive and -ineligible Ugandan children older than 1 year, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan-Meier survival analysis and multivariate Cox proportional-hazards modeling.

RESULTS

Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by World Health Organization stage 3/4 event (n = 22), death (n = 3), or World Health Organization-defined CD4 threshold for ART initiation (n = 12). Significant univariate predictors were CD4% [hazard ratio (HR) = 2.0 per 10% decrease, P = 0.005], HIV RNA level (HR = 2.4 per log10 increase, P = 0.002), male gender (HR = 2.0, P = 0.04), age < 3 years (HR = 3.7, P = 0.001), CD4 activation (%CD4+ CD38+ HLADR+) (HR = 1.6 per 10% increase, P = 0.05), and CD8 activation (%CD8+ CD38+ HLADR+) (HR = 1.3 per 10% increase, P = 0.05] (HR = 1.3, P = 0.5). In multivariate analysis, CD4% (HR = 2.0, P = 0.034), HIV RNA level (HR = 1.8, P = 0.013), and age < 3 years (HR = 3.0, P = 0.008) were independently predictive. Children with HIV RNA >10 copies per milliliter and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years).

CONCLUSIONS

Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART per WHO 2006 guidelines.

In resource-limited settings--where a massive scale-up of HIV services has occurred in the last 5 years--both understanding the extent of and improving retention in care presents special challenges. First, retention in care within the decentralizing network of services is likely higher than existing estimates that account only for retention in clinic, and therefore antiretroviral therapy services may be more effective than currently believed. Second, both magnitude and determinants of patient retention vary substantially and therefore encouraging the conduct of locally relevant epidemiology is needed to inform programmatic decisions. Third, socio-structural factors such as program characteristics, transportation, poverty, work/child care responsibilities, and social relations are the major determinants of retention in care, and therefore interventions to improve retention in care should focus on implementation strategies. Research to assess and improve retention in care for HIV-infected patients can be strengthened by incorporating novel methods such as sampling-based approaches and a causal analytic framework.

OBJECTIVE

To determine the association of inflammatory markers, fibrinogen, and C-reactive protein (CRP), with 5-year mortality risk.

METHODS

Vital status was ascertained in 922 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. Multivariable logistic regression estimated odds ratios after adjustment for demographic, cardiovascular, and HIV-related factors.

RESULTS

Over a 5-year period, HIV-infected participants with fibrinogen levels in the highest tertile (>406 mg/dL) had 2.6-fold higher adjusted odds of death than those with fibrinogen in the lowest tertile (<319 mg/dL). Those with high CRP (>3 mg/L) had 2.7-fold higher adjusted odds of death than those with CRP <1 mg/L. When stratified by CD4 count category, fibrinogen (as a linear variable) remained independently associated [odds ratio (95% confidence intervals)] per 100 mg/dL increase in fibrinogen: 1.93 (1.57 to 2.37); 1.43 (1.14 to 1.79); 1.43 (1.14 to 1.81); and 1.30 (1.04 to 1.63) for CD4 <200, 200-350, >350 to 500, and >500 cells per microliter, respectively. Higher CRP also remained associated with higher odds of death overall and within each CD4 subgroup.

CONCLUSIONS

Fibrinogen and CRP are strong and independent predictors of mortality in HIV-infected adults. Our findings suggest that even in those with relatively preserved CD4 counts >500 cells per microliter, inflammation remains an important risk factor for mortality. Further investigation should determine whether interventions to reduce inflammation might decrease mortality risk in HIV-infected individuals.

BACKGROUND

Some HIV protease inhibitors (PIs), including full-dose ritonavir (800 mg) and ritonavir-boosted lopinavir, acutely induce insulin resistance in the absence of HIV infection and changes in body composition. Boosting dose ritonavir (100-200 mg) is the most commonly prescribed PI, yet its effects on glucose metabolism have not been described in the absence of another PI.

METHODS

In this randomized, double-blind, cross-over study, a single dose of ritonavir 200 mg or placebo was given to healthy HIV-seronegative volunteers before assessment of insulin sensitivity by euglycemic hyperinsulinemic clamp.

RESULTS

Boosting dose ritonavir had no effect on insulin-mediated glucose disposal (M/I, placebo: 8.59 ± 0.83 vs. ritonavir: 8.51 ± 0.64 mg/kg per minute per μU/mL insulin, P = 0.89).

CONCLUSIONS

A single boosting dose of ritonavir does not alter insulin sensitivity, suggesting lopinavir is likely responsible for the induction of insulin resistance demonstrated in prior short-term studies of lopinavir/ritonavir. There is a dose-dependent effect of ritonavir on insulin sensitivity.

Normal anatomic variation, study design, external factors, and tissue characteristics can all influence the manifestation of structures on magnetic resonance images (MRI). For the purpose of this review, imaging artifacts are considered to be nonpathologic abnormalities resulting from study design, intrinsic tissue characteristics, or external factors, while MRI pseudolesions are due to normal anatomic variation. Awareness of imaging artifacts and pseudolesions, as well as normal anatomic structures, is important when determining pathologic vs. normal or clinically insignificant abnormalities. The purpose of this report is to examine the literature to compile a review of selected artifacts and pseudolesions that are commonly encountered when imaging the canine and feline brain.

The human ATP-binding cassette (ABC) transporter superfamily consists of 48 integral membrane proteins that couple the action of ATP binding and hydrolysis to the transport of diverse substrates across cellular membranes. Defects in 18 transporters have been implicated in human disease. In hundreds of cases, disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs). The functional impact of the majority of ABC transporter nsSNPs has yet to be experimentally characterized. Here, we combine experimental mutational studies with sequence and structural analysis to describe the impact of nsSNPs in human ABC transporters. First, the disease associations of 39 nsSNPs in 10 transporters were rationalized by identifying two conserved loops and a small α-helical region that may be involved in interdomain communication necessary for transport of substrates. Second, an approach to discriminate between disease-associated and neutral nsSNPs was developed and tailored to this superfamily. Finally, the functional impact of 40 unannotated nsSNPs in seven ABC transporters identified in 247 ethnically diverse individuals studied by the Pharmacogenetics of Membrane Transporters consortium was predicted. Three predictions were experimentally tested using human embryonic kidney epithelial (HEK) 293 cells stably transfected with the reference multidrug resistance transporter 4 and its variants to examine functional differences in transport of the antiviral drug, tenofovir. The experimental results confirmed two predictions. Our analysis provides a structural and evolutionary framework for rationalizing and predicting the functional effects of nsSNPs in this clinically important membrane transporter superfamily.