In the present study, we investigated genetic divergence between complete autologous HIV-1 env genes amplified directly from plasma of two anti-retroviral naïve, slow progressing Indian patients with broad neutralizing antibody response. All the envelopes (Env) clones obtained from one patient (LT1) belonged to subtype C; the second patient (LT5) harbored quasispecies comprising of pure B, C and B/C recombinants with distinct breakpoints indicative of dual infection with genetically distinct strains. Further characterization of these Envs would provide insights to the biological properties under strong humoral immune response.

Background: The potential to save money within a short time frame provides a more compelling "business case" for quality improvement than merely demonstrating cost-effectiveness. Our objective was to demonstrate the potential for cost savings from improved control in patients anticoagulated for atrial fibrillation.

Methods and Results: Our population consisted of 67 077 Veterans Health Administration patients anticoagulated for atrial fibrillation between October 1, 2006, and September 30, 2008. We simulated the number of adverse events and their associated costs and utilities, both before and after various degrees of improvement in percent time in therapeutic range (TTR). The simulation had a 2-year time horizon, and costs were calculated from the perspective of the payer. In the base-case analysis, improving TTR by 5% prevented 1114 adverse events, including 662 deaths; it gained 863 quality-adjusted life-years and saved $15.9 million compared with the status quo, not accounting for the cost of the quality improvement program. Improving TTR by 10% prevented 2087 events, gained 1606 quality-adjusted life-years, and saved $29.7 million. In sensitivity analyses, costs were most sensitive to the estimated risk of stroke and the expected stroke reduction from improved TTR. Utilities were most sensitive to the estimated risk of death and the expected mortality benefit from improved TTR.

Conclusions: A quality improvement program to improve anticoagulation control probably would be cost-saving for the payer, even if it were only modestly effective in improving control and even without considering the value of improved health. This study demonstrates how to make a business case for a quality improvement initiative

Abstract HIV-2 group A is predominant in different parts of the world, especially Africa, Portugal, Spain, France, the United Kingdom, the United States, Korea, and India. Among the Asian countries, India accounts for about 95% of all HIV-2 infections. The prevalence of HIV-2 has been reported from various states of India such as Maharashtra, Goa, Tamil Nadu, West Bengal, and Uttar Pradesh. In the present study, we analyzed transmembrane region (gp36) sequences of 10 HIV-2 group A Indian strains, isolated from Indian HIV-2-seropositive individuals. HIV Blast analysis for the 1.0-Kb region of the gp36 transmembrane region has shown that all these sequences belong to HIV-2 group A. Phylogenetic analysis indicated that the sequences cluster with HIV-2 group A sequences of Cameroon and Senegal. The epitope found at position 645-656 (YELQKLNSWDVF), previously reported as a broadly neutralizing determinant, was very well conserved in all 10 study sequences. The percentage similarity between Indian and South African HIV-2 group A gp36 sequences was 90% (range 86-100, SD 2.8) and with other nonsubtype A clades was 84% (range 77-100, SD 6.06) indicating overall less variability among the reported HIV-2 sequences. Similarly, the consensus amino acid sequences of the envelope transmembrane region of HIV-1 (gp41) and HIV-2 (gp36) is quite synonymous, indicating 87% similarity; however, limited information is available about the gp36 transmembrane region of the prevalent HIV 2 group A Indian strain. The rate of synonymous substitutions reported in the gp105 region was significantly higher, suggesting lower virulence of HIV-2, which does translate into a lower rate of evolution, while the dN/dS ratio for the gp36 transmembrane region was less than one, indicating its conservation and significance (p<0.05) in structural and functional constraints.

Abstract

Rural status of patients may impact health before and after pediatric LT. We used UI codes published by the USDA to stratify patients as urban or rural depending county residence. A total of 388 patients who had LT and who met criteria were included. Rejection, PTLD, and survival were used as primary outcome measures of post-LT health. UNOS Status 1 and PELD/MELD scores >20 were used as secondary outcome measures of poorer pre-LT health. Logistic regression models were run to determine associations. We did not find any statistically significant differences in pre- or post-LT outcomes with respect to rurality. Among rural patients, there was a general trend for decreased incidence of rejection (25.0% vs. 33.4%; OR 0.64, 95% CI 0.29-1.44), increased risk of PTLD (5.6% vs. 3.4%; OR 1.86, 95% CI 0.36-3.31), and decreased survival (OR 0.85, 95% CI 0.34-2.13) after LT. Rural patients also tended to be sicker at the time of LT than patients from urban areas, with increased proportion of Status 1 (OR 1.17, 95% CI 0.51-2.70) and PELD/MELD scores >20 (OR 1.20, 95% CI 0.59-2.45). From a single center experience, we conclude that rurality did not significantly affect health outcomes after LT, although a larger study may validate the general trends that rural patients may have decreased rejection, increased PTLD, and mortality, and be in poorer health at the time of LT.

BACKGROUND: The recent RV144 clinical trial showed that an ALVAC/AIDSVAX prime-boost  HIV vaccine regimen may confer partial immunity in recipients and reduce transmission by 31%. Trial data suggest that efficacy may initially exceed 70% but decline over the following 3.5 years. Estimating the potential health benefits associated with a one-time vaccination campaign, as well as the projected benefits of repeat booster vaccination, may inform future HIV vaccine research and licensing decisions.

METHODS: We developed a mathematical model to project the future course of the HIV epidemic in the United States under varying HIV vaccine scenarios. The model accounts for disease progression, infection transmission, antiretroviral therapy, and HIV-related morbidity and mortality. We projected HIV prevalence and incidence over time in multiple risk groups, and we estimated quality-adjusted life years (QALYs) and costs over a 10-year time horizon. We used an exponentially declining efficacy curve fit to trial data, and we assumed subsequent vaccine boosters confer similar immunity. Variations in vaccine parameters were examined in sensitivity analysis.

RESULTS: Under existing HIV prevention and treatment efforts, an estimated 590,000 HIV infections occur over 10 years. One-time vaccination achieving 60% coverage of adults could prevent 9.8% of projected new infections over 10 years (and prevent 34% of new infections in the first year) and cost approximately $91,000/QALY gained relative to the status quo, assuming a vaccination price of $500. Targeted vaccination of high-risk groups results in net cost savings for vaccines costing less than $750. One-time vaccination of 60% of all adults coupled with three-year boosters only for men who have sex with men and injection drug users could prevent 21% of infections for $81,000/QALY gained relative to vaccination of high-risk groups only. A program attaining 90% vaccination coverage prevents 15% of new HIV cases over 10 years (and approximately50% of infections in the first year).

CONCLUSIONS: A partially effective HIV vaccine with effectiveness similar to that observed in the RV144 trial would provide large health benefits in the United States and could meet conventionally accepted cost-effectiveness thresholds. Strategies that target high-risk groups are most efficient, but broader strategies provide greater total population health benefit.

Parenteral nutrition (PN), containing fat emulsions derived from soybean, has been implicated in the progression of PN-associated liver disease and cholestasis, particularly in infants with short bowel syndrome. Clinical use of Omegaven, a parenteral fish-oil emulsion, has been shown in recent studies to be a promising therapy to reverse liver disease and cholestasis. This review summarizes the rationale, relevant clinical investigations and future direction of Omegaven therapy for PN-dependent infants.