Cost-Effectiveness of Maraviroc for Antiretroviral Treatment-Experienced HIV-infected Individuals in Mexico

ObjectiveMaraviroc is the first approved drug in a new class of antiretrovirals, the CCR5 antagonists. The objective of this study was to predict the long-term clinical impact and cost-effectiveness of maraviroc in treatment-experienced adults with HIV/AIDS in Mexico.MethodsThe AntiRetroviral Analysis by Monte Carlo Individual Simulation (ARAMIS) model was adapted to the Mexican context to predict clinical and economic outcomes of treating with optimized background therapy (OBT) versus testing for viral tropism status and treating with OBT ± maraviroc accordingly in treatment-experienced adults in Mexico. Baseline characteristics and efficacy were from the MOTIVATE trials' screening cohort. Costs and population mortality data were specific to Mexico. Results were reported from the perspective of health care payers in 2008 Mexican pesos (converted to 2008 US$ in parentheses).ResultsCompared to treatment with OBT alone, treatment with OBT ± maraviroc contingent on tropism test result increased projected undiscounted life expectancy and discounted quality-adjusted life expectancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life years (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). The resultant incremental cost-effectiveness ratio (ICER) was $453,978 (US$42,429) per QALY gained. The ICER was somewhat lower when maraviroc was modeled in individuals susceptible to ≤2 components of OBT ($407,329; US$38,069), while the ICER was higher in individuals susceptible to ≥3 OBT components ($718,718; US$67,171).ConclusionIn treatment-experienced individuals with HIV/AIDS in Mexico, maraviroc may be cost-effective, particularly in individuals with limited options for active antiretroviral therapy (ART).     

Comparison of choroidal thickness in systemic hypertensive subjects with healthy individuals by spectral domain optical coherence tomography

Purpose:The purpose of the study was to compare the choroidal thickness in normal population and hypertensive patients and to assess the possible effect of hypertension on choroidal thickness using Spectral Domain Optical Coherence Tomography (SD-OCT).Methods:This was a comparative cross-sectional study. A total of 68 eyes of 34 individuals in the age group of 40–60 years were included in both the hypertensive group and control group. Individuals with refractive error beyond ± 3 D and posterior segment pathology were excluded. The choroidal thickness was measured at the sub-foveal region, 500 μm nasal and 500 μm temporal to the fovea on SD-OCT with enhanced depth imaging (EDI) mode. Systolic blood pressure (SBP), Diastolic blood pressure (DBP), and Mean arterial pressure (MAP) were recorded in all individuals. Duration of hypertension was also noted in hypertensive individuals.Results:The choroidal thickness at all locations was significantly lower in the hypertensive group (subfoveal, nasal, temporal and mean choroidal thickness 253.24 ± 63.96 μm, 249.35 ± 63.57 μm, 250.01 ± 63.37 μm, 250.87 ± 63.38 μm, respectively) as compared to the control group (subfoveal, nasal, temporal and mean choroidal thickness 301.25 ± 55.79 μm, 298.97 ± 57.07 μm, 299.49 ± 55.06 μm, 299.90 ± 55.50 μm, respectively). The choroidal thickness in the hypertensive group also had a significant negative correlation with the SBP (Spearman correlation coefficient, rho = –0.35, P = 0.003) and the duration of hypertension (rho = -0.25, P = 0.037).Conclusion:The study demonstrated decreased choroidal thickness in systemic hypertensive subjects as compared to age-matched healthy individuals. The choroidal thickness in hypertensive subjects also had a significant but weak negative correlation with SBP and duration of hypertension.     

Differential expression of CD14-dependent and independent pathways for chemokine induction regulates neutrophil trafficking in infection

Previous studies have shown that CD14(-/-) mice are resistant to peritoneal infection with some clinical isolates of Escherichia coli and that this resistance is accompanied by an enhanced ability to clear the bacteria; in contrast, normal mice expressing CD14 fail to clear the bacteria, causing severe sepsis and death. The enhanced clearance in CD14(-/-) mice is dependent on early neutrophil recruitment to the local foci of infection in the PC. The studies described show that neutrophil recruitment in CD14(-/-) mice occurs as a result of the local induction of the CXCL1 and CXCL2 chemokines, KC and MIP-2. Although local induction of these chemokines also occurs in normal mice, their effects on neutrophil recruitment to the PC appear to be counterbalanced by very high levels of these chemokines in the blood of normal, but not CD14(-/-), mice. Neutrophil recruitment to the PC is also inhibited in normal mice in response to LPS, which also induces high chemokine levels in the blood of normal, but not CD14(-/-), mice. However, MPLA, a monophosphorylated derivative of LPS, is able to induce early neutrophil recruitment in normal mice; this is because MPLA, unlike LPS or E. coli, induces MIP-2 and KC in the PC but not in the blood of normal mice. The pretreatment of normal mice with MPLA is able to protect them from a lethal E. coli infection. Thus, stimulation of a local CD14-independent chemokine induction pathway without triggering a systemic CD14-dependent chemokine pathway can protect against severe E. coli infections.     

Death within 48 hours of admission to the emergency department: the value of autopsy

OBJECTIVE: To identify factors that contribute to patient death within 48 hours of admission to the emergency department. MATERIALS AND METHODS: A retrospective study of the patients who died within 48 hours of admission to the emergency department, from the years 2000 to 2003. The antemortem diagnosis and postmortem diagnosis were compared. RESULTS: A total of 189 autopsies were performed. The mean age at death for men (41.4 years) was lower than that for women (48.6) (p = 0.02). In both men and women, cardiac system involvement was the leading cause of death (27.5%), with myocardial infarction at 21.2%. The other common causes of death for both genders were blunt trauma (20.1%), intoxication with alcohol and/or other drugs (13.8%), penetrating trauma (gunshot or stab injuries) (13.2%), pulmonary thromboembolism (7.9%), and death caused by other respiratory causes (7.4%). Death caused by pulmonary thromboembolism was more common in women, whereas death caused by strokes, burns, and penetrating trauma were seen almost exclusively in men. CONCLUSIONS: Our study found a considerable concordance between the presumed antemortem cause of death and the postmortem findings. Although the mean age of death caused by myocardial infarction in our study was 52.45 years, MI caused a significant number of deaths among adults younger than 40 years of age.