Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support

Ex-Ante PLM Misfit Analysis Methodology: A Cognitive Fit Approach

Commercial off-the-shelf (COTS) Product Lifecycle Management (PLM) systems have been introduced by companies to facilitate their new product development process to shorten the product time to market, reduce the product development cost, and meet the dynamic demands of customers. However, PLM implementation is not an easy job and some of the attempted projects failed. A common problem encountered in adopting PLM packages has been the issue of misfits, i.e., the gaps between the specifications offered by a PLM package and those required by the adopting organization, which easily causes the project to fail. Current approaches for the ex-ante analysis of PLM misfits are extremely limited. This paper develops a methodology grounded in the extended cognitive fit theory for the misfit analysis. This approach can assist in identifying and representing consistent set of information for functions and workflow processes across business requirements and the PLM package. Particularly, Petri nets that are of graphical representations and easy to understand are employed to model the function-embedded workflow process. A case study is presented to examine the feasibility of this approach. We conclude that with our methodology, PLM analysts or adopting organizations can systematically identify potential misfits and the degree of misfit between the business requirements and PLM packages in an ex-ante analysis to mitigate the risks in PLM implementations

Learning to Ask: Question-based Sequential Bayesian Product Search

Product search is generally recognized as the first and foremost stage of online shopping and thus significant for users and retailers of e-commerce. Most of the traditional retrieval methods use some similarity functions to match the user's query and the document that describes a product, either directly or in a latent vector space. However, user queries are often too general to capture the minute details of the specific product that a user is looking for. In this paper, we propose a novel interactive method to effectively locate the best matching product. The method is based on the assumption that there is a set of candidate questions for each product to be asked. In this work, we instantiate this candidate set by making the hypothesis that products can be discriminated by the entities that appear in the documents associated with them. We propose a Question-based Sequential Bayesian Product Search method, QSBPS, which directly queries users on the expected presence of entities in the relevant product documents. The method learns the product relevance as well as the reward of the potential questions to be asked to the user by being trained on the search history and purchase behavior of a specific user together with that of other users. The experimental results show that the proposed method can greatly improve the performance of product search compared to the state-of-the-art baselines.Comment: This paper is accepted by CIKM 201

Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Renal impairment in a rural African antiretroviral programme

Background: There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods: (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results: (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion: In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited

A Novel Design of Grooved Fibers for Fiber-Optic Localized Plasmon Resonance Biosensors

Bio-molecular recognition is detected by the unique optical properties of self-assembled gold nanoparticles on the unclad portions of an optical fiber whose surfaces have been modified with a receptor. To enhance the performance of the sensing platform, the sensing element is integrated with a microfluidic chip to reduce sample and reagent volume, to shorten response time and analysis time, as well as to increase sensitivity. The main purpose of the present study is to design grooves on the optical fiber for the FO-LPR microfluidic chip and investigate the effect of the groove geometry on the biochemical binding kinetics through simulations. The optical fiber is designed and termed as U-type or D-type based on the shape of the grooves. The numerical results indicate that the design of the D-type fiber exhibits efficient performance on biochemical binding. The grooves designed on the optical fiber also induce chaotic advection to enhance the mixing in the microchannel. The mixing patterns indicate that D-type grooves enhance the mixing more effectively than U-type grooves. D-type fiber with six grooves is the optimum design according to the numerical results. The experimental results show that the D-type fiber could sustain larger elongation than the U-type fiber. Furthermore, this study successfully demonstrates the feasibility of fabricating the grooved optical fibers by the femtosecond laser, and making a transmission-based FO-LPR probe for chemical sensing. The sensor resolution of the sensor implementing the D-type fiber modified by gold nanoparticles was 4.1 × 10−7 RIU, which is much more sensitive than that of U-type optical fiber (1.8 × 10−3 RIU)

Infection with human immunodeficiency virus in the pittsburgh transplant population: A study of 583 donors and 1043 recipients, 1981-1986

We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV- 1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P<0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1. © 1989 by The Williams and Wilkins Co