Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10 5 cells) than those volumes detectable clinically (10 7 -10 8 cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients.
Objectives. Systematic review of point of care (POC) diagnostic tests for sexually transmitted infections: Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Methods. Literature search on PubMed for articles from January 2010 to August 2015, including original research in English on POC diagnostics for sexually transmitted CT, NG, and/or TV. Results. We identified 33 publications with original research on POC diagnostics for CT, NG, and/or TV. Thirteen articles evaluated test performance, yielding at least one test for each infection with sensitivity and specificity ≥90%. Each infection also had currently available tests with sensitivities <60%. Three articles analyzed cost effectiveness, and five publications discussed acceptability and feasibility. POC testing was acceptable to both providers and patients and was also demonstrated to be cost effective. Fourteen proof of concept articles introduced new tests. Conclusions. Highly sensitive and specific POC tests are available for CT, NG, and TV, but improvement is possible. Future research should focus on acceptability, feasibility, and cost of POC testing. While pregnant women specifically have not been studied, the results available in nonpregnant populations are encouraging for the ability to test and treat women in antenatal care to prevent adverse pregnancy and neonatal outcomes.
Objectives The World Health Organization called for the elimination of maternal-to-child transmission (MTCT) of HIV and syphilis, a harmonized approach for the improvement of health outcomes for mothers and children. Testing early in pregnancy, treating seropositive pregnant women, and preventing syphilis re-infection can prevent MTCT of HIV and syphilis. We assessed the health and economic outcomes of a dual testing strategy in a simulated cohort of 100,000 antenatal care patients in Malawi. Methods We compared four screening algorithms: (1) HIV rapid test only, (2) dual HIV and syphilis rapid tests, (3) single rapid tests for HIV and syphilis, and (4) HIV rapid and syphilis laboratory tests. We calculated the expected number of adverse pregnancy outcomes, the expected costs, and the expected newborn disability adjusted life years (DALYs) for each screening algorithm. The estimated costs and DALYs for each screening algorithm were assessed from a societal perspective using Markov progression models. Additionally, we conducted a Monte Carlo multi-way sensitivity analysis, allowing for ranges of inputs. Results Our cohort decision model predicted the lowest number of adverse pregnancy outcomes in the dual HIV and syphilis rapid test strategy. Additionally, from the societal perspective, the costs of prevention and care using a dual HIV and syphilis rapid testing strategy was both the least costly ($226.92 per pregnancy) and resulted in the fewest DALYs (116,639) per 100,000 pregnancies. In the Monte Carlo simulation the dual HIV and syphilis algorithm was always cost saving and almost always reduced disability adjusted life years (DALYs) compared to HIV testing alone. Conclusion The results of the cost-effectiveness analysis showed that a dual HIV and syphilis test was cost saving compared to all other screening strategies. Adding dual rapid testing to the existing prevention of mother-to-child HIV transmission programs in Malawi and similar countries is likely to be advantageous.
BACKGROUND Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. STI prevalence and its association with HIV mother-to-child transmission (MTCT) were evaluated in a sub-study analysis from a randomized, multi-center clinical trial. METHODOLOGY Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction (PCR) testing for the detection of CT and NG (Xpert® CT/NG, Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA PCR at 3 months. RESULTS Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission) the lowest transmission rate occurred among infants born to CT and NG uninfected mothers (8.1%) as compared to those infected with only CT (10.7%) and both CT and NG (14.3%), (p = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (OR 1.47, 95% CI 0.9–2.3, p=0.09). CONCLUSION This cohort of HIV-infected pregnant women are at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high risk cohort of HIV-infected women.
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